Pomalidomide in Combination With High Dose Dexamethasone and Oral Cyclophosphamide

Browse trials for

• Multiple Myeloma 3,632
• Neoplasms, Plasma Cell 2,306

Keywords

• Multiple Myeloma
• Relapsed
• Refractory
• Corticosteroids

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 80 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Lead sponsor

H. Lee Moffitt Cancer Center and Research Institute is the lead sponsor of 533 studies on the registry; 74 are open to participants now.

Of its 99 completed or terminated interventional studies of FDA-regulated products, 57 (58%) have results posted.

Study arms

• Experimental
  A: Dose Escalation of Cyclophosphamide

  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).

  Drug: Pomalidomide · Drug: Dexamethasone · Drug: Cyclophosphamide

• Active comparator
  B: Pomalidomide and Dexamethasone

  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).

  Drug: Pomalidomide · Drug: Dexamethasone

• Active comparator
  C: Pomalidomide/Dexamethasone/Cyclophosphamide

  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).

  Drug: Pomalidomide · Drug: Dexamethasone · Drug: Cyclophosphamide

• Other
  D: Crossover

  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.

  Drug: Pomalidomide · Drug: Dexamethasone · Drug: Cyclophosphamide

Interventions

• DrugPomalidomide

  Pomalidomide at 4 mg by mouth (PO) as outlined in the treatment arms.

  Also known as: CC-4047, POMALYST®

• DrugDexamethasone

  Dexamethasone at 40 mg (20 mg) PO as outlined in the treatment arms.

  Also known as: Decadron®

• DrugCyclophosphamide

  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.

  Also known as: Cytoxan

Primary outcomes

1. Phase I - Maximum Tolerated Dose (MTD)

   The maximum tolerated dose of oral weekly cyclophosphamide in milligrams (mg), in combination with pomalidomide and dexamethasone. Dose Escalation of Cyclophosphamide, orallly (PO) days 1, 8, 15 as follows: Level 1: 300 mg; Level 2: 400 mg; Level 3: 500 mg. The period for assessment of Dose Limiting Toxicity (DLT) is the first cycle (28 days). The following toxicities will be considered dose limiting if encountered only in the phase I portion of the study: Febrile neutropenia; Grade 3 or 4 non-hematologic toxicity related to treatment with pomalidomide or cyclophosphamide; Participants must have received optimal symptomatic treatment for Grade 3 or 4 nausea, vomiting, or diarrhea to be considered a DLT; Grade 4 transaminitis; Grade 3 transaminitis must be present for ≥ 7 days to be considered a DLT; Grade 4 thrombocytopenia for 7 or more days; Grade 4 neutropenia for 7 or more days.

   Time frame: 28 Days

2. Phase II - Overall Response Rate (ORR)

   Overall response, Minimal Remission (MR) or better per treatment arm, using the uniform response criteria by the International Myeloma Working Group (IMWG) of pomalidomide in combination with high dose dexamethasone with or without cyclophosphamide in participants with relapsed and refractory myeloma. In addition, Minimal response was incorporated in those response criteria as this is a valid endpoint in patients with relapsed or refractory myeloma. MR: 25-49% reduction in serum paraprotein and a 50-89% reduction in urine light chain excretion; A 25-49% reduction in the size of soft tissue plasmacytoma must be demonstrated is applicable.

   Time frame: 36 Months

Secondary outcomes

1. Phase II - Median Progression Free Survival (PFS)

   Progression free survival per treatment arm. Progressive Disease (PD) requires one of the following, increase of greater than or equal to 25% from baseline in: Serum M-component; Urine M-component; The difference between involved and uninvolved sFLC levels; The size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia.

   Time frame: 36 Months

2. Phase II - Median Overall Survival (OS)

   Overall survival per treatment arm. Overall survival is defined as the time from start of treatment to death of any cause.

   Time frame: 36 Months

3. Phase II - Occurrence of Possibly Related Adverse Events (AEs)

   Phase II: Participants with Grade 3 or 4 adverse events at least possibly related to the study treatment in 5% of participants in the Phase 2 portion, by AE category, assessed by the National Cancer Institute Common Terminology Criteria (NCI CTC) version 4.0.

   Time frame: Up to 48 Months

Baseline characteristics

Publications

• Baz RC, Martin TG 3rd, Lin HY, Zhao X, Shain KH, Cho HJ, Wolf JL, Mahindra A, Chari A, Sullivan DM, Nardelli LA, Lau K, Alsina M, Jagannath S. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016 May 26;127(21):2561-8. doi: 10.1182/blood-2015-11-682518. Epub 2016 Mar 1. PubMed 26932802 ↗