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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Patients who have been on stable doses of 6 - MP, vincristine, and methotrexate for a minimum of eight weeks and have at least six months remaining of maintenance are eligible to receive Ixazomib, which will be administered on days 1, 8 and 15.
Froedtert & the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Maximum tolerated dose of ixazomib with POMP/D maintenance
The patient cohort enrolled at each dose level will be monitored for dose-limiting toxicity for eight weeks prior to enrolling the next cohort of patients at a new dose level. Subsequent patient cohorts will be enrolled at doses according to the CRM design. A maximum sample size of 12 patients will be enrolled over four potential doses to determine the maximum tolerated dose of ixazomib with POMP/D maintenance. Adverse events will be summarized with descriptive statistics at each dose level of ixazomib.
Time frame: Eight (8) weeks
Progression-free survival of patients treated with oral Ixazomib and standard maintenance regimen.
Progression-free survival will be measured from the time of diagnosis to disease relapse.
Time frame: Three (3) years
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