Phase II trial of sequential temozolomide (TMZ) and high-dose bolus (HDB) IL-2 in patients with metastatic melanoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8037-8037
Author(s):  
S. S. Agarwala ◽  
A. A. Tarhini ◽  
J. M. Kirkwood ◽  
C. Cai ◽  
L. Stover ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Single Agent ◽  
Stage Iv ◽  
Median Number ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Female Age ◽  
Grade 3

8037 Background: Previous biochemotherapy (BCT) regimens for metastatic melanoma have utilized lower doses of IL-2 and multiple chemotherapeutic agents, adding to toxicity, but not to efficacy. Methods: We designed a 2-stage Simon phase II study testing a unique BCT approach of single agent chemotherapy with TMZ given in an extended schedule (75 mg/m² per day for 3 weeks PO) followed by HDB IL-2 (600,000 U/Kg/dose, maximum 14 doses administered over 5 days). Cycles were repeated every 28 days with a two-week interval between alternate cycles. The first stage accrued 20 patients with promising activity and safety permitting enrollment of additional patients. Results: Thirty-one patients (20 male, 11 female), age 27–74 (median 47) have been enrolled to date. All had AJCC stage IV melanoma (7 M1a, 5 M1b, 19 M1c) and had not previously received therapy for metastatic disease. Twelve had received prior adjuvant interferon. A total of 88 cycles of therapy have been administered (median of 2 cycles per patient; 5 patients continue on therapy). The median number of doses was 9 (range 7–12) during cycle 1, and 6 (range 4–11) during cycle 2. Three patients did not receive any IL-2 due to disease progression, and 6 patients received only one cycle of IL-2. Twenty two patients who received at least 2 cycles are evaluable for response. All 31 patients are evaluable for toxicity. Grade 3 toxicities included hepatic (8), hematologic (4 leukopenia, 2 thrombocytopenia), diarrhea (1). No grade 3–4 cardiovascular or renal toxicities were noted. Overall response rate is 22.7% (2 complete lasting 10.8 and 17+ months, 3 partial lasting 3.7 and 16+ months, 1+ month). Responses were seen in both M1a and M1c disease. Fourteen patients had stable disease after 2 cycles and 10 of these have progressed. As of 12/31/2005, the 4 month PFS rate is 74% [40%, 88%], median TTP is 24 weeks [11, 32] and median OS is 71 weeks (31.4, inf). Conclusions: HDB IL-2 can be safely administered in combination with single agent temozolomide in an extended schedule and appears to have promising efficacy and lower toxicity than previously used BCT regimens. Further follow-up will determine if durability of response exceeds that of single agent HDB IL-2. [Table: see text]

Low-dose gemcitabine and radiation alternated to cisplatin/5fu in stage IV squamous cell carcinoma of the head and neck (HN- SCC): A phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6062-6062
Author(s):  
M. Benasso ◽  
V. Vigo ◽  
A. Bacigalupo ◽  
A. Ponzanelli ◽  
M. Marcenaro
Keyword(s):  
Phase Ii ◽  
Low Dose ◽  
Stage Iv ◽  
Standard Of Care ◽  
High Dose ◽  
Local Toxicity ◽  
Grade 3 ◽  
Present Trial ◽  
Severe Mucositis

6062 Background: At the National Institute for Cancer Research of Genoa, Italy, we conducted two consecutive phase II single-institution trials testing the addition of gemcitabine into an alternating chemo-radiation (CT/RT) regimen that is considered standard of care in our Institute for patients (pts) with loco-regional advanced HN-SCC (NEJM, 327:1115,1992). In the former trial (ALT-G trial; 47 pts) high dose gemcitabine was administered with cisplatin and RT (Annals of Oncology, 15:646,2004). Methods: In the present trial (ALT-g trial) 3 courses of cisplatin, 20 mg/m2/day and 5-fluorouracil, 200 mg/m2/day, days 1–5 (weeks 1, 4, 7) alternated to 3 courses of standard RT (weeks 2–3, 5–6, 8–9) up to 60 Gy and gemcitabine, 40 mg/m2 on monday of each week of RT, were administered to 47 pts with stage IV (42 pts) or relapsed after surgery (5 pts), unresectable SCC of the oral cavity (11 pts), oropharynx (11 pts) hypopharynx-larynx (24 pts). None had previously received CT or RT. Results: Seven pts (15%) did not complete the planned treatment. Four of them died due to pulmonary embolism (2 pts), fulminant pneumonia (1 pt) or uncertain causes (1 pt). Main grade 3–4 other than local toxicities were: neutropenia (11%), neutropenia with fever (6%), thrombocytopenia (30%), anemia (17% grade 3). 27 pts reached a CR (57%). 7 PRs were rendered disease-free by surgery mainly on the neck (final CR rate: 72%). At a median follow-up of 37 months, 3-yr results and acute local toxicity are compared with those from ALT-G trial and from our data-base of pts treated with alternating cisplatin/5-FU and RT without gemcitabine (ALT): Conclusions: In conclusion, the addition of low-dose gemcitabine into a consolidated cisplatin/5FU and RT alternating program may improve the outcomes with an acceptable increase in acute severe mucositis. No significant financial relationships to disclose. [Table: see text]

Phase II study of the IDH2-inhibitor enasidenib in patients with high-risk IDH2-mutated myelodysplastic syndromes (MDS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7010-7010
Author(s):  
Sangeetha Venugopal ◽  
Courtney Denton Dinardo ◽  
Koichi Takahashi ◽  
Marina Konopleva ◽  
Sanam Loghavi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Median Number ◽  
International Prognostic Scoring System ◽  
Open Label ◽  
Isocitrate Dehydrogenase 2 ◽  
Treatment Naïve ◽  
Grade 3

7010 Background: Isocitrate dehydrogenase 2 ( IDH2) mutations occur in 5% of patients (pts) with MDS. Enasidenib (ENA) is a selective oral inhibitor of the mutant IDH2 enzyme with single-agent activity in relapsed/refractory acute myeloid leukemia (AML). We report the results of the open label phase II study designed to evaluate the efficacy and tolerability of ENA, as monotherapy or in combination with azacitidine (AZA) in pts with higher-risk IDH2-mutated MDS (NCT03383575). Methods: Pts with higher-risk [Revised International Prognostic Scoring System risk > 3 or high molecular risk (HMR)] MDS/CMML or LB AML naïve to hypomethylating agents (HMA) received ENA100 mg orally daily for 28 d of each 28-d cycle + AZA 75 mg/m2 IV or SC on d 1-7 of each cycle (ENA+AZA), and pts with refractory or progressive MDS to prior HMA therapy received ENA alone (ENA), in 28-d cycles until unacceptable toxicity, relapse, transformation to AML, or progression. The primary endpoint was overall response rate (ORR) [complete remission (CR), marrow CR (mCR), partial remission (PR) and hematologic improvement (HI)]. Other endpoints include safety, and survival outcomes. Results: 48 pts received ENA+AZA (n = 26) or ENA (n = 22). The median age was 73 yrs (range, 46-83). Most pts (72%) had HMR: ASXL1 (39%), and RUNX1 (17%). Median number Tx cycles was 4 (2–32) in the ENA+AZA, and 7 (1–23) in the ENA arm. Common Tx-related grade 3–4 AEs in the ENA+AZA arm were neutropenia (64%), thrombocytopenia (28%), and anemia (8%); these occurred in 10%, 0%, and 5%, in the ENA arm. Grade 3–4 infections occurred in 32% (ENA+AZA) and 14% (ENA). IDH differentiation syndrome occurred in 3 pts (12%) in the ENA+AZA and 5 pts (24%) in the ENA arm. Two deaths occurred during the initial 60 d, both unrelated to study and due to COVID. In response-evaluable pts (n=46), ORR was 84% (n = 21/25; 24% CR + 8% PR+44% mCR+ 8% HI] in the treatment naïve ENA+AZA and 43% (n = 9/21; 24% CR+5%PR+5% mCR+10% HI) in the HMA failure ENA arm (Table). Most common reason for Tx discontinuation was disease progression (ENA+AZA 20%, ENA 33%).5 pts (20%) received HCT in the ENA+AZA and 1 (5%) in the ENA arm. 7 pts in the ENA+AZA and 5 in the ENA arm were ongoing at data cutoff (Dec 31, 2020). After a median follow up of 12.6 mo, median OS was 32.2 mo in the ENA+AZA and 21.3 mo in the ENA arm. Conclusions: ENA is well tolerated and shows promising efficacy in IDH2-mutated higher risk MDS. Follow up and accrual is ongoing to better define duration and biomarkers of response. Clinical trial information: NCT03383575. [Table: see text]

Phase II study of NGR-hTNF, a selective vascular targeting agent (VTA), administered as single agent in patients (pts) with colorectal cancer (CRC) refractory to standard regimens

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4088-4088
Author(s):  
L. Rimassa ◽  
A. F. Sobrero ◽  
A. Santoro ◽  
V. Andretta ◽  
V. Gregorc ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Biological Agents ◽  
Stage Design ◽  
High Doses ◽  
Grade 3 ◽  
Post Hoc

4088 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to an aminopeptidase N/CD13 overexpressed by tumor blood vessels. In preclinical models, NGR-hTNF showed antitumor activity both at low and at high doses. Methods: Pts with CRC resistant/refractory to standard treatments, including biological agents, were treated with low-dose NGR-hTNF given intravenously at 0.8 μg/m2 as 1-hour infusion every 3 weeks (q3w). This phase II trial had a 2-stage design with 16 and 27 pts to be enrolled after first and second stage, respectively. Progression-free survival (PFS) was the primary end-point with reassessment performed q6w. Results: From January to May 2007, 33 pts with radiologically- documented progressive disease after last therapy were evaluated over 111 cycles (range, 1–10). Pts characteristics were: median age: 65 years (range, 53 to 79); M/F 16/17; PS 0/1 26/7. Median number of prior regimens was 3 (range, 2 to 5). Eight pts (25%) were pre-treated with ≥4 lines and 22 (67%) with biological agents. Neither grade 3–4 treatment-related adverse events nor toxicity-related deaths were observed. Main grade 1–2 toxicities per patient were infusion-related chills (47%) and transient blood pressure increase (9%). One partial response (3%) lasting 5 months and 12 stable diseases (36%) were reported. Median PFS was 2.5 months (95% CI, 2.2–2.8). In a post-hoc analysis, no differences in PFS were detected according to baseline characteristics. With a median follow-up time of 18.4 months (95% CI, 18.3–18.5), 11 pts (33%) were still alive. Median overall survival (OS) was 13.1 months and the 2-year OS rate was 22%. In the subset of stable or responder pts, the median PFS and OS were 3.8 months and 15.4 months, respectively. The 6-month PFS rate in the prior-biological and biological-naïve cohorts was 5% and 20%, respectively, whereas 1-year OS rate was 41% and 72%, respectively. Conclusions: Based on the favorable toxicity profile and disease control in heavily pre-treated CRC patients, NGR-hTNF will be further developed in combination with standard chemotherapy. [Table: see text]

Nivolumab/pembrolizumab in Child-Pugh grade B/C patients with advanced HCC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16184-e16184
Author(s):  
Jeffrey Sum Lung Wong ◽  
Gin Wai Kwok ◽  
Vikki Tang ◽  
Bryan Li ◽  
Roland Ching-Yu Leung ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Median Number ◽  
Refractory Ascites ◽  
Time To Progression ◽  
Advanced Hcc ◽  
Grade 3 ◽  
Experienced Grade ◽  
Systemic Therapies

e16184 Background: Hepatic derangement commonly accompanies advanced HCC (aHCC) and limits the use of systemic therapies. We aimed to evaluate the use of single agent anti-PD-1 nivolumab or pembrolizumab in Child-Pugh (CP) grade B or C patients with aHCC. Methods: Consecutive aHCC patients with CP grade B (CPB) or C (CPC) liver function who received single agent nivolumab or pembrolizumab were analysed. Objective response rate (ORR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Results: Between May 2015 and June 2020, 61 patients were included. The median age was 60 (range 28-82). 81% and 4.8% had hepatitis-B and hepatitis-C related HCCs respectively. 72.1% (n = 44) were of CPB and 27.9% (n = 17) were of CPC. Amongst CPB patients, 19 (31.1% of all patients) had CP score 7 (CP7) and 25 (41.0% of all patients) had CP score 8 or 9. The median follow-up was 2.3 months. The ORR of CPB and CPC patients were 6.8% and 0% respectively (p = 0.553). The TTP of CPB and CPC patients were 2.1 months (95% C.I. 1.4-2.8) and 1.4 months (95% C.I. 0.6-2.1) respectively (p = 0.204). CPB patients had significantly better OS than CPC patients (3.1 months (95% C.I. 1.4-4.7), vs. 1.7 months (95% C.I. 1.0-2.4), p = 0.041). Compared to CP score ≥8 (CP≥8) patients, CP7 patients had significantly better OS (median OS CP7 6.7 months (95% C.I. 4.0-9.3), vs. CP≥8 1.8 months (1.2-2.4), p = 0.002). Patients with diuretic-refractory ascites had significantly worse OS compared to those without (1.7 months (95% C.I. 1.0-2.5) vs. 3.7 months (95% C.I. 0.1-7.3), p = 0.004). Portal vein (PV) thrombosis was also significantly associated with inferior survival, with median OS of patients with any PV thrombosis being 1.8 months (95% C.I. 1.0-2.5), compared to 5.3 months (95% C.I. 2.4-8.1) of those without (p = 0.004). The median number of doses given was 3 (range 1-34). Median treatment duration was 5.0 weeks (range 0-77). Overall, 25.4% of patients experienced TRAEs and 4.8% experienced grade ≥3 TRAEs. The most common TRAEs were skin-related (13.1%) and constitutional symptoms (6.6%). Conclusions: Nivolumab/pembrolizumab had acceptable safety in CPB/C patients with aHCC. CP7, absence of diuretic-refractory ascites and lack of PV thrombosis were associated with better survival.

A Phase II Study of Temsirolimus (CCI-779) in Patients with Advanced Leukemias.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4523-4523 ◽  
Author(s):  
Karen W.L. Yee ◽  
Guillermo Garcia-Manero ◽  
Deborah Thomas ◽  
Farhad Ravandi-Kashani ◽  
Srdan Verstovsek ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Blast Crisis ◽  
Single Agent ◽  
Mammalian Target Of Rapamycin ◽  
Median Number ◽  
Prior Therapy ◽  
Flat Dose ◽  
Grade 3

Abstract Temsirolimus (CCI-779, Wyeth Pharmaceuticals) has been shown to inhibit proliferation of a variety of tumors and induce G1 cell cycle arrest by preventing activation of the serine/threonine kinase, mTOR (mammalian target of rapamycin), a downstream effector of the PI3K/Akt pathway. Several lines of evidence implicate the PI3K/Akt/mTOR pathway in hematological malignancies. Interim results of a phase II study evaluating the efficacy and toxicity of single-agent temsirolimus in patients with advanced malignancies are presented. Temsirolimus was administered weekly, at a flat dose of 25 mg, as a 30-minute intravenous infusion. Treatment was continued until evidence of disease progression or unacceptable toxicity. To date, 8 patients have been enrolled and 7 are evaluable for efficacy and toxicity (one patient did not receive temsirolimus). Of these 7 patients, 5 had AML, 1 CML-myeloid blast crisis, and 1 ALL. Median age was 68 years (range, 21 to 87 years) and 5 were male. All patients had received prior therapy, median 2 regimens (range, 1 to 3 regimens). The median number of temsirolimus doses administered was 3 (range, 1 to 10) with a median time on study of 18 days (range, 3 to 89+ days). The most common temsirolimus-related adverse events were grade ≤ 2 and consisted of anorexia, nausea and/or vomiting and diarrhea, mucositis, dermatitis, hypertriglyceridemia, hyperglycemia, hypomagnesemia, hypocalcemia, hypokalemia, hypophosphatemia, and fatigue/asthenia. No patient developed nonspecific pneumonitis. Grade 3 toxicities included fatigue/asthenia (2), hyperglycemia (1), painful mucositis with dehydration and electrolyte abnormalities (1), diarrhea with hypokalemia (1), and hypophosphatemia (1). No patient experienced grade 4 toxicities or death from temsirolimus. No patient required dose reductions, but 2 did have dose delays due to grade 3 mucositis (1) and out-of-state hospitalization for pneumonia and atrial fibrillation (1). No patient achieved a complete remission. One patient with heavily pre-treated Philadelphia-negative precursor B-cell ALL had a transient 79% to 91% reduction in peripheral blood blasts 4 days after the first dose of temsirolimus that was maintained for 12 days prior to disease progression with involvement of the synovial fluid in bilateral knees. At the time of analysis, 6 of the 7 patients have discontinued treatment due to disease progression (4), patient refusal (1), or physician decision (1). Preliminary findings indicate that temsirolimus is relatively well-tolerated at a dose of 25 mg per week and may have biologic activity in ALL. Accrual onto the study is currently ongoing.

Retrospective Analysis of Fractionated High-Dose Melphalan (F-MEL) and Bortezomib-Thalidomide-Dexamethasone (VTD) with Autotransplant (AT) Support for Advanced and Refractory Multiple Myeloma (AR-MM).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3102-3102 ◽  
Author(s):  
Mauricio Pineda-Roman ◽  
Michelle H. Fox ◽  
Klaus A. Hollmig ◽  
Elias J. Anaissie ◽  
Frits van Rhee ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Single Agent ◽  
Patient Characteristics ◽  
Median Number ◽  
Outpatient Setting ◽  
High Dose ◽  
Life Threatening ◽  
Grade 3 ◽  
High Dose Melphalan ◽  
Asco 2006

Abstract Background: MEL is an effective and safe AT regimen for MM, usually administered as a single dose at 200mg/m2; mucositis is dose-limiting. There is recent pre-clinical and clinical evidence of synergistic interaction of MEL with both immuno-modulatory agents (thalidomide, MPT [Palumbo, Lancet, 2006], lenalidomide, RMP [Palumbo, ASCO, 2006]) and with the first-in-class proteasome inhibitor, bortezomib (VelcadeR) (VMP, Mateos, ASCO, 2006). We previously reported on the marked activity of VTD in AR-MM, even in a setting of resistance to single agent thalidomide and bortezomib (Blood, January, 2004). In a clinical setting of AR-MM, we administered IV MEL after bortezomib (V) on days 1, 4, 7 +/− d 10, along with daily thalidomide (T) and dexamethasone (D), in order to achieve maximum pharmacological synergy of all 4 drugs. Patients and Methods: A retrospective analysis was performed of 22 patients with AR-MM, who were treated with the F-MEL-VTD regimen with the following MEL fractions: 3-F at 50–80mg/m2 for total doses of 150–240 mg/m2, 18 patients; 4-F at 50–60mg/m2 for total doses of 200–240 mg/m2, 4 patients; 5-F at 15–50 mg/m2 for total doses of 150–250 mg/m2, 2 patients. V was given at doses of 1.0–1.3 mg/m2 immediately preceding each MEL fraction; T was dosed at 100–200 mg/d from day 1 until the last day of MEL; D was given at 20–40 mg on the day of and after V and MEL. Two patients received 2 cycles of F-MEL-VTD, so that 24 courses could be evaluated. Results: Patient characteristics included a median age of 61yr (range, 46–75yr), median creatinine of 0.85mg/dL (range, 0.6–1.9mg/dL); abnormal cytogenetics (CA) were present in 15/22 (68%) - typifying the high-risk nature of their disease; the median number of prior regimens was 6 (range, 1–14); prior AT: 0 in 3 patients, 1 in 11, 2 in 8 and 3 in 1 patients. F-MEL-VTD was initiated in the outpatient setting in 15, only 3 of whom required subsequent hospital admission. Toxicities included grade 3–4 diarrhea mainly due to C. difficile in 8 (33%) and oral mucositis > grade 2 in only 1; grade 3 fever in 3 (12%) with Aspergillus pneumonia in 2 patients; no transplant-related mortality. Hematopoietic recovery was excellent with median times to ANC>500/microL of 10 days (range, 8–19d) and platelets > 50.000/microL of 17 days (range, 10–24d); 2 patients receiving 1.88 and 1.95 x 106 CD34+ cells/kg failed to recover platelet counts to >50.000/microL. Response rates were measured at 6 weeks, using Blade criteria: CR, 11 (46%) with an additional 3 achieving near-CR (>=n-CR, 59%); PR, 4 (17%); the remainder 24% had transient or no response. Conclusion: F-MEL-VTD was remarkably well tolerated, permitting total MEL dose escalation to > 200mg/m2 in 13 of 22 patients, without incurring grade >2 stomatitis in the majority of patients. Due to the protracted administration involved in this regimen, the median duration of neutropenia was 10 d (range, 8 to 19d) with life-threatening infections observed in only 2 patients. These encouraging data form the basis for a randomized trial of VTD followed by standard 1-F MEL versus 3-F MEL with VTD preceding each MEL dose.

Durable Responses with Bortezomib in Patients with Relapsed or Refractory Mantle Cell Lymphoma (MCL): Updated Time-to-Event Analyses of the Multicenter PINNACLE Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 125-125 ◽  
Author(s):  
Andre Goy ◽  
Steven Bernstein ◽  
Brad Kahl ◽  
Benjamin Djulbegovic ◽  
Michael Robertson ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Median Time ◽  
International Workshop ◽  
Single Agent ◽  
Stage Iv ◽  
Time To Event ◽  
Prior Therapy ◽  
Duration Of Response ◽  
Grade 3

Abstract Background: We previously reported substantial activity with single-agent bortezomib (VELCADE®; Vc) in patients (pts) with relapsed or refractory MCL in the PINNACLE study (JCO2006;24:4867–74), which resulted in approval of Vc for MCL pts following ≥1 prior therapy. All pts have now completed treatment. Here we report updated time-to-event data in all pts, and by response category, with extended follow-up. Methods: 155 pts (median age 65 yrs; 55%/41%/4% with 1/2/≥3 prior therapies; 77% Stage IV MCL; 55% positive bone marrow) received Vc 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles; of these, 141 were response-evaluable. Response and progression were determined by modified International Workshop Response Criteria using independent radiology review. Results: After a median follow-up of 26.4 mo, 55 pts (35%) remained in follow-up; 93 (60%) had died, 2 (1%) had withdrawn consent, and 5 (3%) were lost to follow-up. Pts received a median of 4 treatment cycles (range 1–21; 8 in responding pts). Median time to first response was 1.3 months. Median duration of response (DOR) was 9.2 mo in all responders and has not been reached in pts achieving CR/CRu. Median time to progression (TTP), time to next therapy (TTNT; first Vc dose to start of next therapy), and overall survival (OS) are shown in the table for all pts and by response. Survival rate at 12-mo was 69% overall and 91% in responding pts. In pts refractory to their last therapy (no response or response with TTP <6 mo; n=58), median DOR was 5.9 mo, median TTP was 3.9 mo, median TTNT was 4.6 mo, and median survival was 17.3 mo. Safety profile was similar to previously reported; most common grade ≥3 AEs were peripheral neuropathy (13%), fatigue (12%), and thrombocytopenia (11%). The most common AE resulting in Vc discontinuation was peripheral neuropathy (10%). Twelve (8%) pts died on-study, including 5 (3%) considered related to Vc. Conclusions: Vc provides durable responses plus prolonged time off-therapy and survival in responding pts, suggesting substantial clinical benefit in relapsed/refractory MCL. Median TTP, TTNT, and OS (months) in all pts and by response All pts (N=155) Responders (N=45) CR/CRu (N=11) PR (N=34) SD (N=52) PD (N=34) NE, not estimable TTP 6.7 12.4 NE 9.1 6.9 1.2 TTNT 7.4 14.3 23.9 13.3 7.0 2.3 OS 23.5 35.4 36.0 35.1 27.8 13.7

High-Dose Cytoxan, Etoposide, and Cisplatin Followed by Autologous Hematopoietic Cell Transplantation for the Treatment of Hodgkin Lymphoma: A 20-Year Single-Institutional Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1913-1913
Author(s):  
Thomas R. Klumpp ◽  
Moshe C. Chasky ◽  
Robert V. Emmons ◽  
Mary E. Martin ◽  
James L. Gajewski ◽  
...  
Keyword(s):  
Complete Remission ◽  
Total Dose ◽  
Hodgkin Lymphoma ◽  
Pulmonary Toxicity ◽  
Median Number ◽  
High Dose ◽  
Post Transplant ◽  
Grade 3 ◽  
Active Disease

Abstract Since 1988 we have treated 66 patients with relapsed, refractory, or high-risk Hodgkin lymphoma (HD) with high-dose CEP consisting of cyclophosphamide 1,500 mg/m2/day × 4 (total dose, 6,000 mg/m2), etoposide 400 mg/m2 twice daily × 6 doses (total dose, 2,400 mg/m2), and cisplatin 50 mg/m2/day × 3 by continuous i.v. infusion (total dose 150 mg/m2) followed by infusion of autologous peripheral blood stem cells (n=49), bone marrow (n=16), or both (n=1). The patient population included 41 males and 25 females. The median age at transplant was 33 years (range, 17–64 years). Twenty-three patients (35%) had never achieved complete remission prior to transplant, 36 (55%) had previously achieved a complete remission but subsequently relapsed, and 3 (5%) were in first complete remission. Information regarding the disease status at transplant was unavailable for 4 patients (6%). Twenty-seven patients (41%) remain alive and free of any post-transplant relapse or progression as of the most recent follow-up, and an additional 10 patients (15%) manifested active disease post-transplant but are currently in remission following additional post-transplant therapy, yielding a total of 37 patients (56%) currently in CR. In addition, 5 patients (8%) remain alive with active disease, 23 patients (35%) died of progressive disease, and only 2 patients (3%) died of treatment-related causes including diffuse alveolar hemorrhage (1 patient) and hepatic veno-occlussive disease (1 patient). With a median follow-up of 4.4 years among surviving patients, the Kaplan-Meier 5-year estimates for event-free survival and overall survival are 34% and 60%, respectively, and five-year survival was superior among patients who had achieved at least one CR prior to transplant versus patients who had never been in CR prior to transplant (71% versus 43%, p = 0.03). Detailed adverse events data is available regarding all patients transplanted since September 1996: Of these, only 3 (7%) suffered grade 3 or greater pulmonary toxicity, 12 (29%) exhibited grade 3 or higher mucositis, and 10 (24%) had grade 3 or higher nausea or vomiting. The median number of days from transplant to neutrophil recovery (500 cells/uL) was 10 days, whereas the median number of days to platelet recovery (20,000 cells/uL) was 12 days. We conclude that high- dose CEP followed by autologous transplant is an active and well-tolerated treatment program in patients with relapsed or refractory HD. The low incidence of pulmonary toxicity is noteworthy given that a high percentage of patients had been exposed to bleomycin and/or thoracic XRT prior to transplant, and appears to be superior to that reported with conventional CBV-conditioned transplants in patients with HD.

A Phase II Study of Decitabine In Advanced Chronic Myelomonocytic Leukemia (CMML)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1873-1873
Author(s):  
Thorsten Braun ◽  
Nathalie Droin ◽  
Benoit de Renzis ◽  
Francois Dreyfus ◽  
Kamel Laribi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Conflicts Of Interest ◽  
Cytogenetic Response ◽  
Median Number ◽  
Costal Margin ◽  
Monocyte Count ◽  
Blood Monocytes ◽  
Grade 3 ◽  
Wbc Count

Abstract Abstract 1873 Background: CMML, now classified among MDS/MPN, is prognostically heterogeneous. We (JCO 1988 6:1417, Blood 1996 88:2480) and others found prognosis in CMML to depend on both “MDS factors” (% marrow blasts, cytopenias, karyotype) and “MPN” factors, ie splenomegaly (SMG), WBC count, extramedullary disease (EMD). Treatment of advanced CMML is difficult. The hypomethylating agents Azacitidine and Decitabine (DAC) have shown efficacy in CMML, but in prognostically heterogeneous cohorts. We conducted a phase II trial of DAC in a well defined cohort of advanced CMML. Methods: To be included, CMML (according to WHO) should have: if WBC<13G/l an IPSS≥1.5; if WBC≥13G/l, two of the following criteria: marrow blasts≥5%, Hb<10g/dl, plts<100G/l, abnormal cytogenetics, SMG >5cm below costal margin, (SMG>5cm), EMD, based on our previous prognostic factors. Pts received DAC 20mg/m2/d IV for 5 days every 28 days for at least 3 cycles. Response criteria were based on IWG 2006 for pts with WBC <13G/L and for pts with WBC > 13 G/L also included evolution of WBC, SMG and EMD (Blood 1996 88:2480). Results: Between Nov 2008 and June 2009, 41 pts were included in 16 centers, of whom 39 completed at least one cycle and were considered evaluable for response (the 2 other pts died from septic shock before and during the first cycle respectively). Median number of cycles was 9 (range 1–17). Median age was 71 years (range 54–88), M/F:30/9. Seventeen pts had CMML 1 and 22 had CMML 2 (including pts with up to 29% marrow blasts). Median WBC count was 29.5G/l (range 4.1–147.3), median blood monocytes 3G/l (range 1.05–95.7), and median BM blasts 10% (1-29). Nine pts had WBC<13G/l and 30 WBC≥13G/l. Abnormal karyotype was found in 18 (46.2%) pts, including +8 and -7 in 7 and 1 case, respectively. 15 pts (38.6%) had SMG>5cm and 8 (20.5%) EMD involving skin (n=5) and lymph nodes (n=3). Overall Response Rate (ORR,) was 38.6% with 4 (10.3%) CR, 8 (20.5%) marrow CR and 3 (7.7%) Stable Disease (SD) with HI. 1 CR pt received allo SCT. 18 (46%) pts had SD without HI and 6 (15.4%) pts progressed to AML. 8 (36.4%) of the 22 RBC transfused pts became RBC transfusion independent. 3/10 (30%) pts with plt<50G/l reached plt>100G/l. Four pts had cytogenetic response (3 CR and 1 PR) exclusively among pts with +8. Median peripheral monocyte count decreased from 4.8G/l to 0.3G/l after 3 cycles of DAC among responders. SMG disappeared in 6/15 (40%) pts and EMD in 6/8 (75%) pts. 16 pts were receiving Hydroxyurea (HY) at inclusion which could be stopped in 12 of them. With a median follow up of 10 months (1-18), 7 pts had died from progression (n=3), sepsis (n=3) and unrelated cause (n=1). Overall Survival (OS) estimate was 60% at 2 years (median not reached). By comparison, in our previous trial of HY in CMML where inclusion criteria were the same, 2 year survival was 43% (median OS 20 months; Blood 1996 88:2480), for a median follow up of 11 months (range1-43). The only factor associated with response to DAC was WHO subtype, CMML 2 pts showing significantly better ORR (30.8% vs 7.7% in CMML 1; p=0.041).There was no difference in survival between CMML 1 and 2 pts. Treatment with DAC was generally well tolerated with, except for usual grade 3/4 cytopenias, and grade 3 fatigue (n=1). Conclusion: DAC is active in advanced CMML and safe in these elderly pts. A possibly better survival than with HY will have to be confirmed in randomized trials. Correlative genetic studies identifying markers potentially predicting response and survival for DAC are currently underway in our lab. Disclosures: No relevant conflicts of interest to declare.

Combination Biologic Therapy as Initial Treatment for Follicular Lymphoma: Initial Results From CALGB 50701 - a Phase II Trial of Extended Induction Epratuzumab (anti-CD22) and Rituximab (anti-CD20)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 427-427 ◽  
Author(s):  
Barbara Grant ◽  
John P. Leonard ◽  
Jeffrey L Johnson ◽  
Lale Kostakoglu ◽  
Eric Hsi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Follicular Lymphoma ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Good Tolerability ◽  
Grade 3 ◽  
Anti Cd20

Abstract Abstract 427 Rituximab is effective as single agent therapy in the treatment of follicular lymphoma (FL), and when combined with chemotherapy has extended remissions and survival. Epratuzumab (Immunomedics), a humanized anti-CD22 monoclonal antibody, also has single agent activity in FL, and in combination with rituximab led to durable complete responses in the treatment of patients (pts) with relapsed and refractory indolent NHL. To evaluate the hypothesis that combining a second biological agent with rituximab might improve efficacy with good tolerability, the CALGB treated 60 previously untreated pts with epratuzumab and rituximab in a multicenter phase II trial and we report here the preliminary response and toxicity findings. Rituximab was administered at 375 mg/m2 iv weekly for four weeks, then every 8 weeks for four additional doses for a total of 8 doses over 9 months. Epratuzumab, was given at 360 mg/m2 two days before the first rituximab dose to assess toxicity. From week 2 on, epratuzumab was given before the rituximab on the same day for a total of 8 doses over 9 months. Fifty-seven evaluable pts were enrolled between May 2008 and September 2009. FLIPI scores at study entry were 13 (22%) low; 28 (47.5%) intermediate; and 18 (30.5%) high. Fifty-three pts completed all therapy through month 9. One pt was taken off therapy due to progression after month 5. One pt died during induction from line sepsis. Two pts were taken off study due to adverse events, 1 during induction (grade 4 thrombosis and MI), 1 following month 5 (dyspnea, hypoxia and pulmonary NOS). All other toxicities were grade 3 or lower, including fatigue (grade 3 3%, grade 2 17%), nodal pain (grade 3 5%, grade 2 8%), and cytokine release and pruritis (grade 2, 5% each). To date, there have been 19 CRs (33.3%), 29 PRs (50.9%)(ORR 84.2%); 9 (15.8%) had stable disease. All 19 CR patients completed all treatment. The mean time to CR was 9 months. Two patients progressed after a period of stable disease, and 25 of the 29 patients who achieved PR remain in response. All 19 CRs also remain in remission at this point with a median follow-up of 0.82 years (range 0.52 to 2.0). FLIPI score was not predictive of response. The CR rate in low risk pts was 31%, 44% in intermediate risk and 18% in high risk pts. There was a trend toward higher CR rate among patients with FcgR2A His (n=10, CR 60%) and to a lower CR rate among those with FcgR2A Arg (n=14, CR 14.3%). Correlations with PET scan at week 3, with tissue biomarkers and to statin use are being analyzed. Rituximab and epratuzumab is an effective and very well tolerated regimen with an ORR of 84% in previously untreated patients with follicular lymphoma. Disclosures: Off Label Use: Use of Epratuzumab, a humanized antiCD22 monoclonal antibody in treatment of follicular lymphoma. Leonard:BiogenIDEC: Consultancy; Genentech: Consultancy; Immunomedics: Consultancy. Jones:Glaxo Smith-Kline: Consultancy; Abbott: Research Funding. Cheson:Genentech: Consultancy.

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