Rituximab/Bendamustine + Rituximab/Cytarabine for Mantle Cell Lymphoma
- Conditions
- Mantle Cell Lymphoma
- Interventions
- Registration Number
- NCT01661881
- Lead Sponsor
- Dana-Farber Cancer Institute
- Brief Summary
Mantle cell lymphoma (MCL) is not curable with conventional therapy. This study sought to improve upon standard of care in newly diagnosed, untreated MCL patients who were transplant-eligible using drugs already established as active in MCL. The combination of Rituximab-Bendamustine followed by Rituximab-Cytarabine (RB/RC) was expected to maximize pre-ASCT complete response (CR) rate compared to historical rates approximating 55% with tolerable toxicity.
- Detailed Description
This was a PII single-arm design to determine whether the regimen looked promising for further study.
Primary Objective
• To evaluate the efficacy of an alternating regimen of Rituximab-Bendamustine and Rituximab-Cytarabine (RB/RC) using the CR/Cru rate.
Secondary Objectives
* To assess safety.
* To estimate the rate of complete remission (CR), unconfirmed CR (CRu), partial remission (PR), stable disease (SD) and progressive disease (PD).
* To estimate the rate of successful stem cell mobilization after RB/RC in responding patients.
* To estimate the proportion of patients who can successfully complete the regimen and proceed to autologous stem cell transplantation (ASCT).
* To estimate the rate of neutrophil and platelet engraftment after ASCT.
* To estimate the CR/CRu and PR rate for patients with blastoid variant MCL.
* To estimate the rate of minimal residual disease (MRD)-negativity at treatment completion.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 23
- Mandatory pathologic review of the diagnostic specimen(s) at Brigham and Women's Hospital or Massachusetts General Hospital
- Measurable disease
- Candidate for ASCT
- Prior anti-lymphoma therapy
- Pregnant or breastfeeding
- Hypersensitivity to rituximab
- Uncontrolled intercurrent illness
- Receiving other study agents
- HIV positive on combination antiretroviral therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description RB/RC Rituximab Patients received 3 cycles of outpatient RB (rituximab 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2 of a 4-week cycle), followed by interim CT restaging. Patients with progressive disease (PD) went off study. Those with stable disease (SD) or better went on to receive three cycles of inpatient RC (rituximab 375 mg/m2 day 1, cytarabine 3 g/m2 every 12 h for 4 doses). The cytarabine was dose reduced to: 1. 2 g/m2 for age \>60 years old, creatinine 114.9-176.8 lmol/l (for patients ≤60 years old), and pre-existing neurotoxicity; 2. 1.5 g/m2 for age \>60 years old AND creatinine 114.9-176.8 lmol/l, or for age \>60 years old AND pre-existing neurotoxicity; 3. 1 g/m2 for age \> 60 years old AND creatinine 114.9-176.8 lmol/l AND pre-existing neurotoxicity. Stem cell mobilization and collection, ASCT and post-transplantation supportive care were performed per institutional standard and not as part of this study. RB/RC Bendamustine Patients received 3 cycles of outpatient RB (rituximab 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2 of a 4-week cycle), followed by interim CT restaging. Patients with progressive disease (PD) went off study. Those with stable disease (SD) or better went on to receive three cycles of inpatient RC (rituximab 375 mg/m2 day 1, cytarabine 3 g/m2 every 12 h for 4 doses). The cytarabine was dose reduced to: 1. 2 g/m2 for age \>60 years old, creatinine 114.9-176.8 lmol/l (for patients ≤60 years old), and pre-existing neurotoxicity; 2. 1.5 g/m2 for age \>60 years old AND creatinine 114.9-176.8 lmol/l, or for age \>60 years old AND pre-existing neurotoxicity; 3. 1 g/m2 for age \> 60 years old AND creatinine 114.9-176.8 lmol/l AND pre-existing neurotoxicity. Stem cell mobilization and collection, ASCT and post-transplantation supportive care were performed per institutional standard and not as part of this study. RB/RC Cytarabine Patients received 3 cycles of outpatient RB (rituximab 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2 of a 4-week cycle), followed by interim CT restaging. Patients with progressive disease (PD) went off study. Those with stable disease (SD) or better went on to receive three cycles of inpatient RC (rituximab 375 mg/m2 day 1, cytarabine 3 g/m2 every 12 h for 4 doses). The cytarabine was dose reduced to: 1. 2 g/m2 for age \>60 years old, creatinine 114.9-176.8 lmol/l (for patients ≤60 years old), and pre-existing neurotoxicity; 2. 1.5 g/m2 for age \>60 years old AND creatinine 114.9-176.8 lmol/l, or for age \>60 years old AND pre-existing neurotoxicity; 3. 1 g/m2 for age \> 60 years old AND creatinine 114.9-176.8 lmol/l AND pre-existing neurotoxicity. Stem cell mobilization and collection, ASCT and post-transplantation supportive care were performed per institutional standard and not as part of this study.
- Primary Outcome Measures
Name Time Method Complete Remission (CR) Rate After 6 Cycles Disease was assessed after three- and six-cycles of therapy, up to approximately 25 weeks. All patients completed 6 cycles of therapy with a cycle duration of 28 days. The CR rate is defined as the proportion of patients who after 6 cycles of therapy achieve complete remission based on the International Working Group (IWG) Criteria (Cheson et al, 1999), using CT scans. CR or CRu (CR unconfirmed) by CT scans was defined by standard IWG criteria, ie resolution of all abnormal adenopathy and organomegaly, and clearance of marrow disease when present at baseline.
- Secondary Outcome Measures
Name Time Method Autologous Stem Cell Transplant (ASCT) Rate All patients were followed for continuation to ASCT upon completion of induction therapy. Patients usually proceed to ASCT within 3 months of completing induction. ASCT rate is the proportion of patients who completed therapy and proceeded to autologous stem cell transplant (ASCT)
1 Year Progression-Free Survival Disease was assessed after three- and six-cycles of therapy and in long-term follow-up per standard practice every 6 months until the earliest of relapse, death or 5 years. Median follow-up in this study cohort was 13 months. 1-year progression-free survival is the probability of patients remaining alive and progression-free at 1 year from study entry estimated using Kaplan-Meier methods. Disease progression was based on the International Working Group (IWG) Criteria (Cheson et al, 1999).
Trial Locations
- Locations (3)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States