Lenalidomide and Prednisone in Treating Patients With Myelofibrosis

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00227591
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Arm: 1
• Duration (Months): 60
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Essential Thrombocythemia; Polycythemia Vera; Primary Myelofibrosis	Drug: lenalidomide; Drug: prednisone; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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 Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [Assessed at the end of cycle 3]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Eastern Cooperative Oncology Group	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ayalew Tefferi, Eastern Cooperative Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00227591
• Other Study ID Numbers: NCI-2012-02976; NCI-2012-02976; ECOG-E4903; E4903; E4903; U10CA021115
• First Posted: Sep 28, 2005
• Last Update Posted: May 21, 2014
• Last Verified: Dec 1, 2012

• Additional relevant MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential; Prednisone; Lenalidomide

Study Results

Participant Flow

Recruitment Details	This study accrued 48 cases between December 2, 2005 and March 9, 2007. Per two-stage design, the study was suspended on May 31, 2006 for a toxicity and response analysis. Since more than 4 patients achieved a response, the study was reactivated on December 5, 2006. Accrual continued to a total of 48 patients and terminated on March 9, 2007.

Arm/Group Title	Lenalidomide
Arm/Group Description	Lenalidomide 10 mg/day plus prednisone X 28 days X 3 cycles
Period Title: Overall Study
STARTED	48
Began Treatment	47
COMPLETED	47
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Lenalidomide
Arm/Group Description	Lenalidomide 10 mg/day plus prednisone X 28 days X 3 cycles
Overall Participants	47
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	25 53.2%
>=65 years	22 46.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (11.2)
Sex: Female, Male (Count of Participants)
Female	21 44.7%
Male	26 55.3%
Region of Enrollment (participants) [Number]
United States	47 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

6 ineligible patients were excluded from the analysis.

Arm/Group Title	Lenalidomide
Arm/Group Description	Lenalidomide 10 mg/day plus prednisone X 28 days X 3 cycles
Measure Participants	42
Number (95% Confidence Interval) [Proportion of participants]	0.26 0.6%

Adverse Events

Time Frame	During treatment (up to 6 months) and for 30 days after the end of treatment.
Arm/Group Title	Lenalidomide
Arm/Group Description	Lenalidomide 10 mg/day plus prednisone X 28 days X 3 cycles
All Cause Mortality
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	47/47 (100%)
Blood and lymphatic system disorders
Anemia	21/47 (44.7%)
Leukopenia	14/47 (29.8%)
Lymphopenia	1/47 (2.1%)
Neutropenia	21/47 (44.7%)
Thrombocytopenia	9/47 (19.1%)
Cardiac disorders
Atrial fibrillation	1/47 (2.1%)
Heart block sick sinus syndrome	1/47 (2.1%)
Pericardial effusion	1/47 (2.1%)
Pulmonary hypertension	1/47 (2.1%)
Gastrointestinal disorders
Abdomen pain	1/47 (2.1%)
Diarrhea without prior colostomy	1/47 (2.1%)
General disorders
Dizziness	1/47 (2.1%)
Fatigue	3/47 (6.4%)
Pain NOS	1/47 (2.1%)
Infections and infestations
Infection with gr3-4 neutrophils	1/47 (2.1%)
Metabolism and nutrition disorders
ALT Increased	1/47 (2.1%)
Alkaline Phosphatase Increased	1/47 (2.1%)
Bilirubin Increased	2/47 (4.3%)
Hyperglycemia	2/47 (4.3%)
Hyperkalemia	1/47 (2.1%)
Hyperuricemia	1/47 (2.1%)
Musculoskeletal and connective tissue disorders
Back pain	1/47 (2.1%)
Soft tissue necrosis	1/47 (2.1%)
Nervous system disorders
Syncope	1/47 (2.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/47 (2.1%)
Vascular disorders
Edema limb	1/47 (2.1%)
Thrombosis	2/47 (4.3%)
Other (Not Including Serious) Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	47/47 (100%)
Blood and lymphatic system disorders
Anemia	43/47 (91.5%)
Leukopenia	29/47 (61.7%)
Neutropenia	22/47 (46.8%)
Thrombocytopenia	27/47 (57.4%)
Gastrointestinal disorders
Constipation	10/47 (21.3%)
Diarrhea witout prior colostomy	21/47 (44.7%)
Dyspepsia muco	8/47 (17%)
General disorders
Dizziness	9/47 (19.1%)
Fatigue	19/47 (40.4%)
Headache	6/47 (12.8%)
Insomnia	8/47 (17%)
Pain NOS	6/47 (12.8%)
Sweating	6/47 (12.8%)
Taste disturbance	6/47 (12.8%)
Weight loss	7/47 (14.9%)
Metabolism and nutrition disorders
AST increased	8/47 (17%)
Anorexia	6/47 (12.8%)
Bilirubin Increased	8/47 (17%)
Hyperglycemia	13/47 (27.7%)
Hypokalemia	8/47 (17%)
Musculoskeletal and connective tissue disorders
Extremity limb pain	7/47 (14.9%)
Skin and subcutaneous tissue disorders
Pruritus	5/47 (10.6%)
Rash	9/47 (19.1%)
Vascular disorders
Edema limb	15/47 (31.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.