Lenalidomide and Prednisone in Treating Patients With Myelofibrosis

A Phase II Study of Lenalidomide (CC-5013) in Combination With Prednisone for the Treatment of Myelofibrosis With Myeloid Metaplasia

This phase II trial is studying how well giving lenalidomide together with prednisone works in treating patients with myelofibrosis. Lenalidomide may stop the growth of myelofibrosis by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with prednisone may kill more cancer cells.

Study Overview

• Status: Completed
• Conditions: Primary Myelofibrosis; Polycythemia Vera; Essential Thrombocythemia
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: lenalidomide; Drug: prednisone

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the rate of complete or partial remission from treatment with a combination of lenalidomide and prednisone in patients with myelofibrosis with myeloid metaplasia.

SECONDARY OBJECTIVES:

I. To examine drug toxicity. II. To examine duration of response. III. To examine the effect of treatment on bone marrow fibrosis, angiogenesis, and cytogenetics.

OUTLINE:

For courses 1 and 2, patients receive oral lenalidomide once daily and oral prednisone once daily on days 1-28. For course 3, patients receive oral lenalidomide once daily on days 1-28 and oral prednisone once on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, and 27. Patients with stable or responding disease after course 3 receive oral lenalidomide alone once daily on days 1-28 for courses 4-6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for up to 5 years from study entry.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Eastern Cooperative Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient must be diagnosed with myelofibrosis with myeloid metaplasia (MMM); agnogenic myeloid metaplasia, post-polycythemic myeloid metaplasia, or post-thrombocythemic myeloid metaplasia are included

  • NOTE: Diagnosis must be confirmed by central pathology review; diagnostic samples must be submitted; patient may register and begin treatment based on the local pathology review. If the central review does not confirm patient's eligibility to participate in the trial, protocol treatment must be discontinued

• Patient must have discontinued chemotherapy (hydroxyurea, alpha interferon, anagrelide, other myelosuppressive agents, thalidomide, or any other experimental therapy) as well as growth factors and systemic use of corticosteroids >= 28 days prior to starting study drug

  • All non-hematologic toxicity must be resolved to =< grade 1
• Patient must be lenalidomide-naïve (never treated with lenalidomide)
• ECOG performance status (PS) of 0, 1, or 2 at study entry
• Hemoglobin level =< 10 g/dL or transfusion-dependent
• Absolute neutrophil count >= 1,000 uL
• Platelet count >= 100,000 uL
• Serum creatinine =< 2.0 mg/dL
• Total bilirubin =< 2.0 mg/dL (if elevated; direct bilirubin =< 2.0 mg/dL)
• AST (SGOT) =< 3 x ULN unless attributed to hepatic extramedullary hematopoiesis

• Women must not be pregnant or breastfeeding because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenetic effects on the developing fetus and newborn are unknown; women of childbearing potential who are sexually active, must use 2 accepted methods of birth control at the same time for 4 weeks prior to lenalidomide treatment, during lenalidomide treatment, and up to 4 weeks after lenalidomide treatment is finished; sexually active males must use a latex condom for contraception during the study and up to 4 weeks after treatment with lenalidomide has ended

  • All females of childbearing potential must have a blood test 10-14 days prior to the start of lenalidomide treatment to rule out pregnancy; another blood test to rule out pregnancy must be done 24 hours prior to the start of treatment with lenalidomide
• Patient must not have any condition, including the presence of laboratory abnormalities, which, based on the physician's opinion, places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Patient must not have any known hypersensitivity to thalidomide or lenalidomide
• Patient must not have any known positive status for HIV or infectious hepatitis type A, B or C

• Patient must not have any other active malignancy

  • NOTE: SWOG patients are strongly encouraged to be registered on SWOG-9007 ("Cytogenetic Studies in Leukemia Patients"); SWOG institutions registering patients to SWOG-9007 should follow the instructions for specimen submission

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (lenalidomide, prednisone); For courses 1 and 2, patients receive oral lenalidomide once daily and oral prednisone once daily on days 1-28. For course 3, patients receive oral lenalidomide once daily on days 1-28 and oral prednisone once on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, and 27. Patients with stable or responding disease after course 3 receive oral lenalidomide alone once daily on days 1-28 for courses 4-6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Other: laboratory biomarker analysis; Correlative studies; Drug: lenalidomide; Given orally (PO); Other Names: CC-5013; IMiD-1; Revlimid; Drug: prednisone; Given PO; Other Names: DeCortin; Deltra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	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.	Assessed at the end of cycle 3

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ayalew Tefferi, Eastern Cooperative Oncology Group

Publications and helpful links

General Publications

• Mesa RA, Yao X, Cripe LD, Li CY, Litzow M, Paietta E, Rowe JM, Tefferi A, Tallman MS. Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903. Blood. 2010 Nov 25;116(22):4436-8. doi: 10.1182/blood-2010-05-287417. Epub 2010 Jul 22.

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: September 26, 2005
• First Submitted That Met QC Criteria: September 26, 2005
• First Posted (Estimate): September 28, 2005

Study Record Updates

• Last Update Posted (Estimate): May 21, 2014
• Last Update Submitted That Met QC Criteria: May 2, 2014
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Primary Myelofibrosis; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Prednisone
• Other Study ID Numbers: NCI-2012-02976 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA021115 (U.S. NIH Grant/Contract); ECOG-E4903; E4903 (Other Identifier: CTEP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No