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Phase II Study of Flavopiridol (NSC 649890, IND 46, 211) in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Newly Diagnosed, Previously Untreated, Poor- Risk Acute Myelogenous Leukemia

Phase 2
18 Years
Not Enrolling

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Trial Information

Phase II Study of Flavopiridol (NSC 649890, IND 46, 211) in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Newly Diagnosed, Previously Untreated, Poor- Risk Acute Myelogenous Leukemia



- Determine the efficacy of flavopiridol, cytarabine, and mitoxantrone hydrochloride, in
terms of complete response, in patients with newly diagnosed, poor-risk acute myeloid

- Determine the toxicity of this regimen in these patients.

OUTLINE: Patients receive flavopiridol IV over 1 hour on days 1-3, cytarabine IV
continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on
day 9. Beginning 35-63 days after completion of course 1, patients achieving complete or
partial remission may receive a second course of treatment as above.

Patients age 50 and over with "core binding factor" acute myeloid leukemia (AML) (e.g.,
t[8;21], inv[16], or t[16;16]) achieving a complete remission after course 1 of treatment
may receive 3-4 courses of consolidation therapy comprising high-dose cytarabine at the
discretion of the investigator.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Inclusion Criteria


- Histologically confirmed acute myeloid leukemia (AML), including the following

- M0

- M1

- M2

- M4

- M5

- M6

- M7

- Newly diagnosed de novo or secondary AML with ≥ 1 of the following poor-risk

- Antecedent hematologic disorder (e.g., myelodysplasia-related AML or prior
myeloproliferative disorder)

- Treatment-related AML

- AML with trilineage dysplasia

- AML with adverse cytogenetics, including any of the following:

- -5/-5q

- -7/-7q

- Abnormal 3q, 9q, 11q, 20q, 21q, or 17p

- t(6;9)

- t(9;22)

- Trisomy 8

- Trisomy 13

- Complex karyotypes (i.e., ≥ 3 unrelated abnormalities)

- No acute promyelocytic leukemia (M3 AML)

- No hyperleukocytosis (≥ 50,000 blasts/µL)

- Leukophoresis or hydroxyurea is allowed immediately prior to study drug
administration for cytoreduction and provided it is stopped 24 hours before
first dose of flavopiridol

- No active CNS leukemia


- ECOG performance status 0-2

- Creatinine ≤ 2.0 mg/dL

- AST and ALT ≤ 5 times upper limit of normal

- Bilirubin ≤ 2.0 mg/dL

- LVEF ≥ 45 %

- No active, uncontrolled infection (actively treated and antibiotic-controlled
infection allowed)

- No other life-threatening illness

- No mental deficiencies or psychiatric disorder that would preclude study

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception


- Prior chemotherapy or bone marrow/stem cell transplant for a non-AML malignancy

- No prior treatment except hydroxyurea alone or noncytotoxic therapies for
myelodysplastic syndromes or myeloproliferative disorders (e.g., thalidomide,
lenidomide, interferon, cytokines, low-dose azacitidine, low-dose cyclophosphamide,
or arsenic trioxide)

- No prior flavopiridol

- No other concurrent chemotherapy, radiotherapy, or immunotherapy

- No other concurrent anticancer agents or therapies

Type of Study:


Study Design:

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

Outcome Measure:

Complete Response

Outcome Description:

Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/L and a platelet count of 100,000 L, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. A CR must be confirmed 4 to 6 weeks after the initial documentation. If possible, at least one bone marrow biopsy should be performed to confirm the CR.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Judith E. Karp, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2006

Completion Date:

August 2009

Related Keywords:

  • Leukemia
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • secondary acute myeloid leukemia
  • untreated adult acute myeloid leukemia
  • adult acute basophilic leukemia
  • adult acute eosinophilic leukemia
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute minimally differentiated myeloid leukemia (M0)
  • adult acute monoblastic leukemia (M5a)
  • adult acute monocytic leukemia (M5b)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myelomonocytic leukemia (M4)
  • adult erythroleukemia (M6a)
  • adult pure erythroid leukemia (M6b)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410