Combination Chemotherapy in Treating Patients With Recurrent or Refractory Leukemia or Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining cytarabine and mitoxantrone in treating patients who have recurrent or refractory leukemia or lymphoma.

Detailed Description
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OBJECTIVES: Determine non-hematologic toxic effects of high-dose cytarabine and high-dose mitoxantrone in patients with recurrent or refractory leukemia or lymphoma. Determine the in vitro T/NK lymphocyte proliferative responses to patient's leukemia/lymphoma cells before and after treatment with this regimen. OUTLINE: Patients receive high-dose cytarabine IV over 1 hour on days 1-5 and high-dose mitoxantrone IV over 15-30 minutes on day 5. Patients also receive sargramostim (GM-CSF) subcutaneously beginning on day 14 and continuing until blood counts recover. Patients who achieve at least stable disease or a response may receive a second course beginning at least 14 days after the first course is completed. Patients are followed for 3 months. PROJECTED ACCRUAL: A total of 20-30 patients will be accrued for this study within approximately 2-3 years.

Official Title
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A Pilot Study Of Cytarabine And High-Dose Mitoxantrone For Relapsed Or Refractory Hematologic Malignancies

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: sargramostim
* Drug: cytarabine
* Drug: mitoxantrone hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: One of the following must be present: Histologically confirmed acute myeloid leukemia or acute lymphoblastic leukemia More than 5% blasts in the bone marrow or peripheral blood unrelated to recovery of normal hematopoiesis from prior chemotherapy Failed at least 1 attempt at induction chemotherapy Diagnosis of non-Hodgkin's lymphoma or Hodgkin's lymphoma Refractory or relapsed after at least 1 regimen of standard chemotherapy Diagnosis of chronic myelogenous leukemia in accelerated phase or blast crisis Received at least 1 myelotoxic chemotherapy regimen Active CNS involvement allowed PATIENT CHARACTERISTICS: Age 55 and under Performance status ECOG 0-2 Life expectancy At least 5 weeks Hematopoietic Lymphoma patients: WBC at least 2,000/mm^3* Platelet count at least 20,000/mm^3* NOTE: *Unless due to bone marrow involvement or disease process Hepatic Bilirubin no greater than 3 times normal* AST/ALT no greater than 3 times normal* Alkaline phosphatase no greater than 3 times normal* No severe liver failure NOTE: *Unless related to leukemia Renal Creatinine clearance greater than 50 mL/min No severe renal failure Cardiovascular LVEF at least 45% by MUGA Pulmonary DLCO at least 60% of predicted Other HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No psychiatric illness that would preclude informed consent No medical illness or other condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics At least 24 hours since prior hydroxyurea At least 1 week since other prior chemotherapy Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other Recovered from prior therapy

Ages Eligible for Study
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Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: sargramostim|Sargramostim (GM-CSF) subcutaneously beginning on day 14 and continuing until blood counts recover.|
|Drug: cytarabine|high-dose cytarabine IV over 1 hour on days 1-5|
|Drug: mitoxantrone hydrochloride|high-dose mitoxantrone IV over 15-30 minutes on day 5.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival at day 14 (myeloid engraftment) |  | day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious infections by clinical, radiologic, microbiology assessment during and after treatment |  | followed for 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent marginal zone lymphoma, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent/refractory childhood Hodgkin lymphoma, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, childhood chronic myelogenous leukemia, atypical chronic myeloid leukemia, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12)