Rituximab, Bendamustine Hydrochloride, and Lenalidomide in Treating Patients With Refractory or Relapsed Indolent Non-Hodgkin Lymphoma

NCT01429025 | Completed Phase 1 DMC

• 3 other identifiers: NCCTG-N1088CDR0000710726NCI-2011-03535
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 17

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. Lenalidomide may stop the growth of non-Hodgkin lymphoma by blocking blood flow to the cancer. Giving lenalidomide together with rituximab and bendamustine hydrochloride may kill more cancer cells. PURPOSE: This phase I trial studies the side effects and the best dose of giving lenalidomide together with rituximab and bendamustine hydrochloride in treating patients with refractory or relapsed indolent non-Hodgkin lymphoma.

Conditions

Refractory/Relapsed Indolent Non-Hodgkin Lymphoma

Keywords

recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; Waldenström macroglobulinemia; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated dose of lenalidomide in combination with bendamustine hydrochloride and rituximab

  Up to 28 days

Secondary Outcomes (4)

• Toxicity profile

  Up to 5 years

• Progression-free survival

  Time from registration to the earliest date of documented disease progression or death due to any cause, assessed up to 5 years

• Overall response rate

  Up to 5 years

• Complete response rate

  Up to 5 years

Study Arms (1)

rituximab, bendamustine and lenalidomide

EXPERIMENTAL

Patients receive rituximab IV on day 1, bendamustine IV on days 1-2, and lenalidomide PO on days 1-10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: rituximab; Drug: bendamustine; Drug: lenalidomide

Interventions

rituximab BIOLOGICAL

IV

rituximab, bendamustine and lenalidomide

bendamustine DRUG

IV

rituximab, bendamustine and lenalidomide

lenalidomide DRUG

PO

rituximab, bendamustine and lenalidomide

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Histologically confirmed relapsed (recurrent after previous therapy (-ies)) or refractory (no response to previous therapy (-ies)), CD20 + indolent/low-grade B-cell non-Hodgkin lymphoma (NHL) expressing CD20 antigen. Criteria for diagnosis can be found in reference J Clin Oncol 17(4): 1244-53, 1999. The biopsy confirming relapse can be up to 12 weeks prior to registration as long as there is no intervening therapy. If patients have been on active treatment within the the last 12 weeks, the tumor biopsy must be repeated before study enrollment to evaluate for transformation.
• Small lymphocytic lymphoma (SLL) excluding chronic lymphocytic leukemia (CLL) (patients with peripheral blood lymphocyte count \> 5,000)
• Follicular lymphoma, grades 1, 2 (grade 3 excluded)
• Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphatic tissue (MALT) type
• Lymphoplasmacytic lymphoma including Waldenstrom macroglobulinemia
• Measurable disease (at least 1 lesion of ≥ 1.5 cm in diameter) as detected by computed tomography (CT) or the CT images of the positron emission tomography (PET)/CT. Patients with Waldenstrom macroglobulinemia are not required to have measurable disease by CT or PET/CT if monoclonal protein is detectable by serum protein electrophoresis and/or IgM level is at least 2 times upper limit of normal
• ECOG Performance Status (PS) 0, 1 or 2
• Required laboratory values obtained ≤ 21 days prior to registration:
• ANC ≥ 1,500/mL
• Platelet count ≥ 100,000/mL
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) OR, if total bilirubin is \> 1.5 x ULN, the direct bilirubin must be normal
• SGOT (AST) ≤ 5 x ULN
• Creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula as outlined in the protocol
• All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. The Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods are provided in the protocol for more information.

You may not qualify if:

• This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant women
• Nursing women (lactating females are eligible provided that they agree not to breast feed while taking lenalidomide)
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Active CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Prior AIDS-defining conditions. Note: HIV positive patients without history of AIDS- defining conditions are eligible
• If HIV positive, CD4 cells \< 400/mm\^3
• Current treatment with zidovudine (AZT) (which may cause overlapping adverse events, primarily myelosuppression). Patients receiving anti-retroviral therapy other than AZT are eligible
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator
• Celgene Corporation: collaborator

Study Sites (17)

Medical Oncology and Hematology Associates-West Des Moines

Clive, Iowa, 50325, United States

Location

Mercy Cancer Center-West Lakes

Clive, Iowa, 50325, United States

Location

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Iowa Oncology Research Association CCOP

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates-Des Moines

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates

Des Moines, Iowa, 50314, United States

Location

Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

Iowa Lutheran Hospital

Des Moines, Iowa, 50316, United States

Location

Siouxland Hematology-Oncology

Sioux City, Iowa, 51101-1733, United States

Location

Mercy Medical Center-Sioux City

Sioux City, Iowa, 51104, United States

Location

St. Luke's Regional Medical Center

Sioux City, Iowa, 51104, United States

Location

Methodist West Hospital

West Des Moines, Iowa, 50266-7700, United States

Location

Mercy Medical Center-West Lakes

West Des Moines, Iowa, 50266, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Mid Dakota Clinic

Bismarck, North Dakota, 58501, United States

Location

Saint Alexius Medical Center

Bismarck, North Dakota, 58501, United States

Location

Sanford Bismarck Medical Center

Bismarck, North Dakota, 58501, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia

Interventions

Rituximab; Bendamustine Hydrochloride; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Grzegorz S. Nowakowski, MD

  Mayo Clinic

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2011
• First Posted: September 5, 2011
• Study Start: May 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: July 1, 2019
• Last Updated: October 8, 2019

Record last verified: 2019-10

Locations

US (17)