Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes

NCT ID: NCT00352001

Last Updated: 2018-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2011-09-30

Brief Summary

RATIONALE: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Lenalidomide may also stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may also cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving lenalidomide together with azacitidine may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lenalidomide and azacitidine in treating patients with advanced myelodysplastic syndromes.

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and dose-limiting toxicity of lenalidomide and azacitidine in patients with advanced myelodysplastic syndromes (MDS).

Secondary

• Review clinical outcomes, as defined by the International Working Group criteria, in patients treated with this regimen.
• Determine time to transformation to acute myeloid leukemia or death in patients treated with this regimen.
• Determine time to relapse after achieving complete or partial remission in patients treated with this regimen.
• Determine time to disease progression in patients treated with this regimen.
• Determine the effect of this regimen on hematologic status (including peripheral blood counts and the need for platelet and/or red blood cell transfusions) in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study.

Patients receive oral lenalidomide once daily on days 1-14 or days 1-21 and azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses and/or increasing dosing frequencies of lenalidomide and azacitidine until the maximum tolerated dose (MTD) is determined or the sixth dose level is reached, whichever occurs first. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy.

After completion of study treatment, patients are followed annually.

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lenalidomide and Azacitidine

Group Type: EXPERIMENTAL

azacitidine

Intervention Type: DRUG

Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide

Intervention Type: DRUG

Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Interventions

azacitidine

Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Intervention Type: DRUG

lenalidomide

Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Intervention Type: DRUG

Other Intervention Names

Vidaza®; Revlimid®

Eligibility Criteria

Exclusion Criteria

• Chronic myelomonocytic leukemia (CMML), defined as 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood
• WHO histological classification criteria

• RAEB-1, defined as 5-9% myeloblasts in the bone marrow
• RAEB-2, defined as 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood
• CMML-2, defined as 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood
• International Prognostic Scoring System (IPSS) score of intermediate 2 (1.5-2.0 points based on karyotype, cytopenias, and bone marrow blast percentage) or high (≥ 2.5 points), in the setting of ≥ 5% myeloblasts
• Considered ineligible for bone marrow transplantation as first-line therapy

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 3 months
• ECOG performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method contraception for 4 weeks before, during, and for 4 weeks after completion of study treatment
• No serious medical condition, laboratory abnormality, or psychiatric illness that, in the opinion of the treating physician, would preclude study participation or preclude giving informed consent
• No preexisting neurotoxicity or neuropathy ≥ grade 2
• No rash or prior hypersensitivity or allergic reaction ≥ grade 3 to thalidomide
• Creatinine ≤ 2.0 mg/dL
• AST and ALT ≤ 2.0 times upper limit of normal
• Bilirubin ≤ 2 mg/dL
• Platelet count ≥ 50,000/mm^3
• Absolute neutrophil count ≥ 500/mm^3
• No other malignancy within the past 3 years except curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer
• No history of thromboembolic event or other condition requiring use of anticoagulation with warfarin or low molecular-weight heparin
• No known or suspected hypersensitivity to azacitidine or mannitol

PRIOR CONCURRENT THERAPY:

• More than 28 days since prior and no other concurrent investigational agents for MDS
• More than 28 days since prior approved therapy for MDS
• More than 14 days since prior growth factors
• More than 28 days since prior and no concurrent supraphysiologic doses (equivalent to > 10 mg/day of prednisone) of corticosteroids
• More than 12 months since prior radiotherapy, chemotherapy, or cytotoxic therapy for treatment of conditions other than MDS
• No prior lenalidomide or azacitidine
• No prior stem cell or bone marrow transplantation
• No concurrent androgens, epoetin alfa, or chemotherapy for MDS

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mikkael Sekeres MD

OTHER

Sponsor Role: lead

Responsible Party

Mikkael Sekeres MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mikkael A. Sekeres, MD, MS

Role: STUDY_CHAIR

The Cleveland Clinic

Locations

University of California at Los Angeles

Los Angeles, California, United States

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, United States

Cleveland Clinic Taussig Cancer Instititute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

References

Sekeres MA, Tiu RV, Komrokji R, Lancet J, Advani AS, Afable M, Englehaupt R, Juersivich J, Cuthbertson D, Paleveda J, Tabarroki A, Visconte V, Makishima H, Jerez A, Paquette R, List AF, Maciejewski JP. Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes. Blood. 2012 Dec 13;120(25):4945-51. doi: 10.1182/blood-2012-06-434639. Epub 2012 Aug 22.

Reference Type: DERIVED

PMID: 22915641 (View on PubMed)

Other Identifiers

P30CA016042

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UCLA-0511032-01

Identifier Type: -

Identifier Source: secondary_id

UCLA-RDN-5405

Identifier Type: -

Identifier Source: secondary_id

UCLA-05011032-01

Identifier Type: -

Identifier Source: secondary_id

CASE17Z05

Identifier Type: OTHER

Identifier Source: secondary_id

CASE17Z05

Identifier Type: -

Identifier Source: org_study_id

NCT00326846

Identifier Type: -

Identifier Source: nct_alias