Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab (Rituxan®) and Lenalidomide (Revlimid®) in Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

NCT01754870 | Withdrawn Phase 2 DMC

• 5 other identifiers: HO114152012-0639A534260SMPH/MEDICINE/MEDICINE*HNCI-2013-00905
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

CLL/SLL is an incurable disease with conventional chemotherapy, and there are limited treatment options available for patients who have become refractory to fludarabine- and alkylating-agent based regimens. Bendamustine is a recently FDA-approved agent with significant activity in CLL/SLL, including significant activity in the setting of fludarabine-refractory disease. However, durations of remission following bendamustine/rituximab combination therapy tend to be short in patients with heavily pre-treated disease or who have already received rituximab. The incorporation of a maintenance therapy to overcome the shorter remission durations in this population is a reasonable and feasible option. In considering potential options for treatment of CLL/SLL as a maintenance strategy following induction chemotherapy, lenalidomide and rituximab are appealing options based on their convenient dosing schedules and recent evidence of acceptable toxicity and promising efficacy in combination therapy.

Conditions

Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)

Keywords

CLL; SLL

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  • The primary objective is progression-free survival for patients entering the maintenance therapy phase with rituximab and lenalidomide after induction therapy with bendamustine and rituximab. Progression is defined as radiographic or clinical progression as defined by the specified standard response criteria for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)or initiation of a new anti-neoplastic therapy in the absence of progression. Subjects with clinical evidence of progression prior to a planned disease assessment will be evaluated at the time of clinically suspected progression.

  Up to 30 months

Secondary Outcomes (3)

• Objective Response Rates

  Up to 30 months

• Toxicity

  Up to 30 months

• Overall survival

  Up to 54 months

Study Arms (1)

Bendamustine + Rituximab-->Rituximab and Lenalidomide

EXPERIMENTAL

Induction chemoimmunotherapy: * Bendamustine 70 mg/m2 IV days 1 \& 2 every 28 days X 6 cycles * Rituximab 500 mg/m2 IV day 1 every 28 days X 6 cycles (375 mg/m2 IV cycle 1 only, day 1 or 2) Maintenance phase: * Rituximab 375 mg/m2 IV on day 1 of every odd-numbered 28 day cycle for a maximum of 12 doses during the maintenance phase. * Lenalidomide 5 mg orally daily on days 1-28 of each 28-day cycle for 24 cycles (maintenance cycles 1-24); dose escalation to 10 mg orally daily will be allowed at the start of cycle 2 or at the start of any subsequent cycle in subjects with acceptable toxicities needed to escalate the dose of lenalidomide to 10 mg/day.

Drug: Bendamustine and Rituximab Induction followed by Rituximab and Lenalidomide Maintenance

Interventions

Bendamustine and Rituximab Induction followed by Rituximab and Lenalidomide Maintenance DRUG

Bendamustine + Rituximab-->Rituximab and Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed CLL/SLL.
• Understand and voluntarily sign an informed consent document.
• Age greater than or equal to 18 years at the time of signing the informed consent document.
• Subjects must have documented relapsed or refractory CLL/SLL.
• Relapsed disease is defined as progressive disease after achieving a complete or partial response to the most recent therapy.
• Refractory disease is defined as less than a partial response to the most recent therapy.
• Subjects must have received ≥1 prior chemotherapy regimen for their disease. Prior therapy with single-agent rituximab does not meet criteria for a prior chemotherapy regimen (i.e., prior treatment must include cytotoxic chemotherapy agent).
• In cases of SLL, subjects must have at least one bidimensionally measurable lesion at least ≥1.5 cm measured in one dimension.
• Eastern Cooperative Oncology Group performance status of less than or equal to 2 at study entry
• Laboratory test results within these ranges:
• Absolute neutrophil count greater than or equal to 1500/μL
• Platelet count great than or equal to 100,000/μL
• Subjects with neutrophils \<1500/μL or platelets \<100,000/μL with splenomegaly or extensive bone marrow involvement as the etiology for their cytopenias are eligible
• Subjects must have adequate renal function with a creatinine clearance of ≥40 mL/min as determined by the Cockcroft-Gault calculation
• Total bilirubin less than or equal to 2X (times) upper limit laboratory normal (ULN); subjects with non-clinically significant elevations of bilirubin due to Gilbert's disease are not required to meet these criteria

You may not qualify if:

• Subjects may not have received \>5 lines of prior therapy for their disease. Re-treatment with an identical regimen does not count as a new regimen.
• \. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document or complying with the protocol treatment.
• \. Pregnant or breast-feeding females. Lactating females must agree not to breast-feed while taking lenalidomide.
• \. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• \. Subjects are not eligible if there is a prior history or current evidence of central nervous system or leptomeningeal involvement.
• \. Use of any other experimental drug or therapy within 28 days of enrollment.
• \. Known hypersensitivity to thalidomide. 8. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• \. Disease that is refractory to prior therapy with bendamustine or lenalidomide.
• \. Concurrent use of other anti-cancer agents or treatments. 11. Known to be positive for HIV or infectious hepatitis (type B or C). 12. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, or other cancer from which the subject has been disease free for at least 2 years.
• \. Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously exposed to rituximab or other monoclonal antibody therapy.
• \. Chronic hepatitis B or hepatitis C infection. 15. New York Heart Association class 3-4 heart failure.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Celgene Corporation: collaborator
• Genentech, Inc.: collaborator

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Julie Chang, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2012
• First Posted: December 21, 2012
• Study Start: November 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: November 15, 2019

Record last verified: 2015-07