Study of Pomalidomide, Cyclophosphamide, Dexamethasone in Relapsed/Refractory Multiple Myeloma

Sponsor

Ajai Chari (Other)

Overall Status

Completed

CT.gov ID

NCT02176213

Collaborator

Celgene Corporation (Industry)

Enrollment

Location

Arm

59.2

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is being done to learn more about the drug, pomalidomide and to gather data on its safety and side effects when used in combination with commercially available cyclophosphamide and dexamethasone. This combination is considered experimental and has not been approved by the FDA.

Pomalidomide is a third generation immunomodulatory (IMiDs) agent, which is a more potent version of thalidomide and lenalidomide drugs that have been approved by the United States Food and Drug Administration [FDA] for the treatment of MM. In February 2013, pomalidomide was also approved by the FDA for patients with MM who have had more than 2 types of therapy.

Pomalidomide is taken orally as capsules, and cyclophosphamide and dexamethasone are also taken orally as tablets in this study. Cyclophosphamide and dexamethasone are commercially available and are often used in combination with other drugs to treat Multiple Myeloma. Preliminary data from both the laboratory and patient studies suggest that this combination of drugs is more effective than pomalidomide and dexamethasone alone. However, the regimen being used in this study, which consists of daily cyclophosphamide, also permits support of low blood counts with either injections or transfusions as needed.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma in Relapse Multiple Myeloma, Refractory	Drug: Pomalidomide Drug: Cyclophosphamide Drug: Dexamethasone	Phase 2

Detailed Description

This is an open label, single center, phase II study of a combination of pomalidomide, daily low dose oral cyclophosphamide, and dexamethasone in patients with relapsed/refractory multiple myeloma. The three oral drugs will be given in 28-day cycles: Pomalidomide 4 mg daily x 21 days; cyclophosphamide 50 mg BID x 21 days; and dexamethasone 40 mg weekly x 3 (20 mg weekly if the patient aged ≥ 75 years old). Subjects meeting eligibility criteria with ANC < 1000/µL and platelet count < 50,000/µL will start at dose level -1 of both pomalidomide (3 mg daily) and cyclophosphamide (50 mg daily). G-CSF and platelet transfusion support is permitted if needed.

Dose reduction for hematologic toxicity will begin with cyclophosphamide and then subsequently alternate with pomalidomide until a subject cannot tolerate dose level -2 of both agents - in which case subject would come off study. If subject has 2 or more concurrent toxicities that are potentially attributable to both agents (e.g. hematologic toxicity) then dose modification guidelines will be followed with dose reduction being done sequentially with one agent at a time, unless in the opinion of the investigator, both agents required concurrent dose reduction.

Study Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Pomalidomide, Daily Low Dose Oral Cyclophosphamide, and Dexamethasone in Relapsed/Refractory Multiple Myeloma

Study Start Date :

Jun 1, 2014

Actual Primary Completion Date :

May 7, 2019

Actual Study Completion Date :

May 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pomalidomide, Cyclophosphamide, Dexamethasone Three oral drugs will be given in 28-day cycles: Pomalidomide 4 mg daily x 21 days; cyclophosphamide 50 mg BID x 21 days; and dexamethasone 40 mg weekly x 3 (20 mg weekly if the patient aged ≥ 75 years old)	Drug: Pomalidomide 4 mg PO x 21 days Other Names: pomalyst Drug: Cyclophosphamide low dose cyclophosphamide 50 mg PO BID x 21 days Other Names: cytoxan Drug: Dexamethasone dexamethasone 40 mg PO weekly (or 20 mg if ≥ 75 years old).

Arm

Intervention/Treatment

Experimental: Pomalidomide, Cyclophosphamide, Dexamethasone

Three oral drugs will be given in 28-day cycles: Pomalidomide 4 mg daily x 21 days; cyclophosphamide 50 mg BID x 21 days; and dexamethasone 40 mg weekly x 3 (20 mg weekly if the patient aged ≥ 75 years old)

Drug: Pomalidomide

4 mg PO x 21 days

Other Names:

pomalyst

Drug: Cyclophosphamide

low dose cyclophosphamide 50 mg PO BID x 21 days

Other Names:

cytoxan

Drug: Dexamethasone

dexamethasone 40 mg PO weekly (or 20 mg if ≥ 75 years old).

Outcome Measures

Primary Outcome Measures

Best overall response rate (ORR) [up to 24 months]
disease response

Secondary Outcome Measures

Stringent complete response (sCR) [up to 24 months]
Complete response (CR) [up to 24 months]
Very good partial response (VGPR) [up to 24 months]
Partial response (PR) [up to 24 months]
Time to progression (TTP) [up to 24 months]
TTP is defined as beginning with the time the first dose of PCD regimen is administered until disease progression on PCD regimen.
Duration of response (DOR) [up to 24 months]
DOR is defined as the time from first evidence of PR or better to confirmation of disease progression.
Clinical benefit response (CBR) [up to 24 months]
CBR is the combination of the ORR and minimal response (MR) i.e. this includes sCR, CR, VGPR, PR, and MR.
Progression free survival (PFS) [up to 24 months]
PFS is defined as the duration of time from start of treatment to the first occurrence of disease progression or death on study from any cause, whichever occurs earlier.
Overall survival (OS) [up to 24 months]
OS is defined as the time from the first dose of study treatment to the date of death (whatever the cause).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Disease related:

Patients must have a history of symptomatic multiple myeloma according to the IMWG criteria
Patients must have received at least two prior lines of therapy and also must be refractory to lenalidomide.
Patient has relapsed or relapsed/refractory MM.
Patients must currently have measurable disease, as defined as:

Serum M-protein ≥ 0.5 g/dL
Urine M-protein ≥ 200 mg/24 hours
Serum free light chain assay: involved FLC level ≥ 10 mg/dl provided serum FLC ratio is abnormal
If no monoclonal protein is detected, then > 30% monoclonal bone marrow plasma cells

Demographic:

Male or female adults ≥ 18 years old
Able to sign informed consent and to comply with the protocol
Life expectancy > 12 weeks
ECOG performance status ≤ 2
All study participants must be registered into the mandatory POMALYST REMS program, and be willing and able to comply with the requirements of the POMALYST REMS program.

Laboratory

ANC ≥ 1000/µL
Platelets ≥ 50,000/µL (Patients with plasma cells 50% of bone marrow nucleated cells, and platelets ≥ 30,000/µL will be permitted regardless of the baseline ANC)
Cr < 3
AST ≤ 2.5 x ULN
ALT ≤ 2.5 x ULN
Serum Bilirubin ≤ 1.5 x ULN (except patients with Gilbert's syndrome who must have a total bilirubin of <3 time ULN)

Other

Females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control at least 28 days before taking pomalidomide.

Exclusion Criteria:

Previous treatment with pomalidomide
Patients who received chemotherapy or radiation therapy to 30% of marrow-bearing bone within ≤ 2 weeks or experimental agent/therapy within 4 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies
Known hypersensitivity to thalidomide or lenalidomide
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide or similar drugs
Other concurrent severe and/or uncontrolled medical conditions including abnormal laboratory values that could cause unacceptable safety risks or compromise compliance with the protocol
Patients for whom prophylactic anticoagulation therapy is not an option unless due to thrombocytopenia
Patients who received allogenic stem cell transplantation < 12 months prior to entering the study or show evidence of active graft-versus-host disease that requires immunosuppressive therapy
Patients with existing peripheral neuropathy grade > 2
Patients with an active malignancy requiring treatment in the next 12 months (except for basal or squamous cell carcinoma, or in situ cancer of the cervix or breast, and asymptomatic prostate cancer)
Patients with known positivity for HIV or active hepatitis B or C
Corticosteroid therapies of > 20 mg/day prednisone, > 4 mg/day dexamethasone, > 80 mg/day hydrocortisone, or equivalent. Oral, inhaled, or topical steroids are allowed during study as long as it does not exceed 80 mg/day hydrocortisone.