This research study is for people with a specific type of leukemia called Philadelphia chromosome positive acute lymphoblastic leukemia (the type the patients have). The investigators plan to give you combination of 3 drugs (dasatinib, mitoxantrone, cytarabine) for the first part of the chemotherapy (called Induction). The investigators have previously shown that the combination of mitoxantrone and cytarabine is very effective in your kind of leukemia. The purpose of this study is to establish a safe dose range of dasatinib in combination with this standard induction chemotherapy based on side effects. If possible, the trial will also give us an idea of how well this combination might work in treating your leukemia. Previous studies have shown that dasatinib can produce responses when given alone for your kind of leukemia. By using the dasatinib together with the chemotherapy, the investigators believe that we can kill even more leukemia cells than with either treatment alone. The investigators will initially treat patients with a low dose of dasatinib and monitor for side-effects. If the initial group of patients is able to tolerate this low-dose of dasatinib, then future patients will receive higher doses of dasatinib. Mitoxantrone and cytarabine chemotherapy is the standard therapy at the investigators' institution for the patient's leukemia and it is the combination of dasatinib with this chemotherapy that is new and investigational in this study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
INDUCTION- Dasatinib† (dose levels 1-3) \*continuously Cytarabine 3 g/m2 IV over 3 hours Mitoxantrone 80 mg/m2 IV Myeloid growth factor on day 7 until ANC \> 1,000/μl x 2 days Allopurinol 300 mg BID-TID x 7 days (starting 6-12 hours prior to chemotherapy) Dexamethasone 0.1% eye drops q6h while on cytarabine (start prior to the first dose of cytarabine and continuing at least 24 hours after the last dose) IT Methotrexate 12 mg days 2 and 4 CONSOLIDATION A-Dasatinib† (dose levels 1-3) \*continuously Vincristine 2 mg IV Dexamethasone 10 mg/m2/d days 2 to 29, then taper over 10 days Sulfamethoxazole/Trimethoprim 1 DS BID three times weekly days 2 to 29, then BID daily days 30 to 45 IT Methotrexate 12 mg days 8, 15, 22 and 29
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
To determine the dose of dasatinib that can be safely administered with cytarabine, and high-dose mitoxantrone in patients with Ph+ ALL / lymphoid blast crisis of known chronic myelogenous leukemia.
Time frame: 5 years
To determine the toxicity of this combination in these patients.
Time frame: 5 years
To determine Abl-mutational status at baseline and at the time of disease progression as a possible mechanism of resistance.
Time frame: 5 years
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