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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

Phase 1
18 Years
Not Enrolling
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

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Trial Information

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


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

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

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.

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

- 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 < 50,000┬ÁL

- Hydroxyurea and/or leukaphereses may be used to lower WBC

- Creatinine =< 1.5 times upper limit of normal (ULN) OR creatinine clearance >= 50

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

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

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Steven Grant

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massey Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

January 2006

Completion Date:

Related Keywords:

  • 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
  • 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



Virginia Commonwealth UniversityRichmond, Virginia