A Study Comparing Rituximab/Bendamustin(RB) Alternating With Rituximab/Bendamustin/Cytarabin(RBAC) With RB Therapy in Elderly Patients With Mentle Cell Lymphoma

Study Overview
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Brief Summary
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This is a phase 2, multicenter, open-label, active-controlled randomized trial to determine efficacy and safety of rituximab/bendamustine (RB) alternating with rituximab/bendamustine/cytarabine (RBAC) compared with standard RB alone in the first-line treatment of elderly patients with mantle cell lymphoma, who are not eligible for high-dose therapy followed by autologous stem cell transplantation.

Detailed Description
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Eligible patients will be randomly assigned to either the investigational treatment arm (RB alternating with RBAC) or the standard treatment arm (RB) in a 1:1 ratio. Patients will be stratified by age (≥70 years vs. 60-69), histologic morphology (blastoid/pleomorphic vs. non-blastoid/non-pleomorphic), and MIPI-C risk score (0/1 vs. 2/3).

Official Title
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A Randomized Phase II Trial Comparing Rituximab/Bendamustine(RB) Alternating With Rituximab/Bendamustine/Cytarabine(RBAC) With RB as Induction Therapy in Elderly Patients With Newly Diagnosed and Transplant-ineligible Mantle Cell Lymphoma

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: RB/RBAC alternating
* Drug: RB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed, previously untreated, histologically confirmed CD20+ mantle cell lymphoma, confirmed by WHO classification criteria age ≥70 years or 60-69 years if the patients are ineligible for high-dose therapy with autologous stem cell transplantation. ECOG performance status 2 or less Adequate organ functions adequate heart function: LVEF ≥50% by echocardiography or MUGA adequate renal function: serum creatinine ≤ 2.0mg/dL or CrCl ≥40 mL/min based on the Cockcroft-Gault method adequate hepatic function: ≤2.5 times the upper limit of ALT (≤5 times the upper limit of ALT if the elevation is attributed by underlying lymphoma) and ≤2 times the upper limit of ALT (≤3 times the upper limit of total bilirubin if the elevation is attributed by underlying lymphoma) adequate hematologic function: absolute neutrophil counts (ANC) ≥ 1,500/mL, platelet counts ≥ 100,000/mL (any ANC and platelet counts are allowed, if they were related to bone marrow involvement) Written informed consent Exclusion Criteria: In-situ mantle cell lymphoma Ann Arbor stage 1 disease Prior treatment for Hodgkin lymphoma or non-Hodgkin lymphoma within the last 5 years. Active malignancy within the past 3 years except for localized non-melanoma skin cancer, papillary thyroid cancer, cervical carcinoma in situ, breast cancer in situ, or localized prostate cancer that has been definitely treated, Central nervous system involvement HBsAg (+) or anti-HBc Ab (+) (patients will be eligible if they receive appropriate prophylactic antiviral therapy using entecavir, tenofovir, and so on) History of prior hepatitis C infection (patients positive for HCV IgG will be eligible if they are negative for HCV-RNA) Known history of human immunodeficiency virus (HIV) infection any serious illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study Congestive heart failure ≥ NYHA class 3 Acute coronary syndrome within 6 months (unstable angina or new-onset angina, myocardial infarct, or ventricular arrhythmia) History of significant neurological or psychological disorder including dementia and seizure disorder Severe chronic obstructive pulmonary disease with hypoxemia Cerebrovascular disease including transient ischemic attack within the past 6 months Non-healing wound, ulcer, or bone fracture Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy concomitant administration of any other experimental drugs under investigation Known hypersensitivity to bendamustine, rituximab, cytarabine, or mannitol major surgical procedure or significant trauma within 28 days before start of study treatment, open biopsy within 7 days before start of study treatment If the patient's partner is a woman who could possibly get pregnant, men who didn't have a vasectomy must agree to use medically recommended methods for adequate contraception (tubal ligation, intrauterine devices, or barriers [diaphragm, cervical cap] in the patient's partner and the use of condoms in men) when sexually active.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RB/RBAC alternating<br>Every 4 weeks for 6 cycles RB (1st, 3rd, and 5th cycles) Rituximab + Bendamustine RBAC (2nd, 4th, and 6th cycles) Rituximab + Bendamustine + Cytarabine | Drug: RB/RBAC alternating<br>* Patients assigned to the RB alternating with RBAC arm will receive six cycles of alternating RB (odd cycles) or RBAC (even cycles) RB (1st, 3rd, and 5th cycles) Rituximab 375mg/m2, IV, D1 Bendamustine 90mg/m2, IV, D1-2 RBAC (2nd, 4th, and 6th cycles) Rituximab 375mg/m2, IV, D1 Bendamustine 70mg/m2, IV, D2-3 Cytarabine 500mg/m2, IV, D2-4<br>|
| Active Comparator: RB<br>Every 4 weeks for 6 cycles - Rituximab + Bendamustine | Drug: RB<br>* Every 4 weeks for 6 cycles Rituximab 375mg/m2, IV, D1 Bendamustine 90mg/m2, IV, D1-2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-freesurvival |  | Up to 84 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | Up to 84 months | 
| Duration of Response |  | Up to 84 months | 
| Event Free Survival |  | Up to 84 months | 
| Overall response rate |  | Up to 84 months | 
| Adverse events |  | From the day 1 of the clinical trial to 28 days after last drug administration |