Early Results of a Phase II Trial Testing Low Dose Total Body Irradiation (LTBI) after Chemoimmunotherapy in Elderly High Risk Patients with Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1296-1296
Author(s):  
Akmal Safwat ◽  
Lena Specht ◽  
Flemming Hansen ◽  
Mads Hansen ◽  
Jesper Jurlander ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Early Results ◽  
Trial Testing ◽  
Risk Patients ◽  
Total Body

Abstract Background: The addition of rituximab (R) to bi-weekly CHOP (CHOP-14) in the RICOVER-60 trial resulted in improved time to treatment failure in 828 elderly (61–80 years) DLBCL patients (Blood106:9a, 2005). We investigated the addition of LTBI in a dose of 1,6 Gy given as adjuvant therapy in high-risk elderly patients with DLBCL treated according to the best performing arm of the RICOVER-60 trial (R-CHOP-14 x 6 + 2xR). Methods: A phase II trial including pts >60 yrs with stage II-IV, CD20-positive DLBCL was performed between 2003 and 2007. Pts received 6x R-CHOP-14 and 2 x R alone followed by LTBI given as 2 courses of 4 daily fractions of 0,2 Gy separated by 2 weeks of rest. Results: We report the results of the first 36 patients. The median age was 69 years; 56% had ≥ 1 extranodal lesion; 67% had stage III or IV; 48% had B symptoms and 37% had Bulky (> 7.5 cm) disease; 54% had ECOG score ≥ 1; 75% had elevated LDH and 63% had IPI of >2, while 73% stained positive for BCL2 in pre-therapeutic histological samples. One patient got off study because of the discovery of breast cancer and one patient refused to get LTBI. Twenty one pts achieved a CR or CRu at the end of chemotherapy (58%), 10 (27%) were in PR while only one patient progressed under chemotherapy. All 10 PR pts achieved CR in the first follow up after LTBI. Four pts relapsed within 12 months after achieving CR. All treatment failures occurred in patients with IPI 3&4. Of the administered R-CHOP-14, Rituximab and LTBI cycles, 95%, 100% and 96%, respectively, were given in full dose and on time. CTC Gr 3–4 neutropenia occurred following 50 of 250 R-CHOP-14 cycles (20%). There were 3 toxic deaths (7.8%) due to sepsis occurring during chemotherapy. CTC Gr. 3–4 thrombocytopenia was seen in 8 pts following the last LTBI cycle (22%) and could be prolonged. The 2-Y Overall survival (OS) was found to be 79% (SE ± 8%) while the 2-Y disease free survival (DFS) was 74% (SE ± 10%). Conclusion: In a selected DLBCL group of elderly patients with high-risk prognostic profile, R-CHOP-14 followed by LTBI, although sometimes associated with severe infections and thrombocytopenia, seems to achieve high response rates and provide correspondingly high OS and DFS values.

Final Results of a Phase II Danish Trial Testing Low Dose Total Body Irradiation Following Six Bi-Weekly RCHOP-14 Plus 2 Extra Rituximab in Elderly High risk Patients with Aggressive CD20+ Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1013-1013
Author(s):  
Akmal Safwat ◽  
Lena Specht ◽  
Flemming Hansen ◽  
Mads Hansen ◽  
Jesper Jurlander ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Phase Ii ◽  
Total Body Irradiation ◽  
Low Dose ◽  
B Cell Lymphoma ◽  
Observation Time ◽  
Phase Iii ◽  
Total Body

Abstract Background: To further improve the results achieved by adding Rituximab (R) and shortening chemotherapy interval in elderly patients, an effective but relatively non-toxic treatment modality is needed. We tested therefore the addition of low dose total body irradiation (LTBI) of 1,6 Gy given after chemo-immunotherapy. Methods: A multicenter, phase II trial including patients >60 yrs with stage II-IV, CD20-positive DLBCL was performed between 2003 and 2007. Patients received 6x R-CHOP-14 + 2x R alone followed by LTBI given as 2 courses of 4 daily fractions of 0,2 Gy separated by 2 weeks of rest. Radiotherapy to sites of bulky (>7.5 cm) disease was given according to the local guidelines of the participating centres. Results: Forty two patients were included. Observation time ranged from 3 to 47 months with median follow up of 24 months. The median age was 67 years; 62% had stage III or IV; 48% had B symptoms and 36% had bulky (> 7.5 cm) disease; 50% had ECOG score ≥ 1; 76% had elevated LDH and 57% had IPI of >2. Twenty four patients (57%) achieved a CR or CRu at the end of chemotherapy, while 12 (28.5%) were in PR. One of the 12 PR patients refused LTBI. Of the remaining 11 PR patients who received LTBI, 8 (82%) achieved CR in the first follow up after LTBI while the remaining 3 patients had initially stable disease but progressed shortly after. One patient (2%) progressed under chemotherapy while seven patients (17%) relapsed after achieving CR. Six of these refractory/relapsed cases presented with IPI ≥ 3. The 3-yr event-free and progression-free survival values were 64.8% (SE: 8.7%) and 73.5% (SE: 8.9%), respectively, while the 3-yr overall survival was 85.4% (SE: 5.5%). There were 3 toxic deaths (7.1%) due to sepsis occurring during chemotherapy. Ninteen of 235 cycles of CHOP (8%) were given at reduced dose levels in 3 patients (7%), while 3 cycles (1.3%) were delayed but given at 100% dose level. None of the 305 injections of Rituximab were dose reduced. Only one of 31 patients (3%) got his second LTBI cycle at 75% of the planned dose because of thrombocytopenia. CTC Gr 3–4 neutropenia occurred following 50 of 250 R-CHOP-14 cycles (20%). CTC Gr. 3–4 thrombocytopenia was seen in 8 pts (22%) following LTBI. Conclusions: Despite the high risk profile of the patient cohort enrolled in this trial, the 3-yr outcome values match the results of the best performing recent phase III clinical trials designed for elderly patients with DLBCL. Adding LTBI to 6 cycles of R-CHOP-14 was well tolerated and effective in converting the majority of PRs into CRs. Therefore, it may provide survival benefit and should be tested in a randomised setting.

Imatinib 800 mg: Preliminary Results of a Phase II Trial of the GIMEMA CML Working Party in Intermediate Sokal Risk Patients and Status-of-the-Art of an Ongoing Multinational, Prospective Randomized Trial of Imatinib Standard Dose (400 mg Daily) vs High Dose (800 mg Daily) in High Sokal Risk Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1098-1098
Author(s):  
Gianantonio Rosti ◽  
Giovanni Martinelli ◽  
Fausto Castagnetti ◽  
Nicoletta Testoni ◽  
Giorgina Specchia ◽  
...  
Keyword(s):  
High Risk ◽  
Randomized Trial ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Standard Dose ◽  
Phase Iii ◽  
High Dose ◽  
Molecular Response ◽  
Risk Patients

Abstract The conventional treatment of chronic myeloid leukemia (CML) in early chronic phase (ECP) is imatinib 400 mg daily. The estimated rates of major (MCgR) and complete cytogenetic response (CCgR) at 42 months are 91% and 84%, respectively (IRIS Trial - F Guilhot, ASH 2004), with a survival free from accelerated and blastic phase of 84%. The rates of CCgR are significantly different according to Sokal score, being 91%, 84% and 69% for low, intermediate and high risk categories. Phase I and II trials of imatinib have clearly shown a dose-response effect; more importantly, a single center phase II trial of imatinib 800 mg in ECP showed significantly better results vs standard dose, in terms of CCgR (90% vs 74%) and of complete molecular response (28% vs 7% at 18 months) [H. Kantarjian et al, Blood 103 (8), 2004]. The GIMEMA (Gruppo Italiano Malattie Ematologiche dell’Adulto) CML WP is conducting a phase II trial of imatinib 800 mg in intermediate Sokal risk in ECP (trial CML/021). Overall, 89 pts (mean age 53 yrs) have been enrolled. Fourty-four patients completed 6 months of treatment: the complete hematological response rate is 100%; the MCgR and CCgR are 90% and 81%, respectively. The 6 months CCgR rate of this trial parallels the IRIS trial one in intermediate risk cases (84%), with a much shorter treatment period. The major molecular response rate at 6 months (RTQ-PCR as ratio BCR-ABL/ABL) is 56% (cut-off ≤ 0.12%) or 41% (cut-off ≤0.05%). The compliance to the treatment improved time by time, being 47% the patients receiving ≥ 80% of the scheduled dose between months 1–3 and 60% between months 4 - 6. A second project, exploring imatinib high dose, is reserved to high risk cases: a multinational working group, within the frame of Leukemianet CML WP, is conducting a phase III randomized trial (1:1) of imatinib 400 mg vs 800 mg in high Sokal risk in ECP. By July 31, 2005, 80 patients have been enrolled: GIMEMA CML WP (44 pts), Nordic Countries - Sweden, Denmark, Norway and Finland (25 pts), Turkey (10 pts) and Israel (1 pt).

Prolonged Survival with Low Incidence of CNS Relapse and Late Toxicities in a Retrospective Series of 278 Young Patients with High-Risk (aa-IPI 2–3) Diffuse Large B-Cell Lymphoma Treated with Intensified Chemotherapy with or without Rituximab At Diagnosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1606-1606
Author(s):  
Annalisa Chiappella ◽  
Alessia Castellino ◽  
Maria Giuseppina Cabras ◽  
Anna Marina Liberati ◽  
Andrea Evangelista ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Secondary Malignancies ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Dose Dense

Abstract Abstract 1606 Introduction. Diffuse Large B-cell Lymphoma (DLBCL) patients at high-risk (age-adjusted International Prognostic Index (aa-IPI) 2–3), had a dismal prognosis if treated with conventional chemotherapy. The introduction of intensive regimens and the addition of monoclonal antibody anti-CD20, improved prognosis, but some issues remain unresolved such as: the risk of central nervous system (CNS) relapses and the incidence of late toxicities. We analyzed a series of young DLBCL patients at high-risk consecutively treated in four prospective trials by the Italian Lymphoma Foundation (FIL) with the aim to assess the risk of CNS relapses and late toxicities in this series of patients with a prolonged follow-up Methods. From 1986 to 2006, 278 patients with DLBCL with aa-IPI 2–3 at diagnosis, were enrolled in four consecutive trials previously reported. Thirty-two into a phase II study, treated with 12 weekly infusion of MACOP-B; 39 into a phase II trial with eight weekly MACOP-B infusions followed by high-dose cytarabine, mitoxantrone and dexamethasone (MAD) plus standard BEAM and autologous stem cell transplantation (ASCT); 95 in a phase III trial that randomized high-dose sequential (HDS) chemotherapy plus ASCT (45 patients) vs six courses of dose-dense intensified CHOP (iCHOP) (50 patients); 112 into a phase II trial with four courses of iCHOP in combination with Rituximab followed by Rituximab-MAD + BEAM and ASCT. CNS prophylaxis was not mandatory in the four protocols. Updated data regarding of survival, CNS relapses and late toxicities were recorded on June 2011. Results. Clinical characteristics were: aa-IPI 2 in 55%, aa-IPI 3 in 45%, PS > 2 in 66%, LDH upper normal value in 89%, number of extranodal sites > 2 in 35%, bone marrow involvement in 27% of patients, with no statistical differences between the four trials. With a median follow-up of five years, 5-year Overall Survival (OS) was 63% (95% CI: 57–69%) in the whole series; 5-year OS by treatment was 41% (95%CI: 24–74%) in MACOPB, 54% (95%CI: 37–68%) in MACOPB+MAD+BEAM and ASCT; 53% (95%CI: 38–67%) in HDS+ASCT; 58% (95%CI: 43–70%) in iCHOP; 79% (95%CI: 70–86%) in R-iCHOP+R-MAD+BEAM and ASCT. In a multivariate analysis, the risk of death was significantly reduced in R-iCHOP+R-MAD+BEAM and ASCT (p<.001) and was adversely influenced by age with a progressive increase of five years at diagnosis (p.008) or aa-IPI3 (p.001). Four patients experienced CNS relapses, three of them in R-iCHOP+R-MAD+BEAM and ASCT and one in MACOPB. Only one of the four patients received CNS prophylaxis with intrathecal Methotrexate, even if all of them were at risk for CNS relapse according to Italian Society of Hematology guidelines (Barosi, Hematol 2006). Cumulative incidence of CNS recurrence at 10 years for R-iCHOP+R-MAD+BEAM and ASCT regimen was 3.6% (0 to 7.8). Most frequent late toxicities were dyslipidemia and secondary amenorrhea. Regarding to secondary malignancies, myelodisplasia or acute myeloid leukemia were recorded in three patients, two of them treated with R-iCHOP+R-MAD+BEAM and ASCT, at a median time of seven years off therapy. The actuarial risk of secondary malignancies at 10 years for R-iCHOP+R-MAD+BEAM and ASCT was 4.2% (0 to 10). Conclusions. The addition of Rituximab to dose-dense iCHOP plus high-dose chemotherapy plus BEAM and ASCT improved the outcome in young untreated DLBCL patients at poor prognosis, with an acceptable risk of secondary malignancies and late toxicities. A careful identification of patients at risk could avoid the risk of CNS relapse. Disclosures: Vitolo: Roche Italy: Speakers Bureau; Celgene: Speakers Bureau; Jannsen-Cilag: Speakers Bureau.

A Phase II Trial of Radioimmunotherapy-Based Autologous Transplantation with I-131 Tositumomab, Cyclophosphamide and Etoposide in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5502-5502
Author(s):  
Paul S Martin ◽  
Isaac C Jenkins ◽  
Theodore A Gooley ◽  
Damian J Green ◽  
John M Pagel ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Trial ◽  
Reference Group ◽  
B Cell Lymphoma ◽  
Survival Outcomes ◽  
P Value ◽  
Cox Models ◽  
Kaplan Meier

Abstract PURPOSE: Autologous stem cell transplantation (ASCT) is the standard of care for patients with chemosensitive relapsed or refractory diffuse large B-cell lymphoma (DLBCL). However, even with this aggressive approach, 40-70% of patients will still relapse. Many conventional conditioning regimens employ a combination of chemotherapy +/- total body irradiation (TBI), with further dose escalation limited by non-hematological toxicities. CD20-targeted radioimmunotherapy (RIT) delivers high doses of tumor-localized radiation with relative sparing of vital organs and has been successfully utilized to improve the efficacy and reduce the normal organ toxicity of ASCT. Based on the radiosensitivity of DLBCL and the reduced cross-resistance with chemotherapy, we hypothesized that RIT-based ASCT would improve survival outcomes for patients with relapsed/refractory DLBCL. PATIENTS AND METHODS: We performed a prospective phase II trial utilizing RIT-based myeloablative conditioning with high-dose I-131 tositumomab (to deliver ≤25 Gy to critical normal organs), cyclophosphamide (100mg/kg) and etoposide (60mg/kg) followed by ASCT in patients with relapsed/refractory DLBCL. Additionally, based on retrospective chart review, we identified and evaluated 61 eligibility-matched control patients who underwent myeloablative conditioning with TBI (12Gy), cyclophosphamide (100mg/kg), and etoposide (60mg/kg) at our Center during the trial enrollment period. RESULTS: From October 1999 to May 2011, we treated 27 DLBCL patients on this phase II trial. Baseline patient characteristics included advanced disease (89%), IPI≥2 (52%), and a median age of 51.4 years (range 31.9-59.1). The vast majority of patients had received prior rituximab (89%), with 59% considered rituximab refractory (defined as less than partial remission (PR) following or relapse within 6 months of rituximab therapy) and 55% experiencing relapse within 12 months of rituximab-based immunochemotherapy (R-chemo). Fifteen percent of patients achieved complete remission (CR) with their last chemotherapy regimen, 37% achieved PR, 26% had stable disease (SD) and 22% had progressive disease (PD). Patients received a median I-131 activity of 540 mCi (range 285 to 797), with lung (n=21), liver (n=4), and kidney (n=2) as the critical normal organs receiving the highest absorbed dose. Engraftment of neutrophilsand platelets occurred at a median of 13 (range 9-17) and 11 (range 7-38) days after ASCT, respectively. The 100-day non-relapse mortality was 7% (n=2), with one death due to cardiac failure and one due to respiratory failure. With a median follow up of 6.6 years (range 0.2-15.5), median overall survival (OS) was not reached and median progression free survival (PFS) was 3.5 years. Median PFS in the highest-risk patients, as defined by recurrent disease within 12 months of R-chemo (n=15) or chemorefractory relapse (n=13), was 22.6 and 10.8 months, respectively. Serial annual bone marrow evaluations did not identify any cases of treatment-associated myelodysplastic syndrome or acute myeloid leukemia. In comparison to the RIT group, the 61 eligibility-matched, TBI-conditioned control group patients were less heavily pretreated (2 vs 3 average prior regimens [p=<0.001], 9 vs 11 average prior cycles of chemotherapy [p=0.01]), with a trend toward higher CR rate (34% vs. 15 %, p=0.07) and lower rate of PD (9% vs. 22%, p=0.06) prior to ASCT. Adjusting for these disparate covariates, RIT-based ASCT resulted in significantly improved survival outcomes for patients with high-risk disease (relapse within 12 months of R-chemo, rituximab refractory disease, or chemorefractory relapse [SD/PD to last salvage regimen]) when compared to standard TBI-based conditioning (Figure 1). CONCLUSION: These data suggest that myeloablative RIT-based conditioning using I-131-tositumomab, cyclophosphamide and etoposide followed by ASCT is safe, feasible and effective for relapsed/refractory DLBCL. In comparison to standard TBI-based conditioning, this RIT-based approach may yield improved survival outcomes for a subset of high-risk patients. Figure 1. Kaplan-Meier curves for RIT vs TBI-based conditioning for high-risk DLBCL patients. Results from Cox models: HR = hazard ratio (95% CI) where reference group is TBI; p = p-value. Figure 1. Kaplan-Meier curves for RIT vs TBI-based conditioning for high-risk DLBCL patients. Results from Cox models: HR = hazard ratio (95% CI) where reference group is TBI; p = p-value. Disclosures Maloney: Juno Therapeutics: Research Funding; Janssen Scientific Affairs: Honoraria; Seattle Genetics: Honoraria; Roche/Genentech: Honoraria. Cassaday:Seattle Genetics: Research Funding; Pfizer: Research Funding. Gopal:Pfizer: Consultancy, Research Funding; Janssen: Consultancy; BMS: Research Funding; Sanofi-Aventis: Honoraria; Millenium: Honoraria, Research Funding; BioMarin: Research Funding; Emergent/Abbott: Research Funding; Piramal: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria; Gilead: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding.

Updated results of a phase II trial of brentuximab vedotin combined with R-CHOP in frontline treatment of patients (pts) with high-intermediate/high-risk diffuse large B-cell lymphoma (DLBCL).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 8506-8506 ◽  
Author(s):  
Nancy L. Bartlett ◽  
Charles M. Farber ◽  
Christopher A. Yasenchak ◽  
Stephen Maxted Ansell ◽  
Ranjana H. Advani ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Brentuximab Vedotin ◽  
Large B Cell Lymphoma ◽  
Frontline Treatment ◽  
Large B Cell

Weekly paclitaxel versus ADT alone in localized high-risk prostate cancer: Results of a single-institution phase II trial.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 37-37 ◽  
Author(s):  
Carolina Saldana ◽  
Laurent Salomon ◽  
Benoit Rousseau ◽  
Marie Chaubet-Houdu ◽  
Charlotte Joly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Negative Impact ◽  
Disease Free Survival ◽  
Weekly Paclitaxel ◽  
High Risk Prostate Cancer ◽  
Psa Relapse ◽  
Risk Prostate Cancer

37 Background: Adjuvant chemotherapy’s role after radical prostatectomy (RP) remains controversial in localized high-risk prostate cancer (HRPC). This phase II trial assessed the combination of weekly paclitaxel (WP) with androgen deprivation therapy (ADT) in this population. Methods: All eligible patients (pts) had undergone a laparoscopic RP with pelvic lymph node dissection for a localized HRPC defined with ≥1 of the following criteria: T3b-T4 post-operated Gleason score (GS) ≥8, PSA≥ 20 ng/mL, pN+, in Henri Mondor Hospital. Pts were randomly assigned to either triptoreline 11.25mg every 3 months during 3 years and 8 cycles of WP 100 mg/ m2 (WP arm, n=21) or triptoreline alone (ADT arm, n=26). The primary endpoint is disease free survival (DFS); events=PSA relapse, clinical and radiographic relapse, death. The planned number of pts was 152. Toxicity results indicated a good tolerability with neutropenic fever in 4.3% (n=1), and no negative impact on QoL in the WP arm (Ploussard, Prostate Cancer Prostatic Dis. 2010). Here we report 8-year DFS and overall survival (OS) results. Results: Between February 2005 and October 2007, 47 pts were enrolled. This trial was terminated prematurely because of slow accrual. After a mean follow-up of 8.4 y, we identified a PSA relapse in 25 pts (53%) and castrate-resistant prostate cancer occurred in 6 pts. No statistically difference was found in terms of either biochemical or clinical DFS (bDFS, cDFS) and OS: 8-year bDFS rate: 50% [n=11/22] in the WP arm vs 46% [n=12/26] in the ADT arm (p=0.79); 8-year cDFS rate: 95.4% [n=21/22] in the WP arm vs 88.5% [n=23/26] in the ADT arm (p=0.38). The 8-year OS rate is 90.9% (n=20/22) and 84.6% (n=22/26) respectively with no difference between treatment arms (p=0.51). No clinical, histological or biological variable demonstrated a difference in either 8-year bDFS, cDFS or OS rate. Conclusions: Provided that this trial is probably underpowered to detect a DFS benefit, adjuvant weekly paclitaxel after RP was not associated with any significant reduction in the risk of biological relapse or death compared to ADT alone in patients with localized HRPC. Chemotherapy should be only proposed in dedicated clinical trial for localized HRPC.

Phase II Trial of Initial Safety and Toxicity Prior to the Phase III Trial of Lenalidomide Versus Observation Alone in Patients with Asymptomatic High-Risk Smoldering Multiple Myeloma (E3A06): A Trial Coordinated by the Eastern Cooperative Oncology Group

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4079-4079 ◽  
Author(s):  
Sagar Lonial ◽  
Susanna Jacobus ◽  
Matthias Weiss ◽  
Rafael Fonseca ◽  
Madhav V. Dhodapkar ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Research Funding ◽  
Plasma Cells ◽  
Phase Ii Trial ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Trial Testing ◽  
Grade 3 ◽  
Smoldering Myeloma

Abstract Abstract 4079 The treatment and natural history of asymptomatic or smoldering myeloma has been an area of intense preclinical and clinical study. Historical attempts to treat these patients have not demonstrated significant benefit, likely as a consequence of limited therapeutic options as well lack of attention to the vast heterogeneity contained within the diagnosis of smoldering myeloma. More recent risk criteria from both US and Spanish investigators have identified a cohort of smoldering myeloma patients at high risk for progression to myeloma in a short time. Recently the PETHEMA group has conducted a randomized clinical trial testing lenalidomide and dexamethasone vs observation among high risk smoldering patients and has demonstrated a clear benefit in terms of progression free survival and hints towards improvement in overall survival favoring early intervention. To further evaluate the potential benefit of early intervention in a high risk smoldering cohort, the ECOG myeloma group designed a phase II trial testing the safety and efficacy of single agent lenalidomide with the intent of broadening to a randomized phase III trial if toxicity was acceptable. We report here on the safety portion of the phase II trial. The phase II group of patients received lenalidomide at a dose of 25 mg days 1–21 every 28 days to evaluate the early toxicity and tolerance of this dosing. The dose of lenalidomide could be adjusted based on toxicity using a defined dose-modification guideline in the protocol. The primary endpoint for the safety study was the rate of any treatment-related grade 4–5 non-hematologic toxicity plus grade 3 non-hematologic toxicity that affects vital organ function (such as cardiac, hepatic, or thromboembolic events) observed within 6 cycles of treatment. The goal was to enroll 34 patients; if 9 or more patients experience toxicity as defined, then the study would not continue. In terms of eligibility, patients were to be diagnosed with asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 12 months, as confirmed by both of the following: bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells and an abnormal serum free light chain ratio (<0.125 or >8.0) by serum FLC assay. Further, patients must have measurable levels of monoclonal protein (M-protein): >=1g/dL on serum protein electrophoresis or >=200 mg of monoclonal protein on a 24 hour urine protein electrophoresis. Patients must have no lytic lesions on skeletal surveys and no hypercalcemia. Among the 36 patients enrolled in the phase II study, 56% were female, and 44% were 65 years and older. Treatment and toxicity data at a minimum through cycle 6 is complete as of August 2, 2102. The last patient enrolled completed cycle 6 treatment on June 7, 2012. The median treatment duration of the entire cohort is 9 cycles (range 1–18 cycles), with 86% of patients completing at least 6 cycles of treatment. Ten patients are off treatment for the following reasons: disease progression (n=1), AE/complication (n=5), death (n=1) and patient withdrawal/refusal (n=3); 5 of the 10 patients ended treatment before completing 6 cycles. Of 36 patients assessed for toxicity, 8 patients [22.2%, 90% CI: (11.6%-36.5%)] experienced worst grade treatment-related non-hematologic toxicity of grade 3 or higher. Separately, 6 patients experienced unrelated non-hematologic toxicity of grade 3 or higher. Three patients [8.3%, 90% CI: (2.3%-20.2%)] experienced a serious adverse event as defined for the purposes of the phase II toxicity analysis (treatment-related grade 4–5 non-hematologic toxicity or grade 3 non-hematologic toxicity that affects vital organ function (such as cardiac, hepatic, or thromboembolic events). Based upon this analysis of the study, the phase II portion of the trial met the prespecified safety benchmark established to allow for phase III expansion, and accrual to the phase III portion of this study will begin. Efficacy data will be presented at the time of presentation. Disclosures: Lonial: Novartis: Consultancy; Millennium: Consultancy; Onyx: Consultancy; BMS: Consultancy; Celgene Corp: Consultancy; Merck: Consultancy. Off Label Use: Lenalidomide is not approved for treatment of smoldering MM. Fonseca:Medtronic: Consultancy; Otsuka: Consultancy; Celgene: Consultancy; Genzyme: Consultancy; BMS: Consultancy; Lilly: Consultancy; Onyx: Consultancy; Binding site: Consultancy; Millenium: Consultancy; AMGEN: Consultancy; Celgene : Research Funding; Onyx: Research Funding; prognostication of MM based on genetic categorization of the disease: Prognostication of MM based on genetic categorization of the disease, Prognostication of MM based on genetic categorization of the disease Patents & Royalties. Dhodapkar:Celgene: Research Funding; KHK: Research Funding.

Phase II Trial of Biweekly Chemotherapy with Docetaxel and Cisplatin in High-Risk Patients with Unresectable Non-Small Cell Lung Cancer

Chemotherapy ◽  
2013 ◽  
Vol 59 (3) ◽  
pp. 159-166 ◽  
Author(s):  
Moon Jin Kim ◽  
Seok-Hyun Kim ◽  
Jung Hun Kang ◽  
Hoon Gu Kim ◽  
Yu Ji Cho ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Trial ◽  
Small Cell ◽  
Small Cell Lung ◽  
High Risk Patients ◽  
Risk Patients

The adjuvant role of low dose total body irradiation following chemoimmunotherapy in elderly high risk patients with diffuse large B-cell lymphoma (DLBCL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17523-17523
Author(s):  
A. Safwat ◽  
L. Specht ◽  
F. Hansen ◽  
M. Hansen ◽  
A. Boesen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
High Risk ◽  
Total Body Irradiation ◽  
Low Dose ◽  
B Cell Lymphoma ◽  
Relative Increase ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Total Body

17523 Background: Results from the RICOVER-60 trial indicated a better outcome in elderly DLBCL patients (pts) by adding rituximab (R) to CHOP and shortening cycle intervals 14 days. We tested the addition of low dose total body irradiation (LTBI) to what proved to be the best performing arm of the RICOVER-60 trial (6xR-CHOP-14 + 2xR). Methods: A phase II trial including pts>60 yrs with stage II-IV, CD20-positive DLBCL was started in 2003 and is still ongoing. Pts received 6x R-CHOP-14 and 2 x R alone followed by LTBI given as 2 courses of 4 daily fractions of 0,2 Gy separated by 2 weeks of rest. Subpopulations of blood lymphocytes, monoctytes and dendritic cells were identified by multi-color flowcytometry during treatment. Results: 24 patients finished their treatment and were found to be predominantly high risk. Median age was 68 years; 50% had ≥ 1 extranodal lesion; 71% had stage III or IV; 63% had B symptoms; 58% had ECOG score ≥ 1; 75% had elevated LDH and 58% had IPI of >2. There were 3 toxic deaths (12.5%) due to sepsis occurring after 1st, 3rd and 5th chemotherapy cycle, respectively. One patient got off study because of disease progression. 14 pts achieved a CR or CRu at the end of chemotherapy, while 6 were in PR. After LTBI, all 6 PR pts converted to CR. 3 pts relapsed within 7 months after achieving CR. All treatment failures occurred in patients with IPI 3&4. 94%, 100% and 98% of the administered R-CHOP-14, Rituximab and LTBI cycles respectively were given in full dose and on time. CTC Gr 3–4 neutropenia occurred following 22 of 135 R-CHOP-14 cycles (16%). CTC Gr. 3–4 thrombocytopenia was seen in 4 pts following the last LTBI cycle (16%). Preliminary data from multi-color flowcytometry of the first seven pts, showed depletion of circulating B-cells, but in some pts, a relative increase in the frequency of circulating dendritic cells during chemotherapy, which was enhanced by LTBI. Conclusion: In high-risk elderly DLBCL pts, R-CHOP-14 is associated with potential fatal infections. LTBI adds relatively little extra toxicities in the form of thrombocytopenia and may have the potential of converting PR patients to CR. Testing lymphocytic subpopulations in peripheral blood may help elucidating the immunomodulatory mechanisms of LTBI. No significant financial relationships to disclose.

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