Lenalidomide and Prednisone in Treating Patients With Myelofibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00227591
First received: September 26, 2005
Last updated: July 23, 2013
Last verified: October 2012
  Purpose

Myelofibrosis with myeloid metaplasia (MMM) is a clonal hematopoietic stem cell disorder characterized by progressive anemia, marked splenomegaly, bone marrow collagen fibrosis, progression to acute leukemia, and premature death. MMM includes primary myelofibrosis and myelofibrosis from antecedent polycythemia vera or essential thrombocythemia. Anemia contributes to substantial symptoms of fatigue associated with myelofibrosis and is strongly correlated with shorter survival.

The pilot studies with thalidomide treatment both with and without prednisone tapers at the average dose of 200 mg/day have resulted in a clinically relevant improvement of anemia (20%), splenomegaly (23%), and thrombocytopenia (71%). However, a high incidence of adverse side effects including problematic neuropathy has motivated the investigation of a more potent thalidomide derivative with reduced toxicity.

Lenalidomide appears to have a similar range of activities as thalidomide with a better toxicity profile. In a large phase II trial with 68 subjects, lenalidomide administered at 10 mg/day resulted in overall response rates of 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. The promising results of the single agent activity of lenalidomide and the synergy between lenalidomide and corticosteroids has initiated the current phase II trial combining lenalidomide with a prednisone taper, which has been undertaken by the Eastern Cooperative Oncology Group (ECOG).

PURPOSE: This phase II trial is studying how well giving lenalidomide together with prednisone works in treating patients with myelofibrosis.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Drug: lenalidomide
Drug: prednisone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Lenalidomide (CC-5013) in Combination With Prednisone for the Treatment of Myelofibrosis With Myeloid Metaplasia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: Assessed at the end of cycle 3 ] [ Designated as safety issue: No ]

    Response was evaluated for Anemia and Spleen:

    Major anemia response: hemoglobin increase to within normal limits in the absence of transfusion. Minor anemia response: hemoglobin improvement of at least 2 grams per deciliter independent of transfusion support, or achievement of transfusion independence in transfusion-dependent patients. Major spleen response: normalization of spleen size to the range of 12-14 centimeters by ultrasound. Minor spleen response: a 50% or more decrease in excess spleen size by ultrasound. Complete remission (CR): complete resolution of disease-related symptoms, splenomegaly, normalization of peripheral blood count, white cell differential and smear, and normalization of bone marrow histology. Partial remission (PR): a major or minor response in anemia or splenomegaly. Overall Response (OR)=CR + PR, assessed among eligible, treated patients.



Enrollment: 48
Study Start Date: December 2005
Study Completion Date: March 2012
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide
Lenalidomide 10 mg/day plus prednisone X 28 days X 3 cycles
Drug: lenalidomide
10 mg/day plus prednisone X 28 days X 3 cycles
Other Name: CC-5013
Drug: prednisone
For the first month, prednisone 30 mg/day was administered orally and was decreased to 15 mg/day for the second month, and then to 15 mg every other day for the third month.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the rate of complete or partial remission in patients with myelofibrosis with myeloid metaplasia treated with lenalidomide and prednisone.

Secondary

  • Determine the toxic effects of this regimen in these patients.
  • Determine the duration of response in patients treated with this regimen.
  • Determine the effect of this regimen on bone marrow fibrosis, angiogenesis, and cytogenetics in these patients.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of MMM confirmed by central pathology review
  • Discontinued prior therapy for their disease including chemotherapy, growth factors, and systemic use of corticosteroids for at least 28 days prior to starting the study drug
  • ECOG performance status of 0-2
  • At least 18 years of age
  • Hemoglobin < 10 g/dl or transfusion-dependent, absolute neutrophil count ≥ 1,000 µL, platelet count ≥ 100,000 µL, serum creatinine ≤ 2.0 mg/dL, total bilirubin ≤ 2.0 mg/dL, aspartate aminotransferase (AST)≤ 3 ×Upper Limit of Normal (unless attributed to hepatic extramedullary hematopoiesis) within 2 weeks of registration
  • Negative pregnancy test
  • Written informed consent

Exclusion Criteria:

  • Treated with lenalidomide
  • Conditions that place the patient at unacceptable risk based on the physician's opinion including the presence of laboratory abnormalities
  • hypersensitivity to thalidomide or lenalidomide.
  • Positive status for HIV or infectious hepatitis type A, B, or C
  • Active malignancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00227591

  Show 90 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Ayalew Tefferi, MD Mayo Clinic
Study Chair: Larry D. Cripe, MD Indiana University Melvin and Bren Simon Cancer Center
  More Information

Additional Information:
No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00227591     History of Changes
Other Study ID Numbers: NCI-2012-02976, U10CA021115, E4903, CDR0000442403
Study First Received: September 26, 2005
Results First Received: October 11, 2012
Last Updated: July 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
chronic idiopathic myelofibrosis
polycythemia vera
essential thrombocythemia
lenalidomide
anemia

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Prednisone
Lenalidomide
Thalidomide
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014