Phase 2
N=50
Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer
Leukemia · Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT00546377 ↗Enrolled (actual)
50
Serious AEs
44.2%
Results posted
May 2016
Primary outcome: Primary: Overall Response — 11; 23; 4; 5 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- filgrastim (Biological); pegfilgrastim (Biological); rituximab (Biological); sargramostim (Biological); cyclophosphamide (Drug); mitoxantrone hydrochloride (Drug); pentostatin (Drug); fluorescence in situ hybridization (Genetic); gene rearrangement analysis (Genetic); polymerase chain reaction (Genetic); protein expression analysis (Genetic); flow cytometry (Other); biopsy (Procedure)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Primary completion
- May 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Response |
11; 23; 4; 5 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of Mitoxantrone |
10 | — |
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.
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT00546377). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.