Overview

This trial is active, not recruiting.

Conditions hematopoietic/lymphoid cancer, b-cell chronic lymphocytic leukemia, contiguous stage ii small lymphocytic lymphoma, noncontiguous stage ii small lymphocytic lymphoma, stage 0 chronic lymphocytic leukemia, stage i chronic lymphocytic leukemia, stage i small lymphocytic lymphoma, stage ii chronic lymphocytic leukemia, stage iii chronic lymphocytic leukemia, stage iii small lymphocytic lymphoma, stage iv chronic lymphocytic leukemia, stage iv small lymphocytic lymphoma
Treatments pentostatin, cyclophosphamide, ofatumumab, laboratory biomarker analysis, flow cytometry, protein expression analysis
Phase phase 2
Sponsor Mayo Clinic
Start date August 2010
End date May 2014
Trial size 82 participants
Trial identifier NCT01024010, 09-003675, MC0983, NCI-2009-01437, OFT113301

Summary

RATIONALE: Monoclonal antibodies, such as ofatumumab, 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. Giving ofatumumab together with pentostatin and cyclophosphamide may be a better way to block cancer growth.

PURPOSE: This phase II trial is studying how well giving ofatumumab together with pentostatin and cyclophosphamide works in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive ofatumumab IV on days 1-2 of course 1 and on day 1 of courses 2-6. Patients also receive pentostatin IV over 30 minutes on day 1, cyclophosphamide IV over 30 minutes on day 1, and pegfilgrastim subcutaneously on day 2.
pentostatin 2'-deoxycoformycin
Given IV
cyclophosphamide CPM
Given IV
ofatumumab Arzerra
Given IV
laboratory biomarker analysis
Correlative study
flow cytometry
protein expression analysis
Correlative study
(Experimental)
Arm B: Experimental Patients receive ofatumumab IV on days 1-2 of course 1 and on day 1 of courses 2-6. Patients also receive pentostatin IV over 30 minutes on day 1, cyclophosphamide IV over 30 minutes on day 1, and pegfilgrastim subcutaneously on day 2. Patients receive ofatumumab IV on day 1 of courses 7-12. Interventions: Drug: pentostatin Drug: cyclophosphamide Biological: ofatumumab Procedure: laboratory biomarker analysis Other: flow cytometry Genetic: protein expression analysis
pentostatin 2'-deoxycoformycin
Given IV
cyclophosphamide CPM
Given IV
ofatumumab Arzerra
Given IV
laboratory biomarker analysis
Correlative study
flow cytometry
protein expression analysis
Correlative study

Primary Outcomes

Measure
Arm A: Proportion of complete responses
time frame: 7 months
Arm B: Treatment-free Survival at 18 months
time frame: 18 months

Secondary Outcomes

Measure
Overall response rate
time frame: 14 months
Complete response rate
time frame: 14 months
Depth of response after ofatumumab consolidation
time frame: 14 months
Progression-free survival
time frame: 5 years
Treatment-free survival
time frame: 5 years
Duration of response
time frame: 5 years
Differences in the distributions of risk factors (VH gene mutation, CD38, CD49d, ZAP-70 and FISH status) by clinical outcome (responders vs nonresponders)
time frame: 14 months
Adverse events
time frame: 24 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion - Diagnosis of CLL according to the NCI criteria or SLL according to the WHO criteria, including previous documentation of: - a) Biopsy-proven small lymphocytic lymphoma (SLL) or - b) Diagnosis of CLL according to NCI working group criteria as evidenced by ALL of the following: - 1) Peripheral blood lymphocyte count of > 5,000/mm^3 consisting of small to moderate size lymphocytes, with < 55% prolymphocytes - 2) Immunophenotyping consistent with CLL defined as: i) The predominant population of lymphocytes share both B-cell antigens (CD19, CD20, or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.); ii) Dim surface immunoglobulin expression; iii) Restricted surface kappa or lambda light chain expression - NOTE: Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL - 3) Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a 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 - Patients must be previously untreated and meet at least one of the following indications for chemotherapy: - a) Evidence of progressive marrow failure as manifested by the development of or worsening anemia (=< 11 g/dl) and/or thrombocytopenia (=< 100,000/mm^3) not due to autoimmune disease - b) Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly - c) One or more of the following disease-related symptoms: 1) Weight loss > 10% within the previous 6 months; 2) Extreme fatigue attributed to CLL; 3) Fevers > 100.5 degrees F for 2 weeks without evidence of infection; 4) Drenching night sweats without evidence of infection - d) Progressive lymphocytosis due to CLL with an increase of > 50% over a two month period or an anticipated doubling time of less than six months - NOTE: 1) Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments) will not be considered prior treatment - NOTE: 2) 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 - The following laboratory values obtained =< 14 days prior to registration: serum creatinine =< 1.5 x UNL; total bilirubin =< 1.5 x UNL unless due to Gilbert's disease (if total bilirubin is > 1.5 x ULN, a direct bilirubin should be performed and must be < 1.5 mg/dL for Gilbert's to be diagnosed); AST =< 3.0 x UNL and ALT =< 3.0 x UNL (unless due to hemolysis or CLL) - ECOG performance status (PS): 0, 1, or 2 - Willingness to provide blood samples as required - Able to adhere to the study visit schedule and other protocol requirements Exclusion - Any of the following comorbid conditions: New York Heart Association Class III or IV heart disease; recent myocardial infarction (< 1 month); uncontrolled infection; infection with the human immunodeficiency virus (HIV/AIDS) as further severe immunosuppression with this regimen may occur; infection with known chronic, active Hepatitis B or C or Hepatitis B carriers - Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: pregnant women; nursing women; men or women of childbearing potential who are unwilling to employ adequate contraception - Other active primary malignancy requiring treatment or limiting survival to =< 2 years - Any radiation therapy =< 4 weeks prior to registration - Any major surgery =< 4 weeks prior to registration - Current use of corticosteroids (EXCEPTION: Low doses of steroids [< 10 mg of prednisone or equivalent dose of other steroid] used for treatment of non-hematologic medical conditions; NOTE: Previous use of corticosteroids is allowed) - Active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation

Additional Information

Official title Phase II Trial of Pentostatin, Cyclophosphamide, and Ofatumumab For Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL)
Principal investigator Jose Leis, M.D.
Description PRIMARY OBJECTIVES: I. Arm A: To assess the rate of complete response using pentostatin, cyclophosphamide, and ofatumumab in patients with previously untreated CLL or SLL requiring therapy. II. Arm B: To assess the treatment-free survival rate at 18 months using pentostatin,cyclophosphamide, and ofatumumab induction therapy followed by ofatumumab consolidation in patients with previously untreated CLL or SSLL requiring therapy. SECONDARY OBJECTIVES: I. Arm A and Arm B: To assess the rate of overall response in patients with previously untreated CLL or SLL requiring therapy and to determine the proportion of patients who achieve a minimal residual disease (MRD) negative state as assessed by flow cytometry in each arm independently. II. Arm A and Arm B: To monitor and assess toxicity in patients with previously untreated CLL or SLL in each arm independently. III. Arm A and Arm B: To determine the progression-free survival, treatment-free survival, and duration of response in each arm independently. IV. Arm A and Arm B: To determine if molecular prognostic parameters (ZAP-70, CD38, cytogenetic abnormalities identified by FISH, IgVH mutation status, etc) relate to response to therapy in each arm independently. V: Arm B: To assess the rate of complete response using pentostatin, cyclophosphamide, and ofatumumab induction followed by ofatumumab consolidation in patients with previously untreated CLL or SLL requiring therapy. VI: Arm B: To evaluate whether consolidation therapy with ofatumumab after PCO induction improves the depth of response. OUTLINE: Patients receive ofatumumab IV on days 1-2 of course 1 and on day 1 of courses 2-6. Patients also receive pentostatin IV over 30 minutes on day 1, cyclophosphamide IV over 30 minutes on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients on Arm B receive additional courses with single agent ofatumumab IV on day 1 for 6 courses (courses 7-12). Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by Mayo Clinic.