Rituximab, Pentostatin, Cyclophosphamide, and Lenalidomide in Treating Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT00602836 | Completed Phase 2 Results DMC

• 6 other identifiers: CDR0000582676P30CA015083MC078407-002156RV-CLL-PI-146NCI-2009-01281
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: 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 pentostatin and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving rituximab together with combination chemotherapy and lenalidomide may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with pentostatin, cyclophosphamide, and lenalidomide works in treating patients with previously untreated B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

Conditions

Leukemia; Lymphoma

Keywords

B-cell chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; contiguous stage II small lymphocytic lymphoma; noncontiguous stage II small lymphocytic lymphoma; stage I small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Complete Response (CR)

  A complete response, as defined by the National Cancer Institute Working Group (NCIWG), requires all of the following for a period of at least 2 months: \- CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy

  12 months

Secondary Outcomes (5)

• Number of Participants Who Convert From a Nodular Partial Response (nPR), Partial Response (PR), or Stable Disease (SD) After Pentostatin, Cyclophosphamide, and Rituximab (PCR) to a Complete Response (CR) After 6 Courses of Consolidation With Lenalidomide

  12 months

• Number of Participants Who Convert From a CR With Minimal Residual Disease (MRD) Positive Status After PCR to a CR With MRD-negative Status After 6 Courses of Consolidation With Lenalidomide

  12 months

• Number of Participants With a Response (CR, nPR, PR)

  During treatment (up to 5 years)

• Overall Survival (OS)

  time from registration to death (up to 5 years)

• Treatment Free Survival (TFS)

  time from registration to progression (up to 5 years)

Study Arms (1)

PCR-Lenalidomide

EXPERIMENTAL

Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide

Biological: Rituximab; Drug: Cyclophosphamide; Drug: Lenalidomide; Drug: Pentostatin

Interventions

Rituximab BIOLOGICAL

Cycle 1: 100 mg by IV on day 1, 375 mg/m\^2 by IV on day 2 Cycle 2-6: 375 mg/m\^2 by IV on day 1 (every 21 days)

PCR-Lenalidomide

Cyclophosphamide DRUG

600 mg/m\^2 by IV on day 1 of cycles 1-6 (every 21 days)

PCR-Lenalidomide

Lenalidomide DRUG

Cycle 7: 5 mg orally daily on days 1-28 Cycle 8: 10 mg orally daily on days 1-28 as tolerability permits Cycle 9 and beyond: 10 mg orally daily on days 1-28

PCR-Lenalidomide

Pentostatin DRUG

2 mg/m\^2 by IV on day 1 of cycles 1-6 (every 21 days)

PCR-Lenalidomide

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), meeting the following criteria: * Biopsy-proven SLL according to WHO criteria * CLL diagnosis\* according to NCI working group criteria as evidenced by all of the following: * Peripheral blood lymphocyte count of \> 5,000/mm³ * Small to moderate peripheral blood lymphocyte with \< 55% prolymphocytes * Immunophenotyping consistent with CLL defined as: * B-cell markers with CD5 antigen in the absence of other pan-T-cell markers (e.g., CD3, CD2) * CD19, CD20, or CD23 * Dim surface immunoglobulin expression * Exclusively kappa or lambda light chains * Diagnosis of mantle cell lymphoma must be excluded by negative FISH analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy NOTE: \*Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL * Previously untreated disease and meets ≥ 1 of the following criteria\*: * At least 1 or more of the following disease-related symptoms: * Weight loss \> 10% within the previous 6 months * Extreme fatigue attributed to CLL * Fevers \> 100.5º F for 2 weeks without evidence of infection * Night sweats without evidence of infection * Evidence of progressive marrow failure as manifested by the development of or worsening anemia (i.e., hemoglobin ≤ 11 g/dL) and/or thrombocytopenia (i.e., platelet count ≤ 100,000/mm³) not due to autoimmune disease * Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly * Progressive lymphocytosis due to CLL with an increase of \> 50% over a 2-month period or an anticipated doubling time \< 6 months NOTE: \*Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient for protocol therapy PATIENT CHARACTERISTICS: * ECOG performance status 0-3 * Serum creatinine ≤ 1.5 times upper limit of normal (ULN) * Total bilirubin ≤ 3.0 times ULN (unless due to Gilbert disease) * Direct bilirubin \< 1.5 mg/dL for Gilbert disease to be diagnosed if total bilirubin \> 3.0 times ULN * AST and ALT ≤ 3.0 times ULN (unless due to hemolysis or CLL) * Willing to provide blood samples * Able to take acetylsalicylic acid (ASA) (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use low molecular weight heparin) * Not pregnant or nursing * Negative pregnancy test * Female patients must use effective double-method contraception beginning 1 month prior to, during, and for 4 weeks after completion of study treatment * Male patients must use effective contraception during and for 4 weeks after completion of study treatment * No comorbid conditions, including any of the following: * New York Heart Association class III or IV heart disease * Recent myocardial infarction (\< 1 month) * Uncontrolled infection * Infection with HIV/AIDS * No other active primary malignancy requiring treatment or that limits survival to ≤ 2 years * No history of deep venous thrombosis or pulmonary embolism ≤ 12 months prior to study registration * No active hemolytic anemia requiring immunosuppressive or other pharmacologic therapy PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior chemotherapy or monoclonal antibody-based therapy for treatment of CLL * Nutraceutical treatments with no established benefit in CLL (e.g., epigallocatechin gallate or other herbal treatments) are not considered prior therapy * More than 4 weeks since prior radiotherapy * At least 4 weeks since prior major surgery * No concurrent corticosteroids * Concurrent low doses of steroids (e.g., \< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical conditions allowed * Prior use of corticosteroids allowed * No prior thalidomide or lenalidomide * No concurrent therapeutic doses of coumadin-derivative anticoagulants (e.g., warfarin) * Doses of ≤ 2 mg daily allowed for thrombosis prophylaxis * Prophylactic doses of low molecular weight heparin allowed

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 Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Rituximab; Cyclophosphamide; Lenalidomide; Pentostatin

Condition Hierarchy (Ancestors)

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

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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr. Tait Shanafelt
• Organization: Mayo Clinic

shanafelt.tait@mayo.edu

Study Officials

• Tait D. Shanafelt, MD

  Mayo Clinic

  STUDY CHAIR

• Han Win Tun, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Jose F. Leis, MD, PhD

  Mayo Clinic

  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: January 12, 2008
• First Posted: January 28, 2008
• Study Start: February 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: September 12, 2017
• Last Updated: January 27, 2020
• Results First Posted: April 11, 2012

Record last verified: 2017-09

Locations

US (3)