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

NCT00546377 | Completed Phase 1 Results

• 2 other identifiers: 05-077MSKCC-05077
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Leukemia; Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Overall Response

  Complete response (CR): Absence of lymphadenopathy, hepatomegaly or splenomegaly by physical examination and appropriate radiographic techniques (if abnormal pre-treatment): it is recognized that some patients with lymphoid malignancies who achieve a CR may have mild persistent abnormalities on CT Scan. Such abnormalities if stable on subsequent scanning will not be viewed as persistent disease in patients who otherwise meet the criteria for CR. Response will be assessed on an ongoing basis, but at a minimum of prior to cycle four and following completion of all therapy. Patients who are removed from study early will have response status determined at time of removal from study. 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.

  3 years

• Maximum Tolerated Dose (MTD) of Mitoxantrone

  The MTD is defined as the highest dose studied for which the incidence of DLT is less than 33%. In the phase I portion of the trial, cohorts of 3-6 pts will receive pentostatin, cyclophosphamide and rituximab along with one of three potential dose levels of mitoxantrone. The following dose escalation scheme will be followed: If none of the initial three pts in a cohort experience a dose-limiting toxicity (grade 4 infection, or grade ≥ 3 non-hematologic toxicity that persists for 7 days or more) then a new cohort of three pts will be treated at the next higher dose level. If one of the three pts in a cohort experiences DLT, then up to three additional pts will be treated at the same dose level. If two or more pts in a cohort experience DLT, then the maximum tolerated dose (MTD) will have been exceeded, and no further dose escalation will occur. The previous dose level will be considered as the MTD.

  2 years

Study Arms (1)

Mitoxantrone

EXPERIMENTAL

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

Interventions

filgrastim BIOLOGICAL

Mitoxantrone

pegfilgrastim BIOLOGICAL

Mitoxantrone

rituximab BIOLOGICAL

Mitoxantrone

sargramostim BIOLOGICAL

Mitoxantrone

cyclophosphamide DRUG

Mitoxantrone

mitoxantrone hydrochloride DRUG

Mitoxantrone

pentostatin DRUG

Mitoxantrone

fluorescence in situ hybridization GENETIC

Mitoxantrone

gene rearrangement analysis GENETIC

Mitoxantrone

polymerase chain reaction GENETIC

Mitoxantrone

protein expression analysis GENETIC

Mitoxantrone

flow cytometry OTHER

Mitoxantrone

biopsy PROCEDURE

Mitoxantrone

Eligibility Criteria

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

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

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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular

Interventions

Filgrastim; pegfilgrastim; Rituximab; sargramostim; Cyclophosphamide; Mitoxantrone; Pentostatin; In Situ Hybridization, Fluorescence; Gene Rearrangement; Polymerase Chain Reaction; Flow Cytometry; Biopsy

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; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Quinones; Polycyclic Compounds; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Cytogenetic Analysis; Genetic Techniques; Nucleic Acid Hybridization; Genetic Phenomena; Nucleic Acid Amplification Techniques; Cell Separation; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Renier Brentjens, Associate Attending
• Organization: Memorial Sloan Kettering Cancer Center

brentjer@mskcc.org

+1212-639-7053

Study Officials

• Renier Brentjens, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Andrew D. Zelenetz, MD, PhD

  Memorial Sloan Kettering Cancer Center

  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: October 17, 2007
• First Posted: October 18, 2007
• Study Start: July 1, 2005
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: May 12, 2016
• Results First Posted: May 12, 2016

Record last verified: 2016-04

Locations

US (1)