Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Study Details
Study Description
Brief Summary
This phase II trial is studying the side effects and how well giving alvocidib together with cytarabine and mitoxantrone works in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as alvocidib, 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.
Detailed Description
PRIMARY OBJECTIVES:
-
To determine the efficacy and toxicities of flavopiridol (alvocidib) followed by ara-C and mitoxantrone in adults with newly diagnosed acute myelogenous leukemia (AML) with poor-risk features.
-
To determine the disease free and overall survival of patients exhibiting a response to treatment with flavopiridol followed by ara-C and mitoxantrone.
OUTLINE:
Patients receive alvocidib 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment (alvocidib, cytarabine, mitoxantrone hydrochloride) Patients receive alvocidib 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. |
Drug: alvocidib
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Drug: mitoxantrone hydrochloride
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Complete Response [6 months]
Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an Absolute Neutrophil Count of at least 1000/mililiter and a platelet count of 100,000 mililiter, 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 complete remission 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 complete remission.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adults with established, pathologically confirmed diagnoses of newly diagnosed, poor-risk Acute Myeloid Leukemia(AML) including de novo and secondary Acute Myeloid Leukemias but excluding newly diagnosed acute progranulocytic leukemia (APL, M3) will be considered eligible for study
-
ECOG performance status 0-2
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Patient must be able to give informed consent
-
Serum creatinine =< 2.0
-
ALT, AST =< 5 x upper limit of normal
-
Bilirubin =< 2.0 mg/dl
-
Left ventricular ejection fraction >= 45%
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Newly diagnosed AML, subtypes M0,1,2,4-7 but excluding M3 (APL) with poor-risk features, including:
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Age > 50 years, or age > 18 years with one or more of the following criteria:
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Antecedent hematologic disorder including myelodysplasia (MDS)-related AML (MDS/AML) and prior myeloproliferative disorder (MPD)
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Treatment-related AML
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AML with trilineage dysplasia (AML-TLD)
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Adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q, 21q or 17p; t(6;9); t(9;22); trisomy 8; trisomy 13, complex karyotypes (>= 3 unrelated abnormalities)
Exclusion Criteria:
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Patients who have received hydroxyurea alone or have received non-cytotoxic therapies previously for MDS or MPD (e.g., thalidomide or lenalidomide, interferon, cytokines, low-dose 5-azacytidine, low-dose cytoxan) will be eligible for this trial
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Any previous treatment with flavopiridol
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Concomitant chemotherapy, radiation therapy, or immunotherapy
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Hyperleukocytosis with >= 50,000 blasts/uL; leukapheresis or hydroxyurea may be used immediately prior to study drug administration for cytoreduction; must be stopped 24 hours before first dose of Flavopiridol
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Acute Progranulocytic Leukemia (APL, M3)
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Active CNS leukemia
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Active, uncontrolled infection; patients with infection under active treatment and controlled with antibiotics are eligible
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Presence of other life-threatening illness
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Patients with mental deficits and/or psychiatric history that preclude them form giving informed consent or from following protocol
-
Pregnant and nursing patients are excluded
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Judith Karp, Johns Hopkins University/Sidney Kimmel Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2012-02986
- NCI-2012-02986
- U01CA070095
- P30CA006973
- J0669
- 7845
Study Results
Participant Flow
Recruitment Details | From December 2006 through June 2008 |
---|---|
Pre-assignment Detail |
Arm/Group Title | Arm A |
---|---|
Arm/Group Description | Flavopiridol, ara-C, mitoxantrone |
Period Title: Overall Study | |
STARTED | 45 |
CR | 30 |
COMPLETED | 45 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Arm A |
---|---|
Arm/Group Description | Flavopiridol, ara-C, mitoxantrone |
Overall Participants | 45 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
32
71.1%
|
>=65 years |
13
28.9%
|
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
61
(50)
|
Sex: Female, Male (Count of Participants) | |
Female |
22
48.9%
|
Male |
23
51.1%
|
Region of Enrollment (participants) [Number] | |
United States |
45
100%
|
Outcome Measures
Title | Complete Response |
---|---|
Description | Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an Absolute Neutrophil Count of at least 1000/mililiter and a platelet count of 100,000 mililiter, 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 complete remission 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 complete remission. |
Time Frame | 6 months |
Outcome Measure Data
Analysis Population Description |
---|
Total number of participants entered between December 2006 and June 2008 |
Arm/Group Title | Arm A |
---|---|
Arm/Group Description | Flavopiridol, ara-C, mitoxantrone |
Measure Participants | 45 |
Number [participants] |
45
100%
|
Adverse Events
Time Frame | Adverse events were collected from the time of treatmetn through recovery of blood counts and response assessment | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Arm A | |
Arm/Group Description | Flavopiridol, ara-C, mitoxantrone | |
All Cause Mortality |
||
Arm A | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
Arm A | ||
Affected / at Risk (%) | # Events | |
Total | 19/45 (42.2%) | |
Cardiac disorders | ||
cardiac dysfunction | 7/45 (15.6%) | 7 |
Investigations | ||
Desseminated Intravascular Coagulopathy | 3/45 (6.7%) | 3 |
Metabolism and nutrition disorders | ||
Tumor lysis syndrome | 19/45 (42.2%) | 19 |
Other (Not Including Serious) Adverse Events |
||
Arm A | ||
Affected / at Risk (%) | # Events | |
Total | 25/45 (55.6%) | |
Gastrointestinal disorders | ||
oral mucositis | 14/45 (31.1%) | 14 |
Diarrhea | 11/45 (24.4%) | 11 |
GI Mucositis | 5/45 (11.1%) | 5 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | Judith Karp, MD |
---|---|
Organization | SKCCC |
Phone | 410-502-7726 |
jkarp2@jhmi.edu |
- NCI-2012-02986
- NCI-2012-02986
- U01CA070095
- P30CA006973
- J0669
- 7845