Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Antirheumatic Agents

Antipyretics

Fibrinolytic Agents

Analgesics

Platelet Aggregation Inhibitors

Dexamethasone

Cyclophosphamide

Aspirin

Pomalidomide

Dexamethasone acetate

BB 1101

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Angiogenesis Inhibitors

Growth Inhibitors

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).

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).

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).

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.

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

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

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.

Rachid Baz, M.D.

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.

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.

Pomalidomide in Combination With High Dose Dexamethasone and Oral Cyclophosphamide

Evaluation of Pomalidomide in Combination With High Dose Dexamethasone and Oral Cyclophosphamide in Patients With Relapsed and Refractory Myeloma

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.

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.

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.

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

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.

Celgene

H. Lee Moffitt Cancer Center and Research Institute

All participants assigned to Arms A, B, C, plus Arm D group of participants formerly in Arm B (Arm B occurrences listed under B, Arm D occurrences listed under D).

Phase I: Pomalidomide, high dose dexamethasone and oral cyclophosphamide.

A: Dose Escalation of Cyclophosphamide

Phase II: Pomalidomide and high dose dexamethasone.

Crossover Arm D is a part of Arm B. Arm D was opened later to accommodate requested transfers from Arm B. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician.

Arm D participants may be referenced separately in some Outcome Measures.

B: Pomalidomide and Dexamethasone

Phase II: Pomalidomide high dose dexamethasone and oral cyclophosphamide.

C: Pomalidomide, Dexamethasone, Cyclophosphamide

Phase II: Participants who crossed over from Arm B to Arm D.

D: Crossover Arm

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

All participants. Arm D (a part of Arm B) started in July 2012 when, per protocol guidelines, 17 participants from Arm B elected to crossover to Arm D. Some measures may include arm D, making the total of participants evaluated higher.

Phase 2 nature of design may have limited power to detect statistically significant differences in some efficacy outcomes and toxicity measures.

Dr. Rachid Baz

Phase I - Maximum Tolerated Dose (MTD)

Phase II - Overall Response Rate (ORR)

Phase II - Median Progression Free Survival (PFS)

All participants assigned to Arm B and Arm C.

Phase II - Median Overall Survival (OS)

Anemia

Febrile neutropenia

Fatigue

Flu-like symptoms

Lung infection

Sepsis

Upper respiratory infection

Lymphodemia

Neutropenia

Thrombocytopenia

Leukopenia

Hyperglycemia

Hyponatremia

Hypophosphatemia

Hypoxia

Confusion

Pneumonitis

Thromboembolic event

Phase II: Participants who crossed over from Arm B to Arm D. Crossover Arm D is a part of Arm B. Arm D was opened later to accommodate requested transfers from Arm B. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician.

All Phase II Participants who completed allocated intervention.

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

Phase II: Pomalidomide and high dose dexamethasone.

Arm D participants may be referenced separately in some Outcome Measures.

Spots Global Cancer Trial Database for Pomalidomide in Combination With High Dose Dexamethasone and Oral Cyclophosphamide

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial