Flavopiridol and Vorinostat in Treating Patients With Relapsed or Refractory Acute Leukemia or Chronic Myelogenous Leukemia or Refractory Anemia

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. Identifier: NCT00278330
Recruitment Status : Completed
First Posted : January 18, 2006
Last Update Posted : April 2, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase I trial is studying the side effects and best dose of flavopiridol when given together with vorinostat in treating patients with relapsed or refractory acute leukemia or chronic myelogenous leukemia or refractory anemia. Flavopiridol and vorinostat may cause leukemia cells to look more like normal cells, and to grow and spread more slowly. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving flavopiridol together with vorinostat may be an effective treatment for leukemia or refractory anemia.

Condition or disease Intervention/treatment Phase
Blastic Phase Chronic Myelogenous Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Refractory Anemia With Excess Blasts Relapsing Chronic Myelogenous Leukemia Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia Drug: alvocidib Drug: vorinostat Phase 1

Detailed Description:


I. Determine recommended phase II doses for the combination of flavopiridol and vorinostat in patients with acute leukemia, chronic myelogenous leukemia in blast crisis, or refractory anemia with excess blasts-2.


I. Determine the safety, toxicity, tolerability, and maximum tolerated dose of this drug regimen.

II. Determine the pharmacodynamic and clinical anti-leukemic effects of this drug regimen.

III. Correlate leukemia gene expression patterns with response in patients treated with this regimen.

OUTLINE: This is an open-label, dose-escalation study of flavopiridol.

Patients receive flavopiridol IV over 1 hour on days 1-5 and oral vorinostat three times daily on days 1-14. Courses repeat every 21 days 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 2 of 6 patients experience dose-limiting toxicity.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of Vorinostat (SAHA) in Combination With Alvocidib (Flavopiridol) in Patients With Relapsed, Refractory, or (Selected) Poor Prognosis Acute Leukemia or Refractory Anemia With Excess Blasts-2
Study Start Date : January 2006
Actual Primary Completion Date : October 2009

Arm Intervention/treatment
Experimental: Arm I
Patients will receive a 1-hour infusion of flavopiridol on 5 days in week 1 and vorinostat by mouth three times a day in weeks 1 and 2. Treatment may repeat every 3 weeks for as long as benefit is shown.
Drug: alvocidib
Given by infusion
Other Names:
  • flavopiridol
  • HMR 1275
  • L-868275

Drug: vorinostat
Given orally
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza

Primary Outcome Measures :
  1. MTD for the combination of alvocidib and vorinostat, assessed by Common Toxicity Criteria version 3.0 [ Time Frame: 21 days ]

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Diagnosis of one of the following:

    • Relapsed or refractory acute leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], or acute leukemia unclassifiable) following at least one prior systemic treatment
    • Acute leukemia in a patient 60 years or older (no requirement for prior treatment)
    • Acute leukemia that has evolved from a prior myelodysplastic syndrome
    • Chronic myelogenous leukemia (CML) in blast crisis following prior imatinib mesylate therapy
    • Refractory anemia with excess blasts-2 (RAEB-2)
    • No known CNS leukemia
  • ECOG performance status 0-2
  • WBC < 50,000µL
  • Hydroxyurea and/or leukaphereses may be used to lower WBC
  • Creatinine =< 1.5 times upper limit of normal (ULN) OR creatinine clearance >= 50 mL/min
  • Total bilirubin =< 2 times ULN
  • AST/ALT =< 2.5 times ULN
  • QTc interval =< 0.470 seconds
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No other condition that would preclude study participation
  • At least 3 weeks since prior treatment (expect leukaphereses)
  • No valproic acid therapy within the past 2 weeks
  • No prior autologous or allogeneic bone marrow or stem cell transplantation
  • No hydroxyurea use within the past 24 hours
  • No concurrent treatment with other anti-cancer agents or investigational agents

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 identifier (NCT number): NCT00278330

United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Steven Grant Massey Cancer Center

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00278330     History of Changes
Other Study ID Numbers: NCI-2009-00077
MCC 6637
R21CA115260 ( U.S. NIH Grant/Contract )
U01CA062490 ( U.S. NIH Grant/Contract )
First Posted: January 18, 2006    Key Record Dates
Last Update Posted: April 2, 2013
Last Verified: April 2013

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Anemia, Refractory
Blast Crisis
Anemia, Refractory, with Excess of Blasts
Neoplasms by Histologic Type
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Myelodysplastic Syndromes
Cell Transformation, Neoplastic
Neoplastic Processes
Pathologic Processes
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action