Clofarabine, Idarubicin, Cytarabine, Vincristine Sulfate, and Dexamethasone in Treating Patients With Newly Diagnosed or Relapsed Mixed Phenotype Acute Leukemia

Phase 2

Completed

Conditions: Acute Undifferentiated Leukemia
Acute Leukemia of Ambiguous Lineage
Mixed Phenotype Acute Leukemia, B/Myeloid, Not Otherwise Specified
Mixed Phenotype Acute Leukemia
Mixed Phenotype Acute Leukemia, T/Myeloid, Not Otherwise Specified
Acute Bilineal Leukemia
Acute Biphenotypic Leukemia
Recurrent Mixed Phenotype Acute Leukemia

Interventions: Drug: Clofarabine
Drug: Cytarabine
Drug: Dexamethasone
Drug: Idarubicin
Biological: Rituximab
Drug: Sorafenib
Drug: Sorafenib Tosylate
Drug: Vincristine
Drug: Vincristine Sulfate

Registration Number: NCT02135874

Lead Sponsor: M.D. Anderson Cancer Center

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.

Detailed Description: PRIMARY OBJECTIVE:

I. To evaluate the response rate of the chemotherapy regimen in patients with mixed phenotype acute leukemia.

SECONDARY OBJECTIVE:

I. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (combination chemotherapy)	Rituximab	See Detailed Description.
Treatment (combination chemotherapy)	Vincristine	See Detailed Description.
Treatment (combination chemotherapy)	Vincristine Sulfate	See Detailed Description.
Treatment (combination chemotherapy)	Sorafenib Tosylate	See Detailed Description.
Treatment (combination chemotherapy)	Clofarabine	See Detailed Description.
Treatment (combination chemotherapy)	Cytarabine	See Detailed Description.
Treatment (combination chemotherapy)	Dexamethasone	See Detailed Description.
Treatment (combination chemotherapy)	Idarubicin	See Detailed Description.
Treatment (combination chemotherapy)	Sorafenib	See Detailed Description.

Primary Outcome Measures

Name	Time	Method
Participants Complete Response	Up to 2 months	Response is Complete Response (CR) is Neutrophil count \>/= 1.0 x 10\^9/L, . Platelet count \>/= 100 x 10\^9/L, Bone marrow aspirate \< 5% blasts, No extramedullary leukemia.

Secondary Outcome Measures