A Phase II Study of Pomalidomide in Myelofibrosis With Myeloid Metaplasia

NCT00463385 | Completed Phase 2 Results DMC

• 1 other identifier: CC-4047-MMM-001
• Study Type: interventional
• Target: 88
• Locations: 5 countries
• Sites: 11

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).

Conditions

Myelofibrosis With Myeloid Metaplasia; Myeloid Metaplasia; Myelofibrosis

Keywords

Celgene; CC-4047; Myelofibrosis; myelofibrosis with myeloid metaplasia; myeloid metaplasia; JAK2; CC-4047-MMM-001; Prednisone; Phase II; pomalidomide; bone marrow histology; imids; MMM; Ashkenazi Jewish Population; exposure to Thorotrast; exposure to solvents (benzene and toluene); acute megakaryocytic leukemia; history of polycythemia vera

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment

  A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or 3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at \> 5 cm and became not palpable. Participants who discontinued the study early without achieving clinical response were counted as non-responders.

  Up to 168 days

Secondary Outcomes (9)

• Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment

  Up to 336 days

• Time to the First Clinical Response

  Up to 168 days

• Duration of First Clinical Response

  Up to 40 months

• Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores

  Baseline and Cycle 6 (168 days).

• Change From Baseline in Hemoglobin Concentration for Responders

  Baseline, Cycle 6 (168 days)

Study Arms (4)

Prednisone

EXPERIMENTAL

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.

Drug: Prednisone; Drug: Placebo to pomalidomide

Pomalidomide

EXPERIMENTAL

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.

Drug: Pomalidomide; Drug: Placebo to prednisone

Pomalidomide 2 mg + Prednisone

EXPERIMENTAL

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.

Drug: Pomalidomide; Drug: Prednisone

Pomalidomide 0.5 mg + Prednisone

EXPERIMENTAL

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.

Drug: Pomalidomide; Drug: Prednisone

Interventions

Pomalidomide DRUG

Also known as: CC-4047, Pomalyst

Pomalidomide; Pomalidomide 0.5 mg + Prednisone; Pomalidomide 2 mg + Prednisone

Prednisone 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; Pomalidomide 2 mg + Prednisone; Prednisone

Placebo to pomalidomide DRUG

Matching pomalidomide placebo tablets

Prednisone

Placebo to prednisone DRUG

Matching prednisone placebo tablets

Pomalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (11)

UCLA School of Medicine Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021-6007, United States

Location

New York Presbyterian HospitalWeill Medical College of Cornell University

New York, New York, 10021, United States

Location

MD Anderson Cancer Center Leukemia Department

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-4417, United States

Location

Medical University of Vienna, Department of Internal Medicine, Hematology

Vienna, A-1090, Austria

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

IRCCS Policlinico S. Matteo

Pavia, 27100, Italy

Location

Hematology DepartmentHospital Clinic

Barcelona, 08036, Spain

Location

Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Trust

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• 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)

  BACKGROUND

MeSH Terms

Conditions

Primary Myelofibrosis; Leukemia, Megakaryoblastic, Acute

Interventions

pomalidomide; Prednisone

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Robert Peter Gale, MD, PhD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2007
• First Posted: April 20, 2007
• Study Start: April 1, 2007
• Primary Completion: May 1, 2009
• Study Completion: December 31, 2013
• Last Updated: November 20, 2019
• Results First Posted: October 28, 2013

Record last verified: 2019-11

Locations

ES (1); AU (1); IT (2); GB (1); US (6)