Ixabepilone in Treating Patients With Relapsed or Refractory Lymphoproliferative Disorders

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Lymphoma; Leukemia

Treatments: Drug: ixabepilone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00052572

MSKCC-02046

CDR0000258542

NCI-5342

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of ixabepilone in treating patients who have relapsed or refractory lymphoproliferative disorders.

Full description

OBJECTIVES:

Primary

• Determine the frequency and duration of complete and partial response rates for patients with relapsed or refractory indolent lymphoproliferative disorders treated with ixabepilone.

Secondary

• Determine the time to progression and overall survival of patients treated with this drug.
• Determine the toxicity of this drug in these patients.

OUTLINE: This is an open-label study.

Patients receive ixabepilone IV over 1 hour weekly for 3 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study within 1-1.5 years.

Enrollment: 35 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed relapsed/recurrent or refractory indolent lymphoproliferative disorder of 1 of the following types:

  • Chronic lymphocytic leukemia

    • Absolute lymphocytosis greater than 5,000/mm^3
    • B-cell phenotype (CD 19, 20, or 23 positive) with more than 30% bone marrow lymphocytes

  • B-cell small lymphocytic lymphoma

  • Marginal zone B-cell lymphoma

  • Grade I-III follicle center cell lymphoma

  • Waldenstrom's macroglobulinemia

  • Mantle cell lymphoma

• At least 1 unidimensionally measurable lesion for patients with non-Hodgkin's lymphoma

  • At least 2 cm by conventional techniques

• No active brain metastases

  • Treated CNS disease allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3 (500/mm^3 if there is lymphomatous involvement of the bone marrow)
• Platelet count ≥ 50,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 2.5 times ULN (4 times ULN if there is liver involvement)

Renal

• Creatinine ≤ 2 times ULN OR
• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No history of orthostatic hypotension

• No myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 3 months

• No New York Heart Association class III or IV congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• No uncontrolled hypertension requiring manipulation of antihypertensive medications

• No evidence of any of the following by echocardiogram:

  • Acute ischemia

  • Significant conduction abnormality

    • Bifascicular block
    • 2^nd- or 3^rd-degree atrioventricular block

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No other immunodeficiency
• No known severe hypersensitivity reaction to agents containing Cremophor EL
• No ongoing or active infection
• Febrile episodes up to 38.5° Celsius allowed in the absence of infection
• No other concurrent uncontrolled illness that would preclude study participation
• No psychiatric illness or social situation that would preclude study compliance
• No preexisting grade II or greater sensory neuropathy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 3 months since prior monoclonal antibodies (unless there is clearly documented evidence of disease progression after therapy)
• At least 3 months since prior radioimmunotherapy
• No prior allogeneic bone marrow transplantation

Chemotherapy

• At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin, nitrosoureas, or carmustine) and recovered

• No more than 4 prior chemotherapy regimens (including high-dose chemotherapy [HDC] for patients with relapsed disease > 100 days after completion of HDC)

  • Cytoreduction plus HDC is considered 1 chemotherapy regimen

• No other concurrent chemotherapy

Endocrine therapy

• At least 7 days since prior steroids

Radiotherapy

• More than 3 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior major surgery

Other

• Use of antibiotics for marginal zone lymphoma does not count as a prior therapy
• No other concurrent investigational agents
• No other concurrent anticancer therapy