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

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: January 16, 2006
Last updated: April 1, 2013
Last verified: April 2013
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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

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

Primary Outcome Measures:
  • MTD for the combination of alvocidib and vorinostat, assessed by Common Toxicity Criteria version 3.0 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: January 2006
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00278330     History of Changes
Other Study ID Numbers: NCI-2009-00077  MCC 6637  CDR0000656277  R21CA115260  U01CA062490 
Study First Received: January 16, 2006
Last Updated: April 1, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on May 05, 2016