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Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT00470197

First Posted: May 7, 2007

Last Update Posted: September 30, 2013

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Purpose

Drugs used in chemotherapy, such as flavopiridol, cytarabine, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving a new schedule of more than one drug (combination chemotherapy) may kill more cancer cells. This phase I trial is studying the side effects, best dose, and best schedule for flavopiridol when given together with cytarabine and mitoxantrone in treating patients with relapsed or refractory acute leukemia.

Condition	Intervention	Phase
Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monoblastic Leukemia (M5a) Adult Acute Monocytic Leukemia (M5b) Adult Acute Myeloblastic Leukemia With Maturation (M2) Adult Acute Myeloblastic Leukemia Without Maturation (M1) Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Malignant Neoplasm Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia	Drug: alvocidib Drug: cytarabine Drug: mitoxantrone hydrochloride Other: pharmacological study	Phase 1


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Phase I Study of a Pharmacologically Derived Hybrid Bolus-Infusion Schedule of Flavopiridol (NSC 649890, IND 46,211) Given in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias

Resource links provided by NLM:

MedlinePlus related topics: Leukemia

Drug Information available for: Cytarabine Mitoxantrone Mitoxantrone hydrochloride

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Myeloid Leukemia Acute Myeloblastic Leukemia Without Maturation Acute Myeloblastic Leukemia With Maturation Acute Erythroid Leukemia Acute Megakaryoblastic Leukemia Acute Myelomonocytic Leukemia Di Guglielmo's Syndrome Acute Monoblastic Leukemia Lymphosarcoma Chronic Myeloproliferative Disorders

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose determined by dose-limiting toxicities graded according to NCI-CTC version 3.0 [ Time Frame: Up to 63 days ]


Enrollment:	35
Study Start Date:	April 2007
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients receive flavopiridol IV over 30 minutes on days 1, 2, and 3. Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.	Drug: alvocidib Given IV Other Names: FLAVO flavopiridol HMR 1275 L-868275 Drug: cytarabine Given IV Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside Drug: mitoxantrone hydrochloride Given IV Other Names: CL 232315 DHAD DHAQ Novantrone Other: pharmacological study Correlative study Other Name: pharmacological studies

Detailed Description:

OBJECTIVES:

I. Determine the toxicities of escalating doses of flavopiridol administered by "hybrid" bolus-infusion schedule and given in timed sequence with cytarabine and mitoxantrone hydrochloride in patients with refractory or relapsed acute leukemia.

II. Determine the incidence of clinical response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of flavopiridol. Patients receive flavopiridol IV over 30 minutes on days 1, 2, and 3.

Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and mitoxantrone hydrochloride IV over 60-120 minutes on day 9. Treatment repeats every 35-63 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

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 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Serum and bone marrow samples are collected at baseline, during, and after completion of treatment for future studies. Flavopiridol levels are measured at baseline and on days 1-3 for pharmacokinetics.

Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Pathologically confirmed acute myeloid leukemia or acute lymphoblastic leukemia:
- Relapsed >= 1 time OR refractory disease:
  - Patients who fail primary induction therapy or who relapse after achieving complete remission are eligible if they have received =< 3 prior courses of induction/reinduction therapy
Relapsed >= 1 time OR refractory disease
Patients who fail primary induction therapy or who relapse after achieving complete remission are eligible if they have received =< 3 prior courses of induction/reinduction therapy
No active CNS leukemia
ECOG performance status 0-2
AST and ALT =< 5 times upper limit normal (ULN)
Alkaline phosphatase =< 5 times ULN
Bilirubin =< 2.0 mg/dL
Creatinine =< 2.0 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
LVEF >= 45% by MUGA or ECHO
No active, uncontrolled infection
No other life-threatening illness
No mental deficits and/or psychiatric history that would preclude study compliance
No active graft-vs-host disease
Recovered from all prior therapies
At least 24 hours since prior hydroxyurea, steroids, imatinib mesylate, arsenic trioxide, interferon, or leukapheresis for blast count control
At least 4 weeks since prior stem cell transplantation (autologous or allogeneic)
At least 4 days since prior growth factors
At least 3 weeks since prior chemotherapy, except for non-aplasia producing treatments (e.g., low-dose cyclophosphamide, hydroxyurea, interferon, imatinib mesylate, mercaptopurine, thalidomide, azacitidine, or decitabine)
No prior flavopiridol
No other concurrent chemotherapy, radiotherapy, or immunotherapy
No acute promyelocytic leukemia (M3)
No hyperleukocytosis with > 50,000 blasts/mm^3

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00470197

Locations


United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Judith Karp	Johns Hopkins University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Karp JE, Smith BD, Resar LS, Greer JM, Blackford A, Zhao M, Moton-Nelson D, Alino K, Levis MJ, Gore SD, Joseph B, Carraway H, McDevitt MA, Bagain L, Mackey K, Briel J, Doyle LA, Wright JJ, Rudek MA. Phase 1 and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood. 2011 Mar 24;117(12):3302-10. doi: 10.1182/blood-2010-09-310862. Epub 2011 Jan 14.


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00470197 History of Changes
Other Study ID Numbers:	NCI-2009-00243 NCI-2009-00243 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) J06133 CDR0000543443 J06133 ( Other Identifier: Johns Hopkins University ) 7889 ( Other Identifier: CTEP ) U01CA070095 ( U.S. NIH Grant/Contract ) U01CA062491 ( U.S. NIH Grant/Contract )
First Submitted:	May 3, 2007
First Posted:	May 7, 2007
Last Update Posted:	September 30, 2013
Last Verified:	September 2013

Additional relevant MeSH terms:


Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms Leukemia, Monocytic, Acute Leukemia, Myelomonocytic, Acute Leukemia, Megakaryoblastic, Acute Leukemia, Erythroblastic, Acute Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases	Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Cytarabine Alvocidib Mitoxantrone Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs

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