Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia

• ClinicalTrials.gov Identifier: NCT00541034
• Recruitment Status: Completed
• First Posted: October 8, 2007
• Results First Posted: February 27, 2017
• Last Update Posted: August 11, 2017
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI); Astex Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: October 5, 2007
• First Posted Date: October 8, 2007
• Results First Submitted Date: January 9, 2017
• Results First Posted Date: February 27, 2017
• Last Update Posted Date: August 11, 2017
• Study Start Date: May 2005
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 13, 2017)

Overall Objective Response [ Time Frame: 2 years ]

The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment, will be repeated to document the degree of maximal response.

Original Primary Outcome Measures (submitted: October 5, 2007)

• Complete response
• Toxicity

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia
• Official Title: Phase II Study of Pentostatin With Cyclophosphamide and Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia

Brief Summary

RATIONALE: Pentostatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. Giving pentostatin together with cyclophosphamide and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects and how well giving pentostatin together with cyclophosphamide and rituximab works in treating patients with previously untreated chronic lymphocytic leukemia.

Detailed Description

OBJECTIVES:

• To determine the frequency of response in patients with previously untreated, intermediate- or high-risk B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab.
• To characterize the toxicity of this regimen in these patients.

OUTLINE: Patients receive cyclophosphamide IV followed by pentostatin IV on day 1 in course 1. Beginning in course 2 and in all subsequent courses, patients receive cyclophosphamide IV on day 1, pentostatin IV on day 1, and rituximab IV on day 1 or on days 1 and 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at least every 3 months for 1 year.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Leukemia
• Lymphoma

Intervention

• Biological: rituximab
• Drug: cyclophosphamide
• Drug: pentostatin

Study Arms

Experimental: cyclophosphamide, pentostatin & rituximab

Patients receive cyclophosphamide IV followed by pentostatin IV on day 1 in course 1. Beginning in course 2 and in all subsequent courses, patients receive cyclophosphamide IV on day 1, pentostatin IV on day 1, and rituximab IV on day 1 or on days 1 and 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Interventions:

• Biological: rituximab
• Drug: cyclophosphamide
• Drug: pentostatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 12, 2013): 49
• Original Enrollment (submitted: October 5, 2007): 46
• Actual Study Completion Date: January 2016
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL), as evidenced by an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter OR bone marrow lymphocytosis ≥ 30% of all nucleated cells

  • Previously untreated disease

• Meets 1 of the following risk criteria as defined by the three-stage Rai system

  • Intermediate-risk disease

    • Must meet the criteria for active disease as defined by the NCI Working Group guidelines including the following:

      • Weight loss
      • Fatigue
      • Fevers
      • Evidence of progressive marrow failure
      • Splenomegaly
      • Progressive lymphadenopathy
      • Progressive lymphocytosis with a rapid doubling time
  • High-risk disease
• Malignant lymphocytes must demonstrate B-cells via immunophenotypic or immunohistochemical analysis
• Patients with small lymphocytic lymphoma (CLL type) are eligible

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status 60-100%
• Total bilirubin ≤ 2.0 mg/dL (patients with Gilbert disease or autoimmune hemolytic anemia should have an evaluation for other causes of hyperbilirubinemia, but if none are found they may be enrolled regardless of serum bilirubin)
• Total creatinine ≤ 2.0 mg/dL OR creatinine clearance > 50 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are eligible for treatment on this protocol regardless of disease stage

Exclusion criteria:

• Significant active infections

• Ongoing hepatitis B infection, specifically hepatitis B antigen or surface antigen positivity

  • Patients who are hepatitis B antibody positive are eligible for this protocol

PRIOR CONCURRENT THERAPY:

• Concurrent prednisone allowed provided it is used as brief courses (≤ 7 days) for inflammatory conditions unrelated to CLL
• No prior cytotoxic therapy or rituximab for this cancer
• No concurrent radiotherapy or other chemotherapy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00541034
• Other Study ID Numbers: 05-051; P30CA008748 ( U.S. NIH Grant/Contract ); MSKCC-05051
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Memorial Sloan Kettering Cancer Center
• Original Responsible Party: Not Provided
• Current Study Sponsor: Memorial Sloan Kettering Cancer Center
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Institute (NCI)
• Astex Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Nicole Lamanna, MD; Memorial Sloan Kettering Cancer Center
• Principal Investigator: Renier Brentjens, MD, PhD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: July 2017