CC-4047 (Pomalidomide) for Graft vs. Host Disease

Phase 2

Completed

Brief Summary: This study will test the safety and effectiveness CC-4047 (pomalidomide) in patients with advanced, steroid refractory graft-versus-host disease.

Detailed Description: Chronic Graft vs. Host Disease is a major complication after allogeneic hematopoietic stem cell transplantation developing in 30 - 70% of patients. It is a multisystem alloimmune and autoimmune disorder with a negative impact on quality of life and functional status, increased need for extended immunosuppression and is the leading cause of late transplant related mortality.

CC-4047 is a novel immune modulatory drug that is a thalidomide analog with a 4,000 fold greater inhibition of TNF-α production related to thalidomide. Several features of CC-4047 suggest that this drug may be useful in treating chronic GVHD including in vitro suppression of TNF-α production, increasing Th1 and stimulation of IL-12 and sIL-Rα.

This study is an open-label, single-arm, pilot study of efficacy and safety of CC-4047 in patients with advanced chronic GvHD who failed to achieve a response with high-dose corticosteroids or second line systemic immunosuppressive therapy.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Pregnant or lactating females.
New immunosuppressive therapy started within the preceding 4 weeks.
Extracorporeal photopheresis within the preceding 3 months.
Hypersensitivity to any immune modulator drug (IMiD™).
Unable to take prophylactic anticoagulation.
Any condition which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
Acute, persistent, recurrent or late-onset acute GvHD defined by NIH criteria.
Any of the following laboratory values at registration:
- absolute neutrophil count (ANC) less than 1.0 x 109/L,
- platelets less than 75 x 109/L, or
- creatinine clearance less than 50 mL/min (Cockroft-Gault formula).
Uncontrolled infection requiring systemic antibiotics.
Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection.
Known uncontrolled arrhythmias or symptomatic heart disease or left ventricular ejection fraction less than 40% (an ECHO should be performed as clinically indicated)
Recurrence of cancer for which the transplant was done except for presence of minimal residual disease by PCR.
Other cancer less than or equal to 2 years prior study-entry except:
Basal cell carcinoma of the skin,
Squamous cell carcinoma of the skin,
Carcinoma in situ of the cervix,
Carcinoma in situ of the breast, or
Prostate cancer (Tumor, Node, Metastasis [TNM] stage T1a or T1b)

Arm && Interventions

Group	Intervention	Description
CC-4047 Arm	CC-4047	CC-4047 2 mg orally every day for 1 course (12 weeks or 84 days). Every 28 days of treatment are considered as 1 cycle and every 3 cycles are are considered as 1 course of treatment. A total of 4 courses of treatment are planned (12 months).

Primary Outcome Measures

Name	Time	Method
Overall Response (Complete Response + Partial Response + Other)	1 year after last dose of CC-4047	* CR is defined as complete resolution in all of signs and symptoms at all affected organs and tissues * PR is defined as improvement in greater than or equal to 1 organ/tissue with no progression in any other affected organ/tissue * Improvement in chronic GvHD symptoms less than what meets the definition of a PR is defined as other * Progressive disease is defined as failure of therapy to control chronic GvHD despite increasing the dose of primary therapy or adding second line treatments * No response is defined as no change in disease.

Secondary Outcome Measures

Name	Time	Method
Safety as Measured by the Most Common Adverse Effects and Reasons for Dose Reductions or Study-discontinuation	30 days after last dose of CC-4047 or until resolution of event	-Toxicities will be graded according to the NCI CTCAE v3.0.