Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI JHOC-J0254 MSGCC-0052, NCI-3170, NCT00016016

Objectives

1. Determine the toxic effects of escalating doses of flavopiridol administered with cytarabine and mitoxantrone in patients with poor-risk acute leukemias.
2. Determine whether this treatment induces clinical responses in these patients.
3. Determine whether flavopiridol is directly cytotoxic to leukemic blasts in these patients.
4. Determine whether flavopiridol can recruit and synchronize residual leukemic blasts to proliferate in these patients.

Entry Criteria

Disease Characteristics:

• One of the following histologically confirmed poor-risk acute leukemias:
  • Acute myelogenous leukemia (AML)
    • AML arising from myelodysplastic syndromes (MDS)
    • Secondary AML
    • Relapsed or refractory AML, including primary induction failure
  • Acute lymphoblastic leukemia (ALL)
    • Relapsed or refractory ALL, including primary induction failure



• No hyperleukocytosis with at least 50,000 leukemic blasts/mm³



• Failure of primary induction therapy or relapse after achieving complete remission allowed if completed no more than 3 prior courses of induction/reinduction therapy



• No active CNS leukemia

Prior/Concurrent Therapy:

Biologic therapy:

• Prior autologous or allogeneic stem cell transplantation allowed provided at least 4 weeks since treatment and no presence of active graft-vs-host disease
• At least 4 days since prior hematopoietic growth factors (e.g., epoetin alfa, filgrastim [G-CSF], sargramostim [GM-CSF], interleukin-3, or interleukin-11)
• Prior interferon allowed
• No concurrent immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior intensive chemotherapy except non-aplasia-producing agents (e.g., hydroxyurea or 6-methylpurine) and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• Prior thalidomide or imatinib mesylate allowed
• No other concurrent investigational or commercially-available antitumor therapy

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• No disseminated intravascular coagulation

Hepatic:

• AST and ALT no greater than 2.5 times normal
• Alkaline phosphatase no greater than 2.5 times normal
• Bilirubin no greater than 1.5 times normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No intrinsic impaired cardiac function including the following:
  • Myocardial infarction within the past 3 months
  • History of congestive heart disease or arrhythmia (regardless of time, severity, or resolution)
  • Cardiomyopathy
  • Class III or IV congestive heart failure
• LVEF at least 45% by MUGA or echocardiogram

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active uncontrolled infection

Expected Enrollment

Approximately 25-35 patients will be accrued for phase I of the study (phase I closed to accrual effective 10/24/2003). A total of 53 patients will be accrued for phase II of the study.

Outcomes

Complete remission (Phase II)

Outline

This is a dose-escalation study of flavopiridol. (Phase I closed to accrual effective10/24/2003).

Patients receive flavopiridol IV over 1 hour on days 1-3 and cytarabine IV continuously on days 6-9 followed by mitoxantrone IV over 30-150 minutes on day 9. Patients achieving a partial or complete response after the first course of therapy may receive an additional course of therapy beginning 35 ± 7 days after blood count recovery.

Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. (Phase I closed to accrual effective 10/24/2003). Once the MTD is reached, additional patients are accrued to receive flavopiridol at the recommended phase II dose.

Karp JE, Passaniti A, Gojo I, et al.: Phase I and pharmacokinetic study of flavopiridol followed by 1-beta-D-arabinofuranosylcytosine and mitoxantrone in relapsed and refractory adult acute leukemias. Clin Cancer Res 11 (23): 8403-12, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Judith Karp, MD, Protocol chair		Ph: 410-502-7726

Registry Information
Official Title		A Phase I/II Study of Flavopiridol (NSC 649890, IND 46,211) in Timed Sequential Combination with Cytosine Arabinoside (ara-C) and Mitoxantrone for Adults with Poor-Risk Acute Leukemias
Trial Start Date		2001-02-23
Registered in ClinicalTrials.gov		NCT00016016
Date Submitted to PDQ		2001-03-02
Information Last Verified		2006-11-07
NCI Grant/Contract Number		CA69854

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