Clinical trial NCT00463385: A Phase II Study of Pomalidomide in Myelofibrosis With Myeloid Metaplasia
Official title: A Phase 2, Prospective, Randomized, Multicenter, Double-blind, Active-control, Parallel-group Study to Determine the Safety of and to Select a Treatment Regimen of CC-4047 (Pomalidomide) Either as Single-agent or in Combination With Prednisone to Study Further in Subjects With Myelofibrosis With Myeloid Metaplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2007-04-20
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment
timeFrame: Up to 168 days
Secondary outcomes:
measure: Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment
timeFrame: Up to 336 days
measure: Time to the First Clinical Response
timeFrame: Up to 168 days
measure: Duration of First Clinical Response
timeFrame: Up to 40 months
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores
timeFrame: Baseline and Cycle 6 (168 days).
measure: Change From Baseline in Hemoglobin Concentration for Responders
timeFrame: Baseline, Cycle 6 (168 days)
measure: Change From Baseline in Hemoglobin Concentration for Non-Responders
timeFrame: Baseline, Cycle 6 (168 days)
measure: Change From Baseline in Likert Abdominal Pain Scale
timeFrame: Baseline and Cycle 6 (168 days)
measure: Percentage of Participants With Clinical Response by Baseline JAK2 Assessment
timeFrame: Up to 336 days
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months).
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA School of Medicine Hematology/Oncology
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian HospitalWeill Medical College of Cornell University
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center Leukemia Department
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Internal Medicine, Hematology
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Pavia
country: Italy
facility: IRCCS Policlinico S. Matteo
city: Barcelona
country: Spain
facility: Hematology DepartmentHospital Clinic
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Trust
Study officials:
affiliation: Celgene Corporation
name: Robert Peter Gale, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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)