Lenalidomide, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large Cell or Follicular B-Cell Lymphoma

NCT00670358 | Completed Phase 1 Results DMC

• 5 other identifiers: MC078ERV-NHL-PI-032507-007992NCI-2009-01196P50CA097274
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with rituximab and combination chemotherapy may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of lenalidomide when given together with rituximab and combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II, stage III, or stage IV diffuse large cell or follicular B-cell lymphoma.

Conditions

Lymphoma

Keywords

contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; contiguous stage II grade 3 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 3 follicular lymphoma

Outcome Measures

Primary Outcomes (3)

• Toxicity as Assessed by NCI CTCAE v3.0 (Phase I)

  5 years

• Event-free > Survival at 12 Months (Phase 2, DLBCL/Mixed Dose Level 3)

  Other Phase II Cohorts were not evaluable for event-free survival analysis.

  1 year

• Progression-free > Survival at 24 Months (Phase 2, Transformed/Composite)

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Other Phase II Cohorts were not evaluable for progression-free survival analysis.

  2 years

Secondary Outcomes (8)

• Overall Response Rate

  When all patients either have a CR or have completed observation.

• Overall Complete Response Rate

  When all patients either have a CR or have completed observation.

• Event-free Survival

  5 years

• Overall Survival

  5 years

• Progression-free Survival

  5 years

Interventions

pegfilgrastim BIOLOGICAL

rituximab BIOLOGICAL

cyclophosphamide DRUG

doxorubicin hydrochloride DRUG

lenalidomide DRUG

prednisone DRUG

vincristine sulfate DRUG

polymorphism analysis GENETIC

laboratory biomarker analysis OTHER

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed diffuse large cell or grade 3A/B follicular lymphoma * Newly diagnosed disease * Stage II, III, or IV disease * Measurable disease, defined as ≥ 1 lesion ≥ 1.5 cm in one diameter, as detected by CT scan or PET-CT scan (PET/CT fusion) * CD20-positive disease * No post-transplant lymphoproliferative disorder (PTLD) * No CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal * Alkaline phosphatase ≤ 3 times ULN (5 times ULN if direct liver involvement by lymphoma) * AST ≤ 3 times ULN (5 times ULN if direct liver involvement by lymphoma) * Creatinine ≤ 2 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile female patients must use effective double-method contraception for ≥ 28 days before, during, and for ≥ 28 days after completion of study therapy * Fertile male patients must use effective contraception during and for ≥ 28 days after completion of study therapy, even if they have had a successful vasectomy * No blood, sperm, or semen donation during and for ≥ 28 days after completion of study therapy * Willing to return to enrolling institution for follow-up * Willing to provide blood samples for translational research purposes * No comorbid systemic illness or other severe concurrent disease that, in the judgment of the investigator, would preclude study entry or significantly interfere with the proper assessment of safety and toxicity of the prescribed study regimen * No known HIV positivity * Not immunocompromised * No concurrent uncontrolled illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situation that would preclude compliance with study requirements * No other active malignancy, except localized nonmelanotic skin cancer or any cancer that, in the judgment of the investigator, has been treated with curative intent and will not interfere with the study treatment plan and response assessment * No myocardial infarction within the past 6 months * No congestive heart failure requiring ongoing maintenance therapy for life-threatening ventricular arrhythmias * Ejection fraction ≥ 45% by MUGA or ECHO * No history of life threatening or recurrent thrombosis/embolism (unless on anticoagulation therapy during study treatment) PRIOR CONCURRENT THERAPY: * No prior radiotherapy to ≥ 25% of the bone marrow * No concurrent erythroid-stimulating agents (e.g., Procrit, Aranesp) * No other concurrent treatment for lymphoma * No concurrent radiotherapy, chemotherapy, or immunotherapy for another active malignancy * Able to receive concurrent prophylactic anticoagulation therapy (e.g., low-dose aspirin \[81 mg\] daily or an alternative prophylaxis \[e.g., warfarin or low molecular weight heparin\])

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Gascoyne RD, Habermann TM, Witzig TE. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma: a phase II study. J Clin Oncol. 2015 Jan 20;33(3):251-7. doi: 10.1200/JCO.2014.55.5714. Epub 2014 Aug 18.

  PMID: 25135992 DERIVED

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Interventions

pegfilgrastim; Rituximab; Cyclophosphamide; Doxorubicin; Lenalidomide; Prednisone; Vincristine; Amplified Fragment Length Polymorphism Analysis

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; DNA Fingerprinting; Genetic Techniques; Investigative Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques

Results Point of Contact

• Title: Dr. Grzegorz Nowakowski
• Organization: Mayo Clinic

Nowakowski.Grzegorz@mayo.edu

507-284-5096

Study Officials

• Grzegorz S. Nowakowski, M.D.

  Mayo Clinic

  STUDY CHAIR

• Allison C. Rosenthal, D.O.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Candido E. Rivera, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: April 30, 2008
• First Posted: May 1, 2008
• Study Start: August 25, 2008
• Primary Completion: May 7, 2021
• Study Completion: October 4, 2024
• Last Updated: January 10, 2025
• Results First Posted: November 17, 2022

Record last verified: 2024-12

Locations

US (3)