Clinical trial NCT01432600
Conditions: Myeloma
Keywords: Multiple Myeloma Relapsed Refractory Corticosteroids
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Start date: 2011-11-01; Completion date: 2016-08-01
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The main purpose of this study is to see whether pomalidomide can help people with myeloma. Researchers also want to find out if pomalidomide is safe and tolerable.

Detailed description:
There are two parts to this study:

* Phase 1: To determine a safe dose of the medication cyclophosphamide in combination with pomalidomide and dexamethasone.
* Phase 2: To see the difference in effectiveness of pomalidomide in combination with high dose dexamethasone with or without cyclophosphamide for the treatment of participants who have myeloma, which has relapsed to or become refractory (not responding) to prior treatment.

Arms: arm 1: Phase I: Pomalidomide, high dose dexamethasone and oral cyclophosphamide:

Pomalidomide 4 mg by mouth (PO) days 1-21 of a 28 days cycle.

Dexamethasone 40\* mg PO days 1- 4, 15-18 of a 28 days cycle for the first 4 cycles and subsequently 40 mg PO Days 1,8,15, 22. \*Participants who were \>75 years of age or those who were known to be intolerant to 40 mg weekly dexamethasone received 20 mg dexamethasone on the same schedule.

Dose Escalation of Cyclophosphamide, orallly (PO) days 1, 8, 15 as follows:

Level 1: 300 mg; Level 2: 400 mg; Level 3: 500 mg.

Aspirin 81 mg PO daily (unless the participants had contraindications or were receiving other form of anticoagulation for other indications). arm 2: Randomized Phase II - Pomalidomide high dose dexamethasone:

Pomalidomide 4 mg PO days 1-21 of a 28 days cycle.

Dexamethasone 40\* mg PO Days 1,8,15, 22. \*Participants who were \>75 years of age or those who were known to be intolerant to 40 mg weekly dexamethasone received 20 mg dexamethasone on the same schedule.

Aspirin 81 mg PO daily (unless the participants had contraindications or were receiving other form of anticoagulation for other indications). arm 3: Randomized Phase II - Pomalidomide high dose dexamethasone and oral cyclophosphamide:

Pomalidomide 4 mg PO days 1-21 of a 28 days cycle.

Dexamethasone 40\* mg PO days 1- 4, 15-18 of a 28 days cycle for the first 4 cycles and subsequently 40 mg PO Days 1,8,15, 22. \*Participants who were \>75 years of age or those who were known to be intolerant to 40 mg weekly dexamethasone received 20 mg dexamethasone on the same schedule.

Cyclophosphamide 400 mg PO days 1, 8, 15.

Aspirin 81 mg PO daily (unless the participants had contraindications or were receiving other form of anticoagulation for other indications). arm 4: Crossover from Arm B to Arm D. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician, in which case oral weekly Cyclophosphamide (400 mg orally on days 1, 8, and 15) was added to their tolerated dose of pomalidomide and dexamethasone.
Interventions: intervention 1: Pomalidomide intervention 2: Dexamethasone intervention 3: Cyclophosphamide
Intervention descriptions: intervention 1: Pomalidomide at 4 mg by mouth (PO) as outlined in the treatment arms. intervention 2: Dexamethasone at 40 mg (20 mg) PO as outlined in the treatment arms. intervention 3: The dose escalation uses a standard "3x3" design: Ex: If none of the first 3 participants have a DLT, enter 3 participants at the next higher dose level. Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone was determined, investigators proceeded with the second phase of the trial, a randomized phase II study comparing pomalidomide and dexamethasone with pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.

Protocol documents: