Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia
This study has been completed.
Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00470197
First received: May 3, 2007
Last updated: September 27, 2013
Last verified: September 2013
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Purpose
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 a new schedule of more than one drug (combination chemotherapy) may kill more cancer cells. This phase I trial is studying the side effects, best dose, and best schedule for flavopiridol when given together with cytarabine and mitoxantrone in treating patients with relapsed or refractory acute leukemia.
| Condition | Intervention | Phase |
|---|---|---|
|
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 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) Adult Acute Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Malignant Neoplasm Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia |
Drug: alvocidib Drug: cytarabine Drug: mitoxantrone hydrochloride Other: pharmacological study |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I Study of a Pharmacologically Derived Hybrid Bolus-Infusion Schedule of Flavopiridol (NSC 649890, IND 46,211) Given in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias |
Resource links provided by NLM:
MedlinePlus related topics:
Leukemia
Genetic and Rare Diseases Information Center resources:
Myeloid Leukemia
Acute Myeloid Leukemia
Acute Non Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia
Acute Myeloblastic Leukemia Without Maturation
Acute Myeloblastic Leukemia With Maturation
Acute Erythroid Leukemia
Acute Megakaryoblastic Leukemia
Acute Myelomonocytic Leukemia
Di Guglielmo's Syndrome
Acute Monoblastic Leukemia
Lymphosarcoma
Chronic Myeloproliferative Disorders
U.S. FDA Resources
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Maximum tolerated dose determined by dose-limiting toxicities graded according to NCI-CTC version 3.0 [ Time Frame: Up to 63 days ]
| Enrollment: | 35 |
| Study Start Date: | April 2007 |
| Primary Completion Date: | January 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
Patients receive flavopiridol IV over 30 minutes on days 1, 2, and 3. Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
|
Drug: alvocidib
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Drug: mitoxantrone hydrochloride
Given IV
Other Names:
Other: pharmacological study
Correlative study
Other Name: pharmacological studies
|
Detailed Description:
OBJECTIVES:
I. Determine the toxicities of escalating doses of flavopiridol administered by "hybrid" bolus-infusion schedule and given in timed sequence with cytarabine and mitoxantrone hydrochloride in patients with refractory or relapsed acute leukemia.
II. Determine the incidence of clinical response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of flavopiridol. Patients receive flavopiridol IV over 30 minutes on days 1, 2, and 3.
Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and mitoxantrone hydrochloride IV over 60-120 minutes on day 9. Treatment repeats every 35-63 days for up to 2 courses 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 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Serum and bone marrow samples are collected at baseline, during, and after completion of treatment for future studies. Flavopiridol levels are measured at baseline and on days 1-3 for pharmacokinetics.
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
-
Pathologically confirmed acute myeloid leukemia or acute lymphoblastic leukemia:
-
Relapsed >= 1 time OR refractory disease:
- Patients who fail primary induction therapy or who relapse after achieving complete remission are eligible if they have received =< 3 prior courses of induction/reinduction therapy
-
- Relapsed >= 1 time OR refractory disease
- Patients who fail primary induction therapy or who relapse after achieving complete remission are eligible if they have received =< 3 prior courses of induction/reinduction therapy
- No active CNS leukemia
- ECOG performance status 0-2
- AST and ALT =< 5 times upper limit normal (ULN)
- Alkaline phosphatase =< 5 times ULN
- Bilirubin =< 2.0 mg/dL
- Creatinine =< 2.0 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- LVEF >= 45% by MUGA or ECHO
- No active, uncontrolled infection
- No other life-threatening illness
- No mental deficits and/or psychiatric history that would preclude study compliance
- No active graft-vs-host disease
- Recovered from all prior therapies
- At least 24 hours since prior hydroxyurea, steroids, imatinib mesylate, arsenic trioxide, interferon, or leukapheresis for blast count control
- At least 4 weeks since prior stem cell transplantation (autologous or allogeneic)
- At least 4 days since prior growth factors
- At least 3 weeks since prior chemotherapy, except for non-aplasia producing treatments (e.g., low-dose cyclophosphamide, hydroxyurea, interferon, imatinib mesylate, mercaptopurine, thalidomide, azacitidine, or decitabine)
- No prior flavopiridol
- No other concurrent chemotherapy, radiotherapy, or immunotherapy
- No acute promyelocytic leukemia (M3)
- No hyperleukocytosis with > 50,000 blasts/mm^3
Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00470197
Please refer to this study by its ClinicalTrials.gov identifier: NCT00470197
Locations
| United States, Maryland | |
| Johns Hopkins University | |
| Baltimore, Maryland, United States, 21287-8936 | |
| United States, Wisconsin | |
| University of Wisconsin Hospital and Clinics | |
| Madison, Wisconsin, United States, 53792 | |
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Judith Karp | Johns Hopkins University |
More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00470197 History of Changes |
| Other Study ID Numbers: |
NCI-2009-00243 NCI-2009-00243 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) J06133 CDR0000543443 J06133 ( Other Identifier: Johns Hopkins University ) 7889 ( Other Identifier: CTEP ) U01CA070095 ( US NIH Grant/Contract Award Number ) U01CA062491 ( US NIH Grant/Contract Award Number ) |
| Study First Received: | May 3, 2007 |
| Last Updated: | September 27, 2013 |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms Leukemia, Monocytic, Acute Leukemia, Myelomonocytic, Acute Leukemia, Erythroblastic, Acute Leukemia, Megakaryoblastic, Acute Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Cytarabine Alvocidib Mitoxantrone Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 25, 2017