Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia - Full Text View

Sponsor:	Sidney Kimmel Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00016016

Purpose

RATIONALE: Drugs used in chemotherapy work in 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 flavopiridol and cytarabine with mitoxantrone in treating patients who have acute leukemia.

Condition	Intervention	Phase
Leukemia	Drug: alvocidib Drug: cytarabine Drug: mitoxantrone hydrochloride	Phase II

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia

Drug Information available for: Cytarabine hydrochloride Mitoxantrone Mitoxantrone hydrochloride Alvocidib Flavopiridol Cytarabine

U.S. FDA Resources

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:

Complete remission (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment:	53
Study Start Date:	February 2001
Study Completion Date:	May 2007
Primary Completion Date:	November 2006 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

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

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.

PROJECTED ACCRUAL: 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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/mm^3
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

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00016016

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Judith E. Karp, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

Publications:

Karp JE, Passaniti A, Gojo I, Kaufmann S, Bible K, Garimella TS, Greer J, Briel J, Smith BD, Gore SD, Tidwell ML, Ross DD, Wright JJ, Colevas AD, Bauer KS. 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. 2005 Dec 1;11(23):8403-12.

ClinicalTrials.gov Identifier:	NCT00016016 History of Changes
Other Study ID Numbers:	CDR0000068582, J0254, U01CA069854, P30CA006973, JHOC-J0254, MSGCC-0052, NCI-3170
Study First Received:	May 6, 2001
Last Updated:	July 19, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:

recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia

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)

Additional relevant MeSH terms:

Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Flavopiridol
Mitoxantrone
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents

Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Growth Inhibitors
Growth Substances
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012