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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00278330
First received: January 16, 2006
Last updated: April 1, 2013
Last verified: April 2013
  Purpose

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:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Drug: vorinostat
Given orally
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza

Detailed Description:

PRIMARY OBJECTIVE:

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.

SECONDARY OBJECTIVES:

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.

  Eligibility

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

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00278330

Locations
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Grant Massey Cancer Center
  More Information

No publications provided

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

ClinicalTrials.gov processed this record on July 29, 2014