Clofarabine, Idarubicin, Cytarabine, Vincristine Sulfate, and Dexamethasone in Treating Patients With Newly Diagnosed or Relapsed Mixed Phenotype Acute Leukemia
Study Details
Study Description
Brief Summary
This phase II trial studies how well clofarabine, idarubicin, cytarabine, vincristine sulfate, and dexamethasone work in treating patients with mixed phenotype acute leukemia that is newly diagnosed or has returned after a period of improvement (relapsed). Drugs used in chemotherapy, such as clofarabine, idarubicin, cytarabine, vincristine sulfate, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVE:
- To evaluate the response rate of the chemotherapy regimen in patients with mixed phenotype acute leukemia.
SECONDARY OBJECTIVE:
- To evaluate the durability of response, the overall and event-free survival rates, and the safety profile of the regimen.
OUTLINE:
INDUCTION THERAPY: Patients receive clofarabine intravenously (IV) over 60 minutes on days 1-4 or 1-3; idarubicin IV over 30-60 minutes on days 1-3 or 1-2; cytarabine IV over 2 hours on days 1-4; vincristine sulfate IV over 15-30 minutes on days 1, 8, and 15; and dexamethasone IV over 10-30 minutes on days 1-4 and 15-18. Patients with a certain type of leukemia may receive rituximab IV over 4-6 hours on days 1 and 8 or sorafenib tosylate orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Patients receive clofarabine IV over 60 minutes on days 1-3 or 1-2; idarubicin IV over 30-60 minutes on days 1-2; cytarabine IV over 2 hours on days 1-3 or 1-2; vincristine sulfate IV over 15-30 minutes on days 1, 8, and 15; and dexamethasone IV over 10-30 minutes on days 1-4 and 15-18. Patients with a certain type of leukemia may receive rituximab IV over 4-6 hours on days 1 and 8 of cycles 1-3 or sorafenib tosylate PO BID on days 1-28 of cycle 1-6 and beyond. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (combination chemotherapy) See Detailed Description. |
Drug: Clofarabine
Given IV
Other Names:
Drug: Cytarabine
Given IV
Other Names:
Drug: Dexamethasone
Given IV
Other Names:
Drug: Idarubicin
Given IV
Other Names:
Biological: Rituximab
Given IV
Other Names:
Drug: Sorafenib
Given PO
Other Names:
Drug: Sorafenib Tosylate
Given PO
Other Names:
Drug: Vincristine
Given IV
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Response (complete response or overall response rate) [Up to 2 months]
The two groups of patients (newly diagnosed or relapsed/refractory) will be evaluated separately. The posterior response rate and their 95% credible intervals will be estimated.
Secondary Outcome Measures
- 4-week mortality rate (Newly diagnosed patients) [At 4 weeks]
For discrete or categorical data, descriptive statistics will include tabulations of frequencies. For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum will be computed.
- Incidence of toxicity (Newly diagnosed patients) [Up to 4 weeks after completion of study treatment]
Will be defined as any grade 3 or greater clinically significant non-hematological toxicity related to treatment. Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. For discrete or categorical data, descriptive statistics will include tabulations of frequencies.
- 4-week mortality rate (Relapsed patients) [At 4 weeks]
- Incidence of toxicity (Relapsed patients) [Up to 4 weeks after completion of study treatment]
Will be defined as any grade 3 or greater clinically significant non hematological toxicity related to treatment. Graded according to NCI CTCAE version 4.0.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Sign an informed consent document
-
Newly diagnosed or relapsed mixed phenotype acute leukemia (MPAL), which for this protocol, will be defined as follows: bone marrow result interpreted by the reading pathologist (or tissue biopsy for cases of extramedullary disease) as: biphenotypic leukemia, bilineal leukemia, undifferentiated leukemia, mixed lineage leukemia, leukemia of ambiguous lineage, T/myeloid leukemia, B/myeloid leukemia, or other diagnosis indicating the presence of multiple lineages within the cell population
-
Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 at study entry
-
Adequate organ function as outlined below (unless due to leukemia)
-
Serum creatinine =< 3 mg/dL
-
Total bilirubin =< 2.5 mg/dL
-
Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and/or aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x upper limit of normal (ULN) or =< 5 x ULN if related to disease
-
Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days; women of childbearing potential and men must agree to use contraception at study entry and for the duration of active study treatment
-
Cardiac ejection fraction >= 40% (by either cardiac echocardiogram [echo] or multi gated acquisition [MUGA] scan); documentation of recent (=< 6 months from screening) outside reports is acceptable
-
If newly diagnosed, prior therapy with hydrea and/or steroid and the use of a single or a two day dose of cytarabine (up to 3 g/m^2), for emergency use up to 24 hours prior to start of study therapy is allowed
Exclusion Criteria:
-
Breast feeding females
-
Patients with active, uncontrolled infections
-
Patients with active secondary malignancy will not be eligible unless approved by the principal investigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Elias Jabbour, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2013-0073
- NCI-2014-02322
- 2013-0073