Bendamustine and Rituximab Induction Therapy and Maintenance Rituximab and Lenalidomide in Previously Untreated CLL/SLL

NCT01754857 | Completed Phase 2 Results DMC FDA Drug

• 6 other identifiers: HO114142017-0072A534260SMPH\MEDICINE\HEM-ONCNCI-2013-00485Protocol Version 3/1/2020
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose a treatment strategy where patients are treated with induction chemoimmunotherapy consisting of rituximab + bendamustine for 6 cycles, followed by initiation of maintenance rituximab and lenalidomide among patients achieving an objective response (i.e., at least stable disease with some tumor shrinkage) to induction therapy. The goal of maintenance therapy will be to capitalize on the cytoreduction following induction chemotherapy with a maintenance regimen that has also shown promising activity in CLL, in order to allow for improved PFS in this population.

Conditions

Lymphoid Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Non-Hodgkin

Keywords

Lymphoid Leukemia; Bendamustine; Rituximab; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Time to Progression

  The primary objective is progression-free survival (PFS). Tumor measurements and disease assessments will be performed at the time of screening, following cycles 3 and 6 of induction chemotherapy, every 4 cycles during the maintenance portion of treatment, and at the end of treatment (EOT). Subjects with clinical evidence of progression prior to a planned disease assessment will be evaluated at the time of clinically suspected progression. Follow-up visits for disease assessment will occur every 3 months after the EOT visit until PD, initiation of alternate anti-neoplastic therapy, decision by the subject to withdraw from the study, or death. The follow-up period will begin after the EOT visit, and all subjects will be followed for at least 2 years after completion of therapy or until death or progression and until the last patient has been followed for at least 1 year following completion of therapy.

  At least 24 months following completion of therapy, an average of 5 years

Secondary Outcomes (2)

• Objective Response Rates

  Up to 30 months

• Count of Events Related to Toxicity

  Up to 30 months

Study Arms (1)

Bendamustine, rituximab, lenalidomide

EXPERIMENTAL

INDUCTION: Bendamustine 90mg/m2 IV D1\&2 and rituximab IV D1 (up to day 5 of course 1) every 28 days for 6 cycles. Patients with objective response move to maintenance therapy. Patients with objective response after 4 courses are eligible to for maintenance therapy if ongoing induction therapy is associated w/unacceptable toxicity. MAINTENANCE: At 6-12 wks post induction therapy, patients receive rituximab IV on day 1 of odd-numbered cycles for 24 cycles; lenalidomide 5mg PO daily on days 1-21 of each cycle (28 day cycles). Dose escalation to 10mg daily on days 1-21 allowed at start of cycle 2 or at start of subsequent cycles in subjects w/acceptable toxicities. Lenalidomide dose escalation only allowed at start of a new cycle up to a max dose of 10 mg/day on days 1- 21. Subjects entering maintenance with CrCl ≥40 \& \<60mL/min will begin dosing at 5mg every other day on days 1-21. Patients with excessive toxicity from lenalidomide may continue maintenance therapy with rituximab alone.

Drug: Bendamustine; Drug: Rituximab; Drug: Lenalidomide

Interventions

Bendamustine DRUG

Given IV

Bendamustine, rituximab, lenalidomide

Rituximab DRUG

Given IV

Bendamustine, rituximab, lenalidomide

Lenalidomide DRUG

Given PO

Bendamustine, rituximab, 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 chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
• No prior cytotoxic chemotherapy for their disease; prior therapy with single-agent rituximab is permitted
• Understand and voluntarily sign an informed consent document
• 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 (ECOG) performance status of =\< 2 at study entry
• Absolute neutrophil count \>= 1500/uL
• Platelet count \>= 100,000/uL
• Subjects with neutrophils \< 1500/uL or platelets \< 100,000/uL 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 =\< 2 x 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
• Serum transaminases aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x ULN
• Serum alkaline phosphatase =\< 5 x ULN
• Disease-free of prior malignancies for \>= 2 years with the exception of basal or squamous cell skin carcinoma, carcinoma "in situ" of the breast or cervix, or localized prostate cancer (treated definitively with hormone therapy, radiotherapy, or surgery)
• Life expectancy of at least 3 months
• All study participants must be willing to be registered into the mandatory Revlimid REMS program after completion of induction chemoimmunotherapy and prior to maintenance therapy, and be willing and able to comply with the requirements of the Revlimid REMS program

You may not qualify if:

• 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
• Known hypersensitivity to thalidomide
• Concurrent use of other anti-cancer agents or treatments
• Known to be positive for human immunodeficiency virus (HIV) or infectious hepatitis (type B or C)
• 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
• New York Heart Association class 3-4 heart failure
• More than one grade 2 or higher transaminase elevation

Sponsors & Collaborators

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

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Chang JE, Havighurst T, Kim K, Eickhoff J, Traynor AM, Kirby-Slimp R, Volk LM, Werndli J, Go RS, Weiss M, Blank J, Kahl BS. Bendamustine + rituximab chemoimmunotherapy and maintenance lenalidomide in relapsed, refractory chronic lymphocytic leukaemia and small lymphocytic lymphoma: A Wisconsin Oncology Network Study. Br J Haematol. 2016 Apr;173(2):283-91. doi: 10.1111/bjh.13957. Epub 2016 Feb 23.

  PMID: 26913697 DERIVED

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin

Interventions

Bendamustine Hydrochloride; Rituximab; Lenalidomide

Condition Hierarchy (Ancestors)

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

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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles

Results Point of Contact

• Title: Julie Chang, MD
• Organization: University of Wisconsin Carbone Cancer Center

clinicaltrials@cancer.wisc.edu

800-622-9822

Study Officials

• Julie Chang, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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 9, 2012
• First Posted: December 21, 2012
• Study Start: November 12, 2013
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: June 27, 2023
• Results First Posted: June 27, 2023

Record last verified: 2023-06

Locations

US (1)