NCT01415752|Active Not RecruitingPhase 2ResultsDMCFDA Drug

Rituximab, Bendamustine Hydrochloride, and Bortezomib Followed by Rituximab and Lenalidomide in Treating Older Patients With Previously Untreated Mantle Cell Lymphoma

Intergroup Randomized Phase 2 Four Arm Study In Patients ≥ 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB → R); Arm B = Rituximab + Bendamustine + Bortezomib Followed By Rituximab Consolidation (RBV→ R), Arm C = Rituximab + Bendamustine Followed By Lenalidomide + Rituximab Consolidation (RB → LR) or Arm D = Rituximab + Bendamustine + Bortezomib Followed By Lenalidomide + Rituximab Consolidation (RBV → LR)

Eastern Cooperative Oncology Group ClinicalTrials.gov

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3 other identifiers

E1411NCI-2011-02980CDR0000707057

Study Type

interventional

Target

373

Locations

2 countries

Sites

418

Timeline

RegisteredAug 2011

StartedAug 2012

CompletionSep 2031

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma. PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

373

participants targeted

Target at P75+ for phase_2 lymphoma

Timeline

64mo left

Started Aug 2012

Longer than P75 for phase_2 lymphoma

Geographic Reach

2 countries

418 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

19.1 years study duration

Study Progress72%

Aug 2012Sep 2031

First Submitted

Initial submission to the registry

August 11, 2011

Completed

1 day until next milestone

First Posted

Study publicly available on registry

August 12, 2011

Completed

12 months until next milestone

Study Start

First participant enrolled

August 9, 2012

Completed

10.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 25, 2023

Completed

2.1 years until next milestone

Results Posted

Study results publicly available

April 8, 2025

Completed

6.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2031

Expected

Last Updated

April 8, 2025

Status Verified

March 1, 2025

Enrollment Period

10.6 years

First QC Date

August 11, 2011

Results QC Date

February 14, 2025

Last Update Submit

April 7, 2025

Conditions

Lymphoma Mantle Cell Lymphoma

Keywords

LymphomaMantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

Progression-free Survival (PFS) for Induction Phase
PFS is defined as time from randomization to lymphoma progression or death. Progression is defined as: * Appearance of any new lesion \>1.5 cm in any axis during or at the end of therapy * \>=50% increase from nadir in the sum of products of the diameters (SPD) of any previously involved nodes or extranodal masses, or in a single involved node or extranodal mass, or the size of other lesions. * \>=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis. * Lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was PET positive before therapy unless the lesion is too small to be detected with current PET systems
Assessed at baseline, every 3 months for 2.5 years, every 6 months up to 10 years from end of treatment, and then annually up to 10 years and 6 months
Progression-free Survival (PFS) for Maintenance Phase (Step 2)
PFS is defined as time from Step 2 registration to lymphoma progression or death. Progression is defined as: * Appearance of any new lesion \>1.5 cm in any axis during or at the end of therapy * \>=50% increase from nadir in the sum of products of the diameters (SPD) of any previously involved nodes or extranodal masses, or in a single involved node or extranodal mass, or the size of other lesions. * \>=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis. * Lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was PET positive before therapy unless the lesion is too small to be detected with current PET systems
Assessed at registration to step 2, cycles 6, 12, 18, treatment completion, then every 3 months for 2.5 years, every 6 months up to 10 years from end of treatment, and then annually up to 10 years and 6 months

Secondary Outcomes (4)

Objective Response for Induction Phase (Step 1)
Assessed at baseline and 24 weeks (end of cycle 6)
PET-documented Complete Response for Induction Phase (Step 1)
Assessed at baseline and 24 weeks (end of cycle 6)
Overall Survival (OS) Rate at 5 Years Since Maintenance (Step 2)
Assessed every 3 months for 2.5 years, every 6 months for years 2.5-5
Objective Response for Maintenance (Step 2) Among Patients Without PET-documented CR at the End of Induction
Assessed at baseline and every 4 months for 2 years

Other Outcomes (20)

To Collect Paraffin Embedded Tissue for Creation of Tissue Microarray
Assessed at baseline
To Collect and Bank Serum and Blood Mononuclear Cells for Future Studies
Assessed at baseline, end of cycle 3, end of cycle 6, every 4 months during first year of maintenance, every 6 months during 2nd year of maintenance, and 12 months after completion of maintenance
To Collect Formalin Fixed Paraffin Embedded (FFPE) Tissue to Analyze Potential Prognostic Factors
Assessed at baseline
+17 more other outcomes

Study Arms (4)

Induction: (A) Bendamustine + Rituximab then Maintenance: (E) Rituximab

EXPERIMENTAL

Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Biological: rituximabDrug: Bendamustine

Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) Rituximab

EXPERIMENTAL

Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Biological: rituximabDrug: BendamustineDrug: bortezomib

Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + Rituximab

EXPERIMENTAL

Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Biological: rituximabDrug: BendamustineDrug: lenalidomide

Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab

EXPERIMENTAL

Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Biological: rituximabDrug: BendamustineDrug: bortezomibDrug: lenalidomide

Interventions

rituximabBIOLOGICAL

Given IV

Also known as: IDEC-C2B8, Chimeric anti-CD20 monoclonal antibody, Rituxan

Induction: (A) Bendamustine + Rituximab then Maintenance: (E) RituximabInduction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) RituximabInduction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + RituximabInduction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab

BendamustineDRUG

Given IV

Also known as: bendamustine hydrochloride, CEP-18083, TREANDA, BENDEKA

bortezomibDRUG

Given IV or SC

Also known as: MLN341, LDP-341, Velcade®

Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) RituximabInduction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab

lenalidomideDRUG

Given PO

Also known as: IMiDTM compound CC-5013, Revlimid®

Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + RituximabInduction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab

Eligibility Criteria

Age18 Years - 120 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Mantle Cell Lymphoma International Prognostic Index (MIPI) score must be calculated and entered in OPEN
Histologically confirmed untreated mantle cell lymphoma (MCL), with documented cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH)
Patients must have at least one objective measurable disease parameter
Negative pregnancy test
Women of childbearing potential and sexually active males use an accepted and effective method of contraception
ECOG performance status 0-2
Absolute neutrophil count (ANC) ≥ 1,500/mcL (1.5 x 10\^9/L)
Platelets ≥ 100,000/mcL (100 x 10\^9/L)
Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2 times upper limit of normal (ULN)
Bilirubin ≤ 2 times ULN
Calculated creatinine clearance by Cockroft-Gault formula ≥ 30 mL/min
Patient agrees that if randomized to Arms C or D, and proceeding onto Arms G or H, they must register into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist. Patients must have no medical contra-indications to, and be willing to take, DVT prophylaxis as all patients registering to the lenalidomide/rituximab Arms G and H will be required to have deep vein thrombosis (DVT) prophylaxis. Patients randomized to Arms G or H who have a history of a thrombotic vascular event will be required to have full anticoagulation, therapeutic doses of low molecular weight heparin or warfarin to maintain an INR between 2.0 - 3.0, or any other accepted full anticoagulation regimen (e.g. direct thrombin inhibitors or Factor Xa inhibitors) with appropriate monitoring for that agent. Patients on Arms G and H without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis. Patients who are unable to tolerate aspirin should receive low molecular weight heparin therapy or warfarin treatment or another accepted full anticoagulation regimen. Ways to minimize risk of DVT should be discussed with patients, including, but not limited to, avoiding smoking, minimizing prothrombotic hormone replacement, avoiding prolonged periods of inactivity (e.g. uninterrupted long car or plane trips).
HIV-positive patients are not excluded but, to enroll, must meet all of the below criteria:
HIV is sensitive to antiretroviral therapy
Must be willing to take effective antiretroviral therapy, if indicated
+3 more criteria

You may not qualify if:

Women (sexually mature female) must not be pregnant or breast-feeding
Evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma, low grade prostate carcinoma (Gleason grade ≤ 6) managed with observation that has been stable for at least 6 months, or any malignancy treated with curative intent continuously disease free for \>=3 years so as not to interfere with interpretation of radiographic response
Prior therapy for MCL, except: \< 2 weeks of steroid therapy for symptom control or local radiation therapy for symptom control if there is measurable disease outside the radiation portal. Patients may be on chronic steroids for non-malignant disease if on a stable dose equivalent to ≤ 20 mg prednisone per day.
CNS involvement
History of AIDS-defining conditions
Grade 2 or greater peripheral neuropathy.
NYHA Class III or IV heart failure, uncontrolled angina severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
Hypersensitivity to bortezomib, boron or mannitol
A serious medical or psychiatric illness likely to interfere with study participation
Participating in any other therapeutic clinical trial or taking any other experimental medications within 14 days prior to registration.
ECOG performance status between 0-2
Complete response, partial response or stable disease after Step 1
ANC \>= 1000 cells/mm3 (1.0 x 10\^9/L)
Platelets \>= 75,000 cells/mm3 (75 x 10\^9/L)
AST/ALT \<= 2 x upper limit of normal (ULN)
+11 more criteria

Contact the study team to confirm eligibility.