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

Primary Purpose

Blastic Phase Chronic Myelogenous Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
alvocidib
vorinostat
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Blastic Phase Chronic Myelogenous Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Virginia Commonwealth University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

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.

Outcomes

Primary Outcome Measures

MTD for the combination of alvocidib and vorinostat, assessed by Common Toxicity Criteria version 3.0

Secondary Outcome Measures

Full Information

First Posted
January 16, 2006
Last Updated
April 1, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00278330
Brief Title
Flavopiridol and Vorinostat in Treating Patients With Relapsed or Refractory Acute Leukemia or Chronic Myelogenous Leukemia or Refractory Anemia
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 Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
alvocidib
Other Intervention Name(s)
FLAVO, flavopiridol, HMR 1275, L-868275
Intervention Description
Given by infusion
Intervention Type
Drug
Intervention Name(s)
vorinostat
Other Intervention Name(s)
L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
MTD for the combination of alvocidib and vorinostat, assessed by Common Toxicity Criteria version 3.0
Time Frame
21 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Grant
Organizational Affiliation
Massey Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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