A Phase II Study of Pomalidomide in Myelofibrosis With Myeloid Metaplasia

NCT ID: NCT00463385

Last Updated: 2019-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-01
• Study Completion Date: 2013-12-31

Brief Summary

The purpose of this study is to determine the safety of and to select a treatment regimen of pomalidomide (CC-4047) either as single-agent or in combination with prednisone to study further in patients with myelofibrosis with myeloid metaplasia (MMM).

Detailed Description

Participants received study treatment in the Double Blind Treatment Phase for up to 12 cycles (336 days; 12 cycles of 28 days each). Participants who completed the Double-Blind Treatment Phase were unblinded and, if receiving pomalidomide and determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, could have continued on their current dose of pomalidomide until disease progression. Participants receiving placebo were discontinued from the study.

Conditions

Myelofibrosis With Myeloid Metaplasia; Myeloid Metaplasia; Myelofibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Prednisone

Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase.

After the completion of cycle 12 and upon unblinding, participants were discontinued from the study.

Group Type: EXPERIMENTAL

Prednisone

Intervention Type: DRUG

Participants will take oral prednisone in the evening for 3 cycles of 28 days each (up to 84 days). The dose will be as follows: 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day.

Placebo to pomalidomide

Intervention Type: DRUG

Matching pomalidomide placebo tablets

Pomalidomide

Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase.

After the completion of Cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.

Group Type: EXPERIMENTAL

Pomalidomide

Intervention Type: DRUG

Placebo to prednisone

Intervention Type: DRUG

Matching prednisone placebo tablets

Pomalidomide 2 mg + Prednisone

Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase.

After the completion of cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.

Group Type: EXPERIMENTAL

Pomalidomide

Intervention Type: DRUG

Prednisone

Intervention Type: DRUG

Participants will take oral prednisone in the evening for 3 cycles of 28 days each (up to 84 days). The dose will be as follows: 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day.

Pomalidomide 0.5 mg + Prednisone

Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase.

After the completion of cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.

Group Type: EXPERIMENTAL

Pomalidomide

Intervention Type: DRUG

Prednisone

Intervention Type: DRUG

Participants will take oral prednisone in the evening for 3 cycles of 28 days each (up to 84 days). The dose will be as follows: 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day.

Interventions

Pomalidomide

Intervention Type: DRUG

Prednisone

Participants will take oral prednisone in the evening for 3 cycles of 28 days each (up to 84 days). The dose will be as follows: 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day.

Intervention Type: DRUG

Placebo to pomalidomide

Matching pomalidomide placebo tablets

Intervention Type: DRUG

Placebo to prednisone

Matching prednisone placebo tablets

Intervention Type: DRUG

Other Intervention Names

CC-4047; Pomalyst

Eligibility Criteria

Inclusion Criteria

• Must sign an informed consent form
• Must be >18 years of age
• Must be diagnosed with myelofibrosis
• Eligibility is based on local pathology review of bone marrow aspirate and biopsy
• Screening total hemoglobin level < 10g/dL or transfusion-dependent anemia defined as per International Working Group (IWG) criteria.
• Must have adequate organ function as demonstrated by the following ≤ 14 days prior to starting study drug:

• Alanine aminotransferase (ALT; SGPT)/aspartate aminotransferase (AST; SGOT) ≤ 3 x upper limit of normal (ULN), [unless upon judgment of the treating physician, it is believed to be due to extra-medullary hematopoiesis (EMH)].
• Total Bilirubin <3x ULN or Direct Bilirubin <2 x ULN
• Serum creatinine ≤ 2.0 mg/dL
• Absolute neutrophil count ≥ 1,000/μL (≥ 1 x 10^9/L).
• Platelet count ≥ 50,000 /μL (≥ 50 x 10^9/L).
• Patients must be willing to receive transfusion of blood products
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at screening.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• No active malignancies with the exception of controlled prostate cancer, basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
• Must agree to follow pregnancy precautions as required per the protocol

Exclusion Criteria

• Known positive status for human immunodeficiency virus (HIV), hepatitis B carrier, or active hepatitis C infection.
• Previous untoward reaction to corticosteroid (specifically, prednisone) therapy that was severe enough, in the opinion of the treating physician, to preclude study participation.
• The use of any growth factors, cytotoxic chemotherapeutic agents (e.g. hydroxyurea and anagrelide), corticosteroids, or experimental drug or therapy within a minimum of 28 days of starting CC-4047 and/or lack of recovery from all toxicity from previous therapy to grade 1 or better (e.g. alpha interferon may require 84 days of longer or washout).
• Prior therapy with CC-4047 or, lenalidomide or thalidomide for Myelofibrosis with myeloid metaplasia (MMM). (Prior prednisone use as a therapy for MMM is allowed, but not within 28 days of starting CC-4047).
• History of deep vein thrombosis or pulmonary embolism within one year of starting study medication.
• Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Pregnant or lactating females

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Peter Gale, MD, PhD

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

UCLA School of Medicine Hematology/Oncology

Los Angeles, California, United States

Mayo Clinic

Rochester, Minnesota, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

New York Presbyterian HospitalWeill Medical College of Cornell University

New York, New York, United States

MD Anderson Cancer Center Leukemia Department

Houston, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Medical University of Vienna, Department of Internal Medicine, Hematology

Vienna, , Austria

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

IRCCS Policlinico S. Matteo

Pavia, , Italy

Hematology DepartmentHospital Clinic

Barcelona, , Spain

Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Trust

Sheffield, , United Kingdom

Countries

United States; Austria; Italy; Spain; United Kingdom

References

Barosi G, et al. Decrease Of T Regulatory Cells In Patients With Myelofibrosis Receiving Ruxolitinib. Presented at American Society of Hematology 2013, December 7-10, 2013, New Orleans, LA. Abstract No. 4057. Blood, 2013;122(21)

Reference Type: BACKGROUND

Other Identifiers

CC-4047-MMM-001

Identifier Type: -

Identifier Source: org_study_id