Acute Lymphoblastic Leukemia in Complete Remission Clinical Trial
Official title:
Standard Maintenance [POMP/D (Methotrexate, 6 - Mercaptopurine, Vincristine, Prednisone/Dexamethasone)] Plus Ixazomib Maintenance Therapy in Adults With Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma or Mixed Phenotype Acute Leukemia in Complete Remission (CR)
In this phase I study, escalating doses of IXAZOMIB will be combined with the POMP/D regimen.
PRIMARY OBJECTIVE
The primary objective is to determine the maximum-tolerated dose of IXAZOMIB (MLN9708)
(maximum of 4 mg, which is the recommended phase II dose for IXAZOMIB (MLN9708) in
combination with standard maintenance therapy with POMP/D (methotrexate, 6- mercaptopurine,
vincristine, prednisone/dexamethasone) and to assess the tolerability of POMP/D and IXAZOMIB
(MLN9708) maintenance in adult patients with acute lymphoblastic leukemia, lymphoblastic
lymphoma (LBL) or mixed phenotype acute leukemia (MPAL) in complete remission (CR).
SECONDARY OBJECTIVE
To determine the three-year progression-free survival (PFS) of patients treated with oral
IXAZOMIB (MLN9708) and standard maintenance regimen. Progression-free survival will be
measured from the start of induction to disease relapse.
STUDY DESIGN
The maximum-tolerated dose of single agent IXAZOMIB was 1.76 to 2.0mg/m2 when given on a
twice a week schedule1 and > 2.34 mg/m2 to 2.97 mg/m2 on a weekly schedule in previous
studies.
Three patients will be treated per dose level unless dose-limiting toxicity (DLT) is
observed. The starting dose of IXAZOMIB will be 3 mg orally on days 1, 8 and 15. If no DLT is
seen in the first three patients, the dose will be increased to 4 mg on days 1, 8 and 15 in a
classic 3 +3 phase I design. We will not attempt to increase the dose beyond 4 mg orally
which, if achieved with acceptable toxicity, would be accepted as the recommended phase 2
dose (RP2D). Zero of three DLTs would allow escalation to the next dose level. One of three
DLTs will require expanding to six patients; one of six DLTs will allow escalation again. Two
DLTs will require dose de-escalation. The maximum-tolerated dose (MTD) will be the highest
dose administered at which no more than one DLT was observed.
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