Incidence, Type and Severity of Adverse Events, Graded According to National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE) Version 4.0 (Phase II)

Phase II Arm I (Pomalidomide, Dexamethasone)

Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.

Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib) + Crossover Patients From Arm I

Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Phase 1 Dose Level 1

A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age \> 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 1 was 2mg POM-DEX and 3mg IXA.

Phase 1 Dose Level 2

A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age \> 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 2 was 3mg POM-DEX and 3mg IXA.

Phase 1 Dose Level 3

A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age \> 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 3 was 4mg POM-DEX and 3mg IXA.

Phase 1 Dose Level 4

A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age \> 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 4 was 4mg POM-DEX and 4mg IXA.

Analysis denominator · Participants