Acute Bilineal Leukemia, Acute Biphenotypic Leukemia, Acute Leukemia of Ambiguous Lineage, Acute Undifferentiated Leukemia, Mixed Phenotype Acute Leukemia, Mixed Phenotype Acute Leukemia, B/Myeloid, Not Otherwise Specified, Mixed Phenotype Acute Leukemia, T/Myeloid, Not Otherwise Specified, Recurrent Mixed Phenotype Acute Leukemia
Conditions
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.
Interventions
DRUGClofarabine
Given IV
DRUGCytarabine
Given IV
DRUGDexamethasone
Given IV
DRUGIdarubicin
Given IV
BIOLOGICALRituximab
Given IV
DRUGSorafenib
Given PO
DRUGSorafenib Tosylate
Given PO
DRUGVincristine
Given IV
DRUGVincristine Sulfate
Given IV
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 4-week Mortality Rate | At 4 weeks | Number of participants who died after 4 weeks of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Combination Chemotherapy) See Detailed Description.
Clofarabine: Given IV
Cytarabine: Given IV
Dexamethasone: Given IV
Idarubicin: Given IV
Rituximab: Given IV
Sorafenib: Given PO
Sorafenib Tosylate: Given PO
Vincristine: Given IV
Vincristine Sulfate: Given IV | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Treatment (Combination Chemotherapy) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 59 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 16 |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 11 / 16 |
Outcome results
Primary
Participants Complete Response
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.
Time frame: Up to 2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Combination Chemotherapy) | Participants Complete Response | 9 Participants |
Secondary
4-week Mortality Rate
Number of participants who died after 4 weeks of treatment.
Time frame: At 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Combination Chemotherapy) | 4-week Mortality Rate | 1 Participants |