Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00546377
First received: October 17, 2007
Last updated: December 23, 2013
Last verified: December 2013
  Purpose

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 and mitoxantrone, 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 combination chemotherapy and rituximab may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of mitoxantrone when given together with pentostatin, cyclophosphamide, and rituximab and to see how well it works in treating patients with chronic lymphocytic leukemia or other low-grade B-cell cancer.


Condition Intervention Phase
Leukemia
Lymphoma
Biological: filgrastim
Biological: pegfilgrastim
Biological: rituximab
Biological: sargramostim
Drug: cyclophosphamide
Drug: mitoxantrone hydrochloride
Drug: pentostatin
Genetic: fluorescence in situ hybridization
Genetic: gene rearrangement analysis
Genetic: polymerase chain reaction
Genetic: protein expression analysis
Other: flow cytometry
Procedure: biopsy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I-II Study of Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Previously Treated Patients With Chronic Lymphocytic Leukemia and Other Low Grade B-Cell Neoplasms

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Overall response including complete response, clinical complete response, nodular response, and partial response [ Time Frame: Prior to cycle 4 and after completion of all therapy ] [ Designated as safety issue: No ]
  • Maximum tolerated dose [ Time Frame: After each cycle ] [ Designated as safety issue: Yes ]
  • Toxicity [ Time Frame: After each cycle ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 63
Study Start Date: July 2005
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mitoxantrone Biological: filgrastim Biological: pegfilgrastim Biological: rituximab Biological: sargramostim Drug: cyclophosphamide Drug: mitoxantrone hydrochloride Drug: pentostatin Genetic: fluorescence in situ hybridization Genetic: gene rearrangement analysis Genetic: polymerase chain reaction Genetic: protein expression analysis Other: flow cytometry Procedure: biopsy

Detailed Description:

OBJECTIVES:

  • To determine the dose of mitoxantrone hydrochloride that can be safely administered with pentostatin, cyclophosphamide, and rituximab in patients with previously treated chronic lymphocytic leukemia or other low-grade B-cell malignancies.
  • To characterize the toxicity of this regimen in these patients.
  • To determine the response rate in patients treated with this regimen.

OUTLINE: This is a phase I, dose-escalation study of mitoxantrone hydrochloride followed by a phase II study.

  • Phase I: Patients receive pentostatin IV, cyclophosphamide IV, and mitoxantrone hydrochloride IV on day 1. Patients also receive rituximab IV on day 1 beginning in course 2. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
  • Phase II: Patients receive pentostatin, cyclophosphamide, rituximab, and mitoxantrone hydrochloride (at the maximum tolerated dose determined in phase I) as in phase I.

All patients receive either pegfilgrastim subcutaneously (SC) on days 1-4 following each course or filgrastim or sargramostim SC beginning 2 days after each course until blood counts recover.

Patients undergo blood collection and bone marrow biopsy periodically for assessment of therapy response by biomarker and laboratory studies. Samples are analyzed for molecular genetics for IgH arrangement by PCR and for response by immunoelectrophoresis. Some samples are analyzed for response by flow cytometry or fluorescence in situ hybridization (FISH).

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

PROJECTED ACCRUAL: A total of 63 patients (18 patients for phase I and 45 patients for phase II) will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following diseases confirmed by a Memorial Sloan-Kettering Cancer Center (MSKCC) pathologist:

    • Chronic lymphocytic leukemia meeting the following risk criteria as defined by the three-stage Rai system:

      • Intermediate-risk disease meeting the following criteria for active disease as defined by the NCI Working Group:

        • Weight loss
        • Fatigue
        • Fevers
        • Evidence of progressive marrow failure
        • Splenomegaly
        • Progressive lymphadenopathy
        • Progressive lymphocytosis with a rapid doubling time, defined as doubling time less than 6 months and absolute lymphocyte count > 30,000/μL
      • High-risk disease
    • Other low grade B-cell neoplasms, including any of the following:

      • Small lymphocytic lymphoma
      • Follicular lymphoma
      • Waldenstrom macroglobulinemia
      • Marginal zone lymphomas
      • Mantle cell lymphomas
      • Transformed lymphoma
  • Previously treated disease

    • Must have received prior cytotoxic therapy
  • Malignant lymphocytes must demonstrate B-cells via immunophenotypic or immunohistochemical analysis NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • Life expectancy > 8 weeks
  • 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, 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
  • Normal cardiac ejection fraction ≥ 50% (increased ejection fraction [at least 5% over rest]) required for study eligibility

    • Borderline (40-50%) ejection fraction must undergo a stress echocardiogram or MUGA scan
  • Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are eligible for treatment
  • Must have undergone consultation with the primary investigator or his/her designee prior to study entry
  • No significant active infections
  • No ongoing hepatitis B infection, specifically hepatitis B antigen or surface antigen positivity

    • Hepatitis B antibody-positive patients are eligible

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • The following concurrent medications are allowed:

    • Intravenous immunoglobulin (IVIG)
    • Erythropoietin, darbepoetin, filgrastim, or sargramostim
    • Cyclosporine (only for patients with cellular immune cytopenias [i.e., pure red cell aplasia]), with required consultation of the principle investigator or designee
  • Concurrent prednisone allowed provided it is used as brief courses (≤ 7 days) for inflammatory conditions unrelated to CLL
  • No concurrent chemotherapy or radiotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00546377

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Renier Brentjens, MD, PhD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Andrew D. Zelenetz, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00546377     History of Changes
Other Study ID Numbers: 05-077, MSKCC-05077
Study First Received: October 17, 2007
Last Updated: December 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
B-cell chronic lymphocytic leukemia
Waldenstrom macroglobulinemia
recurrent mantle cell lymphoma
recurrent small lymphocytic lymphoma
refractory chronic lymphocytic leukemia
recurrent marginal zone lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Mitoxantrone
Pentostatin
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on April 14, 2014