A phase II study of docetaxel and gemcitabine in the treatment of recurrent ovarian, peritoneal, and fallopian tube cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15006-15006
Author(s):  
M. S. Shahin ◽  
P. Hanjani ◽  
S. Nolte
Keyword(s):  
Fallopian Tube ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Hematologic Toxicity ◽  
Fallopian Tube Cancer ◽  
Overall Response ◽  
Platinum Sensitive ◽  
Significant Difference ◽  
Grade 3

15006 Background: The aim of this trial was to investigate the efficacy and toxicity of weekly combination of docetaxel (D) and gemcitabine (G) in the management of recurrent ovarian, peritoneal, or fallopian tube cancer. Methods: D (30 mg/m2) was given as a one-hour IV infusion followed by G (650 mg/m2) as a 30 minute IV infusion on Day 1, 8 & 15 of a 28-day cycle. Results: Thirty pts were enrolled. Mean age was 67.4 (range 47–85). Twelve (40%) pts had Platinum sensitive disease, and 18 (60%) had Platinum resistant disease. One hundred eighteen cycles were evaluable for toxicity. The mean number of cycles was 4 (range 1–7). Twenty-six (22%) of the cycles were incomplete due to toxicity (day # 15 not given in 25 of the incomplete cycles). Dose delay was observed in 4 (13.3%) pts, and a one-dose level reduction was required in 11 (36.7%) pts. Hematologic toxicity included grade 3 neutropenia in 13 (11%) cycles, grade 3 thrombocytopenia in 11 (9.3%) cycles. No grade 4 neutropenia, thrombocytopenia or neutropenic fever was encountered. Bone marrow support with erythropoiten (36.6% pts), and filgrastim (13.3% pts) were utilized. Blood transfusions were given in 10 (8.5%) cycles. Elevated LFT grade 1/2 was seen in 7 (23.3%) pts and 3 (10%) pts, respectively. Nonhematologic grade 3 toxicites occurred in 4 pts (including one seizure). Mean follow-up interval was 19.6 months (mos) (range 1–36.6). To date, 14 (46.6%) pts are alive with disease, and 16 (53.4%) have died of disease. The overall response rate was 32% (1 CR and 8 PR in 28 evaluable pts). Ten pts (33.3%) had SD and 5 had ID. Median progression-free interval (PFI) was 3.8 mos (95% CI: 1.65–5.97). Overall survival was 19.6 mos (95% CI: 14.23–24.96), and no significant differences in PFI and survival between the Platinum-sensitive and resistant pts (P = 0.5, P = 0.08, respectively). Conclusions: Weekly docetaxel plus gemcitabine is an active and tolerable regimen with minimal toxicity in this older population of pts (9 ≥ 80 years of age). No significant difference in response between Platinum sensitive and resistant pts was observed. Overall response rate appears to be better than single agent regimens currently available. Elimination of the third week of treatment may not affect efficacy and will be more acceptable to pts with less toxicity. No significant financial relationships to disclose.

SDX-105 Demonstrates a High Response Rate as a Single-Agent with Acceptable Safety in Rituximab-Refractory, Relpased Indolent or Transformed Non-Hodgkin’s Lymphoma (NHL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2480-2480 ◽  
Author(s):  
Jonathan Friedberg ◽  
Philip Cohen ◽  
Robert O. Kerr ◽  
K. Sue Robinson ◽  
Andres Forero-Torres ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dose Reduction ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Mitotic Catastrophe ◽  
Hematologic Toxicity ◽  
Overall Response ◽  
Cell Death Pathway ◽  
Grade 3

Abstract SDX-105 (Treanda™, Bendamustine HCl) is an alkylating agent that may exert its anti-tumor activity via mitotic catastrophe, an apoptosis-independent cell-death pathway, as well as, through apoptosis. Its cytotoxic potency is unattenuated in chemotherapy-resistant lymphoma cell lines. We initiated a multi-center Phase II trial to investigate the safety and efficacy of SDX-105 in patients with rituximab-refractory, relapsed indolent or transformed B cell NHL. Patients must have pathologically-confirmed disease that has been demonstrated to be rituximab-refractory (no response or progression within 6 months) or must be intolerant of rituximab. Other requirements include measurable disease, adequate renal, hepatic and bone marrow function (ANC ≥1K/mm3, platelet ≥ 100K/mm3, except in cases of >50% NHL in bone marrow), up to 3 prior chemotherapies, and no prior allogeneic transplant. Patients receive SDX-105, 120 mg/m2 IV over 30–60 min, days 1 and 2, every 21 days. Grade 4 hematologic toxicity during a cycle results in dose reduction for subsequent cycles (to 90 mg/m2 and then to 60 mg/m2). Patients achieving stable disease or better after 6 cycles may receive up to 6 more cycles. 49 patients have been accrued to date with data available on the first 15 patients. The median age is 69 yrs (range 47–84), 47% male, median 6 yrs since diagnosis with NHL. Histologies: 10 follicular (6 Grade 1, 3 Grade 2, 1 Grade 3), 2 SLL, 1 marginal zone and 2 transformed NHL. Other features include: 93% Stage III/IV, 20% with B symptoms, 87% with extranodal disease, median 2 prior chemotherapies with 40% not responding to last chemotherapy. 4 patients have required dose reduction to 90 mg/m2 and 2 patients have withdrawn prior to completing 6 cycles due to treatment-associated toxicity. The current overall response rate (ORR) based upon best response in the intent-to-treat population is 80% (CR/CRu 20%, PR 60%). Overall 73% of patients experienced a related non-hematologic adverse event (AE), of which 20% were Grade 3 and 0% Grade 4. The most frequent AEs were nausea (40%), vomiting (27%), fatigue (33%), anorexia (20%), and constipation (20%). Alopecia was not observed. Grade 3 or 4 hematologic toxicity was seen in 53% (neutropenia), 20% (thrombocytopenia), and 13% (anemia) of patients. 4 patients experienced serious AEs, including 1 patient with baseline renal insufficiency who died on study from renal failure and pulmonary edema; other events include admissions for fever and anemia, urinary tract infection, and dehydration. Based upon these preliminary findings, SDX-105 demonstrates a high overall response rate with acceptable hematologic toxicity and modest non-hematologic toxicity in a relapsed lymphoma patient population, many of whom are refractory to rituximab-chemotherapy combinations. An additional study evaluating the combination of SDX-105 and rituximab in patients with relapsed indolent NHL who are rituximab-sensitive is also ongoing.

A Phase I/II Study of Bortezomib and Low Dose Intravenous Melphalan (BM) for Relapsed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2555-2555 ◽  
Author(s):  
Rakesh Popat ◽  
Heather E. Oakervee ◽  
Nicola Foot ◽  
Samir Agrawal ◽  
Patricia Smith ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Progressive Disease ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Median Number ◽  
Overall Response ◽  
Grade 3 ◽  
Number Of Cycles

Abstract Background: Bortezomib as a single agent has known efficacy in the treatment of relapsed multiple myeloma. The overall response rate (CR+PR+MR) was 35% in the SUMMIT study and 46% in the APEX study. In-vitro studies including our own have demonstrated potent synergy with other chemotherapeutic agents such as melphalan. It therefore follows that responses to bortezomib may be further improved by the combination of such drugs. Aims: The primary objectives of this Phase I/II study was to assess the safety, tolerability and response rates in patients with relapsed multiple myeloma; secondary objectives being time to progression (TTP) and overall surival (OS). Methods: This was a multi-centre, non-randomised trial for patients with relapsed myeloma. Patients received bortezomib 1.3mg/m2 on days 1,4,8 and 11 of each 28 day cycle with melphalan on day 2 at increasing dose levels. This was initially at 10mg/m2, but due to cytopenias subsequently at 2.5 and 5mg/m2 (levels 1a, 1 and 2) and we plan to escalate to 7.5mg/m2. Up to 8 cycles were given with dexamethasone added for stable or progressive disease after 4 or 2 cycles respectively. Responses were determined by EBMT criteria. Results: To date, 18 patients have been enrolled (12 male 6 female; median age 60 [range 44–73]; median number of prior therapies 3 [range 1–5] of which 17 have had at least one autologous stem cell procedure with high dose melphalan; 10 prior thalidomide and 2 prior bortezomib). 12 patients received melphalan at 10mg/m2 but due to unacceptable delays predominantly due to thrombocytopaenia, subsequent treatment levels commenced at 2.5mg/m2. The median number of cycles completed thus far is 4 (range 0–8) and of the 16 evaluable, the overall response rate (CR+PR+MR) across all treatment levels was 50% rising to 75% following the addition of dexamethasone as per protocol. At level 1a (melphalan 10mg/m2 ,N=12, median number of cycles completed =5) the best responses (with dexamethasone as indicated) were: 1CR, 1 VGPR, 5 PR, 2 MR; at level 1 (melphalan 2.5mg/m2, N=4) 1 PR, 2 MR (after 2 cycles only). The median time to any response was 1 cycle (range 1–3 ). Three patients have progressive disease, but the median TTP and OS have not yet been reached (median follow-up 3 months). Non-haematological toxicities have been modest with 7 SAEs reported of which only 1 was possibly drug related (myocardial infarction), and 4 episodes of Grade 3 neuropathy (2 resulting in study withdrawal). The commonest grade 3–4 haematological toxicity was thrombocytopaenia (N=10) complicated by bleeding in one patient, followed by neutropenia (N=6). Summary: The combination of bortezomib and intravenous melphalan can be given safely to patients with relapsed multiple myeloma and dose escalation is ongoing. Myelosupression was the commonest grade 3–4 adverse event. A response rate of 50% was seen, which was further improved to 75% with the addition of dexamethasone. This combination may therefore result in higher responses than single agent bortezomib in heavily pretreated patients.

Phase II study of topotecan and carboplatin in the treatment of platinum-sensitive recurrent ovarian and peritoneal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15001-15001
Author(s):  
P. Hanjani ◽  
M. S. Shahin
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Hematologic Toxicity ◽  
Peritoneal Cancer ◽  
Platinum Sensitive ◽  
Free Interval ◽  
Alive With Disease ◽  
Grade 3

15001 Background: The aim of this trial was to investigate the efficacy and toxicity of the combination of Topotecan (T) and Carboplatinum (C) in the management of recurrent platinum sensitive ovarian and peritoneal cancer. Methods: T (1 mg/m2) was given as a 30-minute infusion daily × 3 days and C (AUC 5) was given as a 30-minute infusion following T on day 3 on a 21-day cycle. Results: Thirty patients (pts) were enrolled and all pts were evaluable for response and toxicity. Mean age was 63.2 (range = 44–84). One hundred eighty five cycles (mean/pt = 6, range 2–10) were evaluable for toxicity. Dose escalation (T = 1.25 mg/m2) was possible in 25 (83.3%) pts. Hematologic toxicity grade 3 and 4 neutropenia was seen in 60 (32.4%) and 10 (5.4%) cycles, respectively. Grade 3 thrombocytopenia was encountered in 24 (13%) cycles. Grade 3 Hgb was observed in 4 (2.2%) cycles. No grade 4 thrombocytopenia/Hgb or neutropenic fever was encountered. Blood transfusions were required in 9 (4.9%) cycles. Bone marrow support with erythropoiten (40% pts), and filgrastim (43.3% pts) were utilized. No neuropathy > grade 1 was encountered. Fourteen pts (46.6%) pts had a hypersensitivity reaction to C and successful desensitization was carried out in 8 (57.1%). Mean follow-up interval was 16.9 months (mos) (Range 1.7–43). To date, 6 (20%) pts are alive without disease, 16 (53.3%) are alive with disease, and 8 (26.7) have died of disease. The overall response rate was 83.3% (5 CR and 20 PR). Five (16.6%) pts had SD. Median progression-free interval was 8.2 mos. Overall mean survival for the cohort was 31.2 mos (95% CI: 24.47–37.71). Conclusions: Given the ICON-4 data, supporting combination therapy in recurrent platinum-sensitive patients, this regimen provides an effective and tolerable alternative to Taxane-platinum combination with no significant neuropathy. This regimen is especially attractive in patients who have significant residual neuropathy after initial treatment. Carboplatinum desensitization was feasible in previously pre-treated patients. No significant financial relationships to disclose.

Cyclophosphamide Remains An Important Component of Treatment in CLL Patients Receiving Pentostatin and Rituximab Based Chemoimmunotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 43-43 ◽  
Author(s):  
Neil E. Kay ◽  
Wenting Wu ◽  
John C. Byrd ◽  
Brian Kabat ◽  
Diane F. Jelinek ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Patient Characteristics ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Overall Response ◽  
Grade 3 ◽  
Ecog Ps ◽  
Experienced Grade

Abstract BACKGROUND: We have previously studied and reported that the combination of pentostatin (P, 2 mg/m2), cyclophosphamide (C 600 mg/m2) and rituximab (R 375 mg/m2) in previously untreated CLL is highly effective with an overall response (OR) rate of over 90% and a complete response rate (CR) of 41% (Blood109:405–411, 2007). We also found that this regimen can be effective even in older patients (>70 y), those with elevated beta-2 microglobulin levels, and patients with mildly reduced creatinine clearances (Cancer. 109:2291–2298, 2007). To determine whether similar benefit could be achieved without inclusion of an alkylating agent, we conducted a follow-up trial testing pentostatin and rituximab without cyclophosphamide and employing a higher pentostatin dose (4 mg/m2). METHODS: Eligible pts had documentation of active CLL by standard NCI-WG criteria, and were previously untreated. Treatment schema consisted of 6 cycles of pentostatin (4 mg/m2) and rituximab given every 21 days. Pentostatin was given on the first day of each cycle following infusion of rituximab. Rituximab was given at 100mg/m2 IV at day 1, then 375 mg/m2 IV on days 3 and 5 of the first treatment cycle. During cycles 2 to 6, Rituximab was given at 375 mg/m2 as a single IV infusion day 1 of week 4, 7, 10, 13 and 16. All patients were staged two months after completion of the 6 cycles of PR using the NCI-WG criteria. PATIENT CHARACTERISTICS: Overall, 33 patients were enrolled at Mayo Clinic and Ohio State University between July 2005 and February 2008. All 33 were eligible: 82% male, median age 65 (range: 45–81), with 9 (27%) being 70 years or older. 76% had a baseline ECOG PS of 0, and the rest were ECOG PS 1. Overall, 36% of patients had intermediate Rai risk (stage I–II) and 63% high Rai risk (stage 3–4) disease. Prognostic testing revealed that 36% were CD38+, 50% were Zap-70 +, and 39% had an unmutated IgVh status. Chromosome analysis by FISH found that 99% had detectable FISH panel defect, including 61%, 27% and 3% of patients with 1, 2, or 3 FISH detects, respectively. RESULTS: 28 of 33 patients (85%) completed therapy. While on treatment, 6 pts (18%) had a dose held or modified with 4 of these delays due to hematologic AE. For adverse events deemed at least possibly related to treatment, 4 (12%) pts experienced grade 3+ hematologic toxicity and 5 (15%) experienced grade 3+ non-hematologic toxicity. Out of all 33 enrolled patients, the overall response rate was 79% with 10 CR, 6 nPR, and 10 PR. At the time of this analysis, 29/33 patients are still alive with a median follow-up time of 14 months on surviving patients. To date 17/33 (52%) of patients have progressed with an estimated median time to progression of 12 months (95% CI: 8.5–21 months). 13/26 responders have progressed. Median duration of response is 12.5 months ((95% CI: 11–21 months). Finally, since eligibility were nearly identical and enrollment accrued at the same two academic centers, we compared the patient characteristics, response rates, and PFS of the 33 patients treated with PR to the 64 patients previously treated on our PCR trial. Patients in the two studies were generally similar with respect to demographic and prognostic characteristics, although patients in the PR trial had higher WBC and were less likely to be IgVH unmutated (Table). Although the differences in ORR and CR rate were not significantly different, the PFS appeared to be inferior in patients treated with PR as compared to PCR (12 months vs. 31 months; p=0.003). CONCLUSION: Although the PR regimen achieves a high OR response rate, the PFS appears inferior to PCR therapy. These findings suggest that increasing the purine nucleoside analogue dose does not eliminate the need to include cyclophosphamide in chemoimmunotherapy for patients with CLL. PCR Trial N=64 PR Trial N=33 P value Age, median(range) 63 years (38–80) 65 years (45–81) 0.34 ≥70 years(%) 28% 27% Male 77% 82% 0.61 Rai stage 0 5% 0 0.46 Rai stage I–II 42% 36% Rai stage III–IV 53% 64% White Cell Count, median(range) 79 × 109/L (11–519) 127 × 109/L (8–430) 0.04 <50 × 109/L 36% 28% 50–149 × 109/L 44% 25% >150 × 109/L 20% 47% Serum B2-microglobulin, median(range) 3.97 (1.8–13.5) 3.80 (2.0–8.2) 0.81 >2 × Upper Limit Normal(%) 57% 58% CD38 Positive 34% 36% 1.00 ZAP-70 Positive 36% 50% 0.26 IgVH Unmutated 71% 39% 0.004 FISH Normal, 11% 9% 13q- 35% 42% +12 21% 24% 6q- 2% 0 11q- 22% 18% 17p- 6% 3% other 3% 3% Overall Response Rate 91% 79% 0.12 Complete Response Rate 41% 30% 0.38 Median PFS 31 months 12 months 0.003

Phase II study of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone (DEX), and lenalidomide (LEN) in patients with newly diagnosed (ND) multiple myeloma (MM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8518-8518
Author(s):  
R. Baz ◽  
M. A. Hussein ◽  
D. Sullivan ◽  
J. Raychaudhuri ◽  
L. Ochoa ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
High Dose ◽  
Hematologic Toxicity ◽  
High Dose Therapy ◽  
Overall Response ◽  
Dose Therapy ◽  
Grade 3

8518 Background: We previously reported the results of a phase I/II trial of PLD, low dose DEX and LEN in patients with relapsed and refractory MM in which the MTD of LEN was 10 mg (for 21 of 28 days) and the overall response rate was 75% with 29% of patients achieving nCR or better (Ann Oncol 2006). Accordingly we evaluated this regimen in ND MM. Methods: We hypothesized that patients with ND MM would tolerate this combination better. Accordingly, patients received PLD (40 mg/m2 on day 1), DEX (40 mg on days 1–4) and LEN (25 mg Days 1–21) every 28 days (for 2 cycles beyond best response: 4–8 cycles). Prophylactic low dose aspirin, acyclovir and fluoroquinolone were recommended. Patients not eligible or not wishing to proceed with high dose therapy continued on the tolerated dose of LEN and DEX until disease progression or unacceptable toxicity. Results: Between 2/2008 and 8/2008, 31 of a planned 60 patients were enrolled. 2 patients were screen failures and are not included in subsequent analysis. The mean age was 64 years (41–82) and 58% were males. The median β2microglobulin was 2.8 mg/dL (34% had β2m>3.5). Using the modified SWOG criteria and after a median of 4 cycles of therapy, the overall response rate was 80% with 40% VGPR and better. Two patients had stable disease and 3 patients had progressive disease. Grade 3/4 hematologic toxicity was as follows: neutropenia (48%), anemia (10%), thrombocytopenia (7%). Grade 3/4 non-hematologic toxicity included: Fatigue (21%), infections and febrile neutropenia (20%, only 1 patient with febrile neutropenia), venous thromboembolic events (10%). 14 patients went off study including 8 patients to proceed with high dose therapy. Conclusions: The combination of PLD, LEN and DEX is an active regimen in patients with ND MM. Due to the unexpected higher rates of neutropenia and fatigue, the dose of PLD will be decreased to 30 mg/m2 every 28 days. Updated results will be presented at the time of the meeting. [Table: see text]

Phase II Study of Lenalidomide in Combination with Rituximab for Patients with CD5+/CD20+ Hematologic Malignancies Who Relapse or Progress After Rituximab. Interim Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2376-2376
Author(s):  
Marays Veliz ◽  
Ricardo Santana ◽  
Jeffrey E Lancet ◽  
Rami S. Komrokji ◽  
Mohamed A Kharfan-Dabaja ◽  
...  
Keyword(s):  
Phase Ii ◽  
Poor Prognosis ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Combination Regimen ◽  
Duration Of Treatment ◽  
Bone Marrow Biopsies ◽  
Overall Response ◽  
Grade 3

Abstract Abstract 2376 Poster Board II-353 Background: Patients with relapsed or refractory CLL/SLL and patients with mantle cell lymphoma (McL) have a poor prognosis. Overall response rate (ORR) to salvage therapy for refractory patients is approximately 10-30%, and survival benefit with current treatment approaches is limited. Phase II studies of single agent lenalidomide in patients with relapsed or refractory CLL revealed an ORR of 32-58% (7-17% CR), depending on treatment dose, scheduled used and duration of treatment with lenalidomide. In patients with refractory or relapsed McL, lenalidomide treatment resulted in an ORR of 53% (CR 20%, PR 33%), and a 14-month median duration of response (Habermann et al 2009). Recent in vitro studies have shown that lenalidomide enhances the rituximab-induced killing of NHL cell lines and B-CLL cells via ADCC by restoring the defective T-cell and NK-cell mediated ability to form immune synapses to exert tumor cell cytotoxicity. Methods: Patients with relapsed or refractory CLL/SLL or McL received oral lenalidomide via dose escalation as follows, 2.5 mg on days 1-7, 5mg on day 8-14 and 10mg on day 15-21 followed by 7 days of rest in 28-day cycle; for cycle 2 and beyond 20mg was given on day 1-21 on a 28 day cycle. Rituximab was dosed at 375mg/m2 IV weekly for 4 weeks starting on day 15 of cycle 1. Treatment was continued until disease progression or toxicity. All patients were given allopurinol 300mg orally twice per day starting 3 days prior to first dose of lenalidomide. CT scans, and bone marrow biopsies were done every 2 months to assess for response. Primary objectives were overall response rate (CR+PR) and safety and tolerability of the combination regimen. Results: 17 patients were enrolled on study (13 patients with CLL/SLL and 4 patients with McL). Median number of prior chemotherapies was 3 (range 1-5). Median age was 64 years (range 42-80). Among patients with CLL, the most common cytogenetic abnormalities were trisomy 12 (isolated n=3, associated with other abnormalities n=4), del11q (isolated n=1, with others n=3), isolated del13q (n=1), complex cytogenetics with 3 or more abnormalities (n=4 including 1 patient with del 17p). Responses were assessed every 2 months after initiation of therapy. Response rate for 13 evaluable patients (10 with CLL and 3 with McL) relative to months on treatment with lenalidomide are summarized in the table. Although all responses were PR, the rate of PR improved with continued therapy suggesting increased responses with a longer duration of treatment with lenalidomide. Currently, 7 patients are still receiving active treatment on study, all with CLL (3 achieved a PR and 4 have SD). Of the 4 patients with McL enrolled on study, 1 achieved a PR after 2 months of therapy; 1 achieved SD after 2 months of therapy with a sustained SD after 6 months; 1 patient achieved SD after 2 months, but progressed after 6 months on treatment. The regimen was well tolerated. Most common (>5%) toxicities include neutropenia (35% grade 3, 6% grade 4), fatigue (17% grade 1-2, 6% grade 3), tumor flare (12% grade 2, 12% grade 3), acute renal insufficiency (6% grade 1, 12% grade 3), rituximab related infusion reactions (6% grade 2, 6% grade 3), flu-like symptoms (6% grade 2, 6% grade 3), venous thromboembolic disease (6% grade 2, 6% grade 3), infections (11% including 1 patient with fatal endocarditis), and hypercalcemia (11% grade 4). Correlative studies are ongoing. Conclusions: The combination of lenalidomide with Rituximab is a promising combination regimen in CLL patients with very poor prognosis who have undergone multiple lines of therapy. This treatment combination appears tolerable with observed events consistent with the use of these two agents in other studies. Further investigation is warranted, possibly in the front line setting and in combination with other agents. Disclosures: Lancet: Celgene: Research Funding.

A Phase II Study of Carfilzomib, Pegylated Liposomal Doxorubicin, and Dexamethasone for Relapsed or Refractory Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3329-3329 ◽  
Author(s):  
Mark A Fiala ◽  
Jesse Keller ◽  
Jeevan Sekhar ◽  
Connie Ceriotti ◽  
Camille N. Abboud ◽  
...  
Keyword(s):  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
Pegylated Liposomal Doxorubicin ◽  
Median Number ◽  
Hematologic Toxicity ◽  
Event Free Survival ◽  
Free Survival ◽  
Overall Response ◽  
Grade 3

Abstract Background: We previously reported on a phase I dose escalation trial of CDD [carfilzomib (CFZ), pegylated liposomal doxorubicin (PLD), and dexamethasone (DEX)] (Keller, et, al, ASH 2014 Abstract 4731). The combination was well tolerated and an MTD was not reached despite administering the currently approved single-agent doses. In the maximum dose level tested, the overall response rate (ORR) was 72% (5/7) in a heavily pre-treated population. Based on the promising results of the phase I study we conducted a phase II expansion to further evaluate the efficacy of the regimen. Patient/Methods: Patients with RRMM after ≥ 1 lines of therapy, with measureable disease, and good performance status, organ function and hematological reserve were eligible. Prior CFZ or PLD/doxorubicin exposure was permitted. CFZ was given on days 1, 2, 8, 9, 15 and 16 in 28 day cycles at a dose of 56mg/m2, PLD on day 8 at a dose of 30mg/m2,DEX on days 1, 2, 8, 9, 15 and 16 at a dose of 20mg. Following 6 cycles of combination therapy, PLD was discontinued and patients were treated with maintenance CFZ and DEX (once weekly). Response was assessed per IMWG criteria. Overall response rate (ORR) was defined as partial response (PR) or better, event-free survival as the interval from start of therapy to discontinuation. Results: Twenty-three patients were enrolled from April 2014-Mar 2016. Median age was 63 years (range 27-70) and 52% were male. Ten patients were ISS stage 1, 6 were stage 2, and 7 were stage 3. By mSMART criteria, 1 patient was high risk and 5 were intermediate risk. Ten patients were IgG Kappa subtype; 4 had IgG Lambda subtype, 2 had IgA Kappa subtype, 2 had IgA Lambda subtype, 3 kappa light chain, and 2 lambda light chain. The median number of prior therapies was 2 (range 1-13); median time from diagnosis to start of protocol was 40 months (range 8-200). All had prior exposure to lenalidomide; 91% to bortezomib; 9% to PLD or doxorubicin; 9% to CFZ; 96% had undergone autologous transplantation. The overall response rate was 83% with 48% achieving a complete or very good partial response. The median number of cycles was 11; the median estimated event-free survival was 7.4 months at a median follow-up of 10.6 months. Five patients discontinued due to disease progression, 7 due to toxicity, 1 to proceed to a second transplant, and 10 remain on treatment at time of submission. Individual patient responses are summarized in Table 1. Grade 3/4 non-hematologic toxicity was uncommon but included: infections (11), hypertension (4), RPLS (1), and MI (1). Grade 3/4 hematologic toxicity included: thrombocytopenia (11), anemia (8), neutropenia (7), TTP (1), and hemolysis (1). Conclusion: CDD is well tolerated and efficacious in relapsed or refractory MM. The estimated ORR of the combination is 83% (95% CI 67%-98%) a notable increase compared to standard dose CFZ and DEX. Disclosures Abboud: Gerson and Lehman Group: Consultancy; Baxalta: Honoraria; Takeda: Honoraria; Novartis: Research Funding; Seattle Genetics: Research Funding; Alexion: Honoraria; Cardinal: Honoraria; Teva: Research Funding, Speakers Bureau; Pharmacyclics: Honoraria; Pfizer: Research Funding; Merck: Research Funding. DiPersio:Incyte Corporation: Research Funding. Vij:Amgen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy; Shire: Consultancy; Jazz: Consultancy; Karyopharma: Consultancy; Novartis: Consultancy.

Ofatumumab in combination with high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7124-7124
Author(s):  
Januario E. Castro ◽  
Michael Y. Choi ◽  
Tomas Carvajal ◽  
Hongying Li ◽  
Danelle Frances James ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Lymphocytic Leukemia ◽  
P Value ◽  
High Dose ◽  
Free Survival ◽  
Overall Response ◽  
Coronary Syndrome ◽  
Grade 3

7124 Background: We performed a phase II, single-arm, clinical trial evaluating ofatumumab in combination with HDMP for the treatment of patients with relapsed or refractory CLL. Methods: Patients received ofatumumab at the dose of 1,000 mg weekly (half the conventional dose) for 12 weeks, without monthly maintenance doses. The HDMP dose was 1,000 mg/m2for 3 days of each of 3 monthly cycles. Prophylactic medications included acyclovir, bactrim, fluconazole, and allopurinol. Results: 21 patients were enrolled at a single center. The median age was 63 years (range 46–76). The median number of prior therapies was 3. 24% had unfavorable cytogenetics (Del 17p or Del 11q) and 76% had CLL cells that expressed unmutated IgVH genes or high levels of ZAP-70. 24% were fludarabine-refractory. Treatment was well tolerated. The majority of adverse events were grade 1 or 2, including insomnia, anxiety, fatigue, and infusion reactions. There were no grade 4 toxicities.19% of patients had grade 3 neutropenia, and 5% had grade 3 thrombocytopenia. Other grade 3 toxicities were hyperglycemia (71%), non-melanoma skin cancer and other skin lesions (19%), as well as acute coronary syndrome, atrial fibrillation, renal calculi, pneumonia, and hypocalcemia (1 patient each). Responses were assessed two months after completion of therapy. The overall response rate was 81% (17/21) with 5% CR (1/21), 10% nodular PR (2/21), 67% PR (14/21), 14% SD (3/21), and 5% PD. The median follow-up time was 12 months (range 5-23). The median progression-free survival (PFS) time was 9.1 months (95%CI: 7.5-NA) and the median treatment-free survival (TFS) was 11.5 months (95%CI: 10.0-NA). Patients with Del 17p or Del 11q had a significantly lower overall response rate (p-value <0.001, fisher’s exact test). Conclusions: The combination of HDMP and ofatumumab is an effective, tolerable, non-myelosuppressive treatment regimen. We observed a higher ORR and longer PFS than those previously reported with single agent mAb. This regimen may be useful for patients who are unable to tolerate more aggressive, myelosuppressive therapies, or have not responded to other treatments.

PECULIAR study: Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 301-301
Author(s):  
Jae-Lyun Lee ◽  
Se-Hoon Lee ◽  
Yoon Ji Choi ◽  
Jin-Hee Ahn ◽  
Cheryn Song ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Urothelial Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Study Phase ◽  
Overall Response ◽  
Advanced Urothelial Cancer ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

301 Background: Pemetrexed has demonstrated a favorable response with minimal toxicity when used as single agent as first-line and second-line treatment for advanced urothelial carcinoma. The safety and tolerability of pemetrexed plus cisplatin combination has been widely recognized in malignant mesothelioma. This trial was performed to evaluate the efficacy and safety of pemetrexed plus cisplatin in advanced urothelial carcinoma. Methods: Eligible criteria included chemotherapy-naïve advanced urothelial carcinoma, ECOG PS 0-2 and measurable disease. Pemetrexed 500mg/m2 on day 1 with cisplatin 70 mg/m2on day 1 were administered every 3 weeks til disease progression or a maximal of 8 cycles. Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicities. Response was evaluated every 6 weeks according to the RECIST criteria v.1.0 and toxicities were assessed with NCI CTCAE v.3.0. Results: A total of 42 patients were enrolled and 2 patients were excluded because of different histology and concomitant malignancy. At the time of this analysis, 36 patients (median age 66 years, ECOG 0-1 100%, visceral metastasis 50.0%, recurrent disease 61.1%) were evaluable; 6 patients were too early to assess. Twenty four partial responses for an overall response rate of 66.7% [95% confidence interval (CI) 50.3-79.9%] were documented. Six patients had stable disease. The median PFS was estimated to be 6.9 months [95% CI 6.2-7.7 months]. The median OS was 16.3 months [95% CI 12.9-19.7 months]. The most common grade 3 or 4 toxicities were neutropenia in 33.3% of patients. No one experienced febrile neutropenia. Other grade 3 or 4 hematological and non-hematological toxicities were rarely observed (thrombocytopenia 6%, anemia 6%, transaminitis 6%, nausea 3%, anorexia 3%, edema 3%, dyspnea 3%). Conclusions: The combination of pemetrexed and cisplatin is very active, with an overall response rate of 66.7% and well tolerated in patients with advanced urothelial cancer. The final mature results will be presented in the meeting. Clinical trial information: NCT01490437.

Combination of trastuzumab, pertuzumab and docetaxel in patients with advanced non-small cell lung cancer (NSCLC) harboring HER2 mutation: Final results from the IFCT-1703 R2D2 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9015-9015
Author(s):  
Julien Mazieres ◽  
Claire Lafitte ◽  
Charles Ricordel ◽  
Laurent Greillier ◽  
Jean-Louis Pujol ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Overall Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Loading Dose ◽  
Overall Response ◽  
Grade 3 ◽  
Exon 20

9015 Background: Human epidermal growth factor receptor 2 ( HER2) exon 20 insertions and mutations are oncogenic drivers found in 1-2% of NSCLC. However, there are no approved therapies for these patients. Many studies suggest that the use of HER2 inhibitors developed for breast cancer patients might be of interest in this setting. The aim of this trial was to prospectively evaluate the interest of a combination of two antibodies against HER2 (trastuzumab and pertuzumab) with docetaxel. Methods: IFCT-1703 R2D2 trial is a multicenter, non-randomized phase 2 study with a two-stage design, a power of 90% and an alpha risk at 5% (one-sided). HER2 mutational status was assessed locally in certified molecular genetic centers. Main other inclusion criteria were advanced NSCLC, progression after ≥ 1 platinum-based chemotherapy, asymptomatic brain metastases, left ventricular ejection fraction (LVEF) ≥ 50%, and PS 0-2. Patients were treated every 3 weeks with pertuzumab at a loading dose of 840 mg, and 420 mg thereafter; plus trastuzumab at a loading dose of 8 mg/kg and 6 mg/kg thereafter; and docetaxel at 75 mg/m². Treatment was given until toxicity or disease progression. The primary outcome was overall response rate (ORR). Other endpoints included duration of response, progression-free survival and safety. NCT number: NCT03845270. Results: From May 2019 to October 2020, 45 patients were enrolled in 17 centers and received study treatment. Median age was 64.5 years (range 31–84), 72% females, 35% smokers, 100% non-squamous histology and 15% with ECOG PS 2. 31.1% patients had brain metastases. PD-L1 was expressed ≥ 1% and ≥ 50% in 36% and 7% of the patients, respectively. No other oncogene driver was found associated with HER2 exon 20 mutation. With a median follow-up of 12 months, 44 (98%) patients were evaluable for the primary endpoint. Overall response rate was 29% (n = 13), stable disease 56% (n = 26). Median PFS was 6.8 months (95% CI[4.0-8.5]). Median duration of treatment in patients with confirmed response (n = 13) was 10 months (95% CI[2.7-14.9]). At the time of data cut-off, 15 patients (33%) were still under treatment. Grade 3/4 treatment-related adverse events (AEs) were observed in 64% of patients. No patient experienced treatment discontinuation because of toxicity. One sudden death was possibly related to treatment. Most frequent grade ≥ 3 AEs were neutropenia (33%), diarrhea (13%) and anaemia (9%). Grade 1/2 dyspnea was observed in 3 (6.7%) patients. No ILD were reported. Variation LVEF was -1.72% on average (min: -18 %; max: 10 %). Conclusions: The triplet trastuzumab, pertuzumab and docetaxel is feasible and active in HER2 pretreated advanced NSCLC. These results confirm the activity of HER2 antibodies-based strategy which should be considered in these patients. Clinical trial information: NCT03845270.

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