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

Study Overview
=================
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.

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

Conditions
-----------------
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

Intervention / Treatment
-----------------
* Drug: alvocidib
* Drug: vorinostat


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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<br>* Given by infusion<br>* Other names: L-868275;Drug: vorinostat<br>* Given orally<br>* Other names: Zolinza;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD for the combination of alvocidib and vorinostat, assessed by Common Toxicity Criteria version 3.0 |  | 21 days |