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A PHASE II STUDY OF MITOXANTRONE AND HIGH-DOSE ARA-C FOLLOWED BY INTENSIVE CONSOLIDATION WITH CYCLOPHOSPHAMIDE AND ETOPOSIDE FOR MYELOID BLAST CRISIS OF CHRONIC MYELOGENOUS LEUKEMIA (CML)


Phase 2
16 Years
N/A
Not Enrolling
Both
Leukemia

Thank you

Trial Information

A PHASE II STUDY OF MITOXANTRONE AND HIGH-DOSE ARA-C FOLLOWED BY INTENSIVE CONSOLIDATION WITH CYCLOPHOSPHAMIDE AND ETOPOSIDE FOR MYELOID BLAST CRISIS OF CHRONIC MYELOGENOUS LEUKEMIA (CML)


OBJECTIVES:

- Determine the effectiveness of induction with high-dose mitoxantrone and cytarabine in
patients with chronic myelogenous leukemia (CML) in blast crisis.

- Determine the toxicity and activity of consolidation with high-dose cyclophosphamide
and etoposide in these patients.

- Determine the toxicity and activity of maintenance with interferon alfa in these
patients.

- Determine the efficacy and tolerability of this regimen in these patients.

- Assess minimal residual disease by cytogenetics, DNA gene rearrangement (Southern
blotting), and polymerase chain reaction (PCR) in patients treated with this regimen,
and use semiquantitative PCR to evaluate the antileukemic activity of subsequent phases
of treatment in patients achieving complete remission.

OUTLINE: Patients are stratified by prior therapy for blast crisis (yes vs no).

- Induction: Patients receive high-dose cytarabine IV over 3 hours on days 1-5 and
mitoxantrone IV on day 3. Sargramostim (GM-CSF) is administered subcutaneously (SC) (or
IV over 4 hours) daily beginning on day 7 and continuing until blood counts recover.
After completion of induction, patients with a suitable HLA-identical bone marrow donor
undergo allogeneic bone marrow transplantation according to an appropriate IRB-approved
protocol. Patients without a donor proceed to consolidation approximately 4 weeks after
hospital discharge following induction.

- Consolidation: Patients receive high-dose cyclophosphamide IV on days 1-4 and etoposide
IV continuously on days 5-7. GM-CSF is administered SC (or IV over 4 hours) beginning
on day 8 and continuing until blood counts recover. Patients achieving a second chronic
phase or complete remission proceed to maintenance approximately 4 weeks after hospital
discharge following consolidation.

- Maintenance: Patients receive interferon alfa SC on day 1. Treatment with interferon
alfa continues daily in the absence of disease progression or unacceptable toxicity.

Patients with CNS involvement at entry or who develop CNS disease during the study receive
CNS therapy as outlined below.

- CNS therapy: Patients undergo whole brain irradiation as soon as possible but not
concurrently with mitoxantrone. Patients also receive methotrexate intrathecally 3
times a week until the CSF is clear, weekly for 4 weeks, and then monthly for 6 months.

PROJECTED ACCRUAL: A total of 14-30 patients will be accrued for this study within 4 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of chronic myelogenous leukemia in blast crisis

- Bone marrow blasts at least 20% OR

- Bone marrow blasts plus promyelocytes at least 50%

- Ineligible for higher priority protocols

PATIENT CHARACTERISTICS:

Age:

- 16 and over

Performance status:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Bilirubin less than 2.0 mg/dL

Renal:

- Creatinine less than 2.0 mg/dL

Cardiovascular:

- LVEF greater than 50% by MUGA scan or echocardiogram

Other:

- HIV negative

- Not pregnant

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- Not specified

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- Not specified

Other

- Prior therapy for blast crisis allowed

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Mark Adam Weiss, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

94-070

NCT ID:

NCT00002598

Start Date:

June 1994

Completion Date:

June 2004

Related Keywords:

  • Leukemia
  • relapsing chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • atypical chronic myeloid leukemia, BCR-ABL1 negative
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021