Pomalidomide for Chronic Graft-versus-Host Disease

Phase 2

Completed

Conditions: Graft vs Host Disease
Graft-Versus-Host Disease

Interventions: Drug: Pomalidomide

Registration Number: NCT01688466

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

- Pomalidomide is a drug that alters the body's immune response. It may help people who have chronic graft-versus-host disease (GvHD). GvHD may appear after a stem cell transplant, when immune cells in the transplant try to attack tissues in the person who received the transplant. GvHD is not easy to treat, and often does not respond to standard treatments. Researchers want to see if pomalidomide is a safe and effective treatment for GvHD.

Objectives:

- To test the safety and effectiveness of pomalidomide for GvHD that has not responded to standard treatments.

Eligibility:

- Individuals at least 18 years of age who have GvHD that has not responded to standard treatments.

Design:

* Participants will be screened with a physical exam and medical history. Blood and urine samples will also be collected. A lung function test and imaging studies will also be given.

* Participants will take pomalidomide capsules once a day for 4-week periods called cycles.

* Treatment will be monitored with frequent blood tests and imaging studies. Saliva samples and skin and mouth tissue biopsies will also be collected during treatment.

* Treatment will continue for six cycles (6 months), unless the GvHD gets worse or side effects are too severe. If the GvHD has improved at the end of the six cycles, participants may be able to continue to take pomalidomide for up to six more cycles.

Detailed Description: BACKGROUND:

* Chronic graft-versus-host disease (cGvHD) is the leading cause of non-relapse morbidity and mortality in persons after allogeneic hematopoietic cell transplants.

* About 50% of persons with cGvHD have disease refractory to systemic corticosteroids and there is no standard second-line therapy.

* Thalidomide, a drug with immune-modulating effects, was active in advanced cGvHD but was difficult to use at appropriate doses.

* Pomalidomide is related to thalidomide but with higher potency and more favorable toxicity profile. It is active in multiple myeloma and myeloproliferative neoplasm associated myelofibrosis. Preliminary data in humans with cGvHD are encouraging but data are limited.

OBJECTIVES:

- Primary: Determine whether pomalidomide is effective in persons with moderate or severe cGvHD not controlled by corticosteroids.

ELIGIBILITY:

Inclusion Criteria

* Moderate or severe cGvHD per National Institutes of Health (NIH) criteria

* Age 18 to 75 years old

* Karnofsky performance score greater than or equal to 60%

* Has cGvHD that did not respond to high-dose corticosteroids (average 0.5 mg/kg/d prednisone for greater than or equal to 8 weeks) or second-line therapy

* Receiving stable or tapering doses of systemic therapy in the preceding 4 weeks

* Agree to adhere to methods of contraception and other fertility control measures as prescribed by the protocol

Exclusion Criteria

* Acute GvHD (classic and late per NIH criteria)

* Absolute neutrophils \<1.0x10(9)/L, platelets \<75x10(9)/L, estimated creatinine clearance \<50 mL/min/1.73m(2)

* NIH lung score 3

* Pregnant or lactating

* Uncontrolled infection

DESIGN:

Randomized phase 2 trial with the single stage selection design. Patients will receive either a constant low dose of pomalidomide (0.5 mg/day) for six months or a strategy of increasing dose of pomalidomide from 0.5 mg/d up through each individual patient's maximum tolerated dose, with escalations by 0.5 mg/d every 2 weeks to a maximum of 2.0 mg/d. As an early stopping rule for futility, if after 7 patients have enrolled on either arm, 0 have responded, then no further patients will be accrued to that arm as soon as this can be determined. To protect patient safety, an early stopping rule will be implemented. With two arms, each of which has a maximal accrual of 16 patients, up to 32 evaluable patients will be randomized. Response assessments will occur every 3 months with primary efficacy endpoint evaluated at 6 months. Patients with responding disease will continue therapy for another 6 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
0.5 mg/day with Dose Escalation	Pomalidomide	0.5 mg/day with Dose Escalation by 0.5 mg/day increments every 2 weeks to a maximum of 2.0 mg/day
0.5 mg/day without Dose Escalation	Pomalidomide	0.5 mg/day without Dose Escalation

Primary Outcome Measures

Name	Time	Method
Overall Response at 6 Months	6 months	Overall response was assessed by the National Institutes of Health (NIH) Chronic Graft-Versus Host Disease (cGVHD) Response criteria. Complete response (CR) is complete resolution in all signs and symptoms at all affected organs or tissues. Partial response (PR) is improvement in ≥ 1 organ or tissue with no progression in any other affected organ or tissue. Response \< PR is a change towards improvement from the pre-treatment baseline but not meeting the criteria for CR or PR. Stable disease (SD) is no change in cGVHD. Flare is exacerbation of cGVHD manifestations during withdrawal of immunosuppressive therapy which do not exceed those at the beginning of the trial and improves after reinstatement of previous treatment. Progressive disease (PD) is failure of therapy to control cGVHD . Mixed response (improvement in some organs but worsening in others) will be categorized as progressive disease.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v4.0	50 months and 20 days	Here is the count of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v4.0. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.