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

Recurrent Adult Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00278330
• Other study ID #: NCI-2009-00077
• Secondary ID: MCC 6637CDR00006
• Status: Completed
• Phase: Phase 1
• First received: January 16, 2006
• Last updated: April 1, 2013
• Start date: January 2006

Study information

• Verified date: April 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Anemia, Refractory, with Excess of Blasts
• Blast Crisis
• Blastic Phase Chronic Myelogenous Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• 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

Drug:
• alvocidib
Given by infusion
• vorinostat
Given orally

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD for the combination of alvocidib and vorinostat, assessed by Common Toxicity Criteria version 3.0		21 days	Yes