Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
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Purpose
RATIONALE: Drugs used in chemotherapy, such as flavopiridol, cytarabine, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase II trial is studying the side effects and how well giving flavopiridol together with cytarabine and mitoxantrone works in treating patients with newly diagnosed acute myeloid leukemia.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia |
Drug: alvocidib Drug: cytarabine Drug: mitoxantrone hydrochloride |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
- Complete Response [ Time Frame: 6 months ] [ Designated as safety issue: No ]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.
| Enrollment: | 46 |
| Study Start Date: | October 2006 |
| Study Completion Date: | August 2009 |
| Primary Completion Date: | July 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm A
Flavopiridol, ara-C, mitoxantrone
|
Drug: alvocidib
alvocib IV Days 1-3
Other Name: flavopiridol
Drug: cytarabine
cytarabine IV 72 hr infusion D6-8
Other Name: ara-C
Drug: mitoxantrone hydrochloride
Mitoxantrone IV D9
Other Name: novantrone
|
Detailed Description:
OBJECTIVES:
Primary
- Determine the efficacy of flavopiridol, cytarabine, and mitoxantrone hydrochloride, in terms of complete response, in patients with newly diagnosed, poor-risk acute myeloid leukemia.
- 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed acute myeloid leukemia (AML), including the following subtypes:
- M0
- M1
- M2
- M4
- M5
- M6
- M7
Newly diagnosed de novo or secondary AML with ≥ 1 of the following poor-risk features:
- 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
PATIENT CHARACTERISTICS:
- 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 participation
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- Prior chemotherapy or bone marrow/stem cell transplant for a non-AML malignancy allowed
- 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
Contacts and Locations| United States, Maryland | |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | |
| Baltimore, Maryland, United States, 21231-2410 | |
| Study Chair: | Judith E. Karp, MD | Sidney Kimmel Comprehensive Cancer Center |
More Information
No publications provided by National Cancer Institute (NCI)
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00407966 History of Changes |
| Other Study ID Numbers: | NCI-2012-02986, U01CA70095, P30CA06973, J0669 |
| Study First Received: | December 4, 2006 |
| Results First Received: | May 1, 2012 |
| Last Updated: | January 8, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Cancer Institute (NCI):
|
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) |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Neoplasms by Histologic Type Neoplasms Cytarabine Flavopiridol Mitoxantrone Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses |
Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents Central Nervous System Agents Growth Inhibitors Growth Substances Protein Kinase Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013