Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes

NCT00352001 | Completed Phase 1 Results DMC

• 5 other identifiers: CASE17Z05P30CA016042UCLA-0511032-01UCLA-RDN-5405UCLA-05011032-01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

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.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

refractory anemia with excess blasts; previously treated myelodysplastic syndromes; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes

Outcome Measures

Primary Outcomes (4)

• PHASE I: Maximum Tolerated Dose of Azacitidine

  Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.

  After 1 courses (1 months)

• PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)

  For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement. Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones. Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality. Hematologic Improvement (HI) is defined as: red blood cell increase of \>=1.5g/dL, a platelet response of \>=30X10\^9/L or by at least 100% for values starting \<20X10\^9/L, or a neutrophil response of at least 100% and absolute increase of \>0.5X10\^9/L

  After 4 courses (4 months)

• PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)

  For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement) Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones. Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality. Hematologic Improvement (HI) is defined as: red blood cell increase of \>=1.5g/dL, a platelet response of \>=30X10\^9/L or by at least 100% for values starting \<20X10\^9/L, or a neutrophil response of at least 100% and absolute increase of \>0.5X10\^9/L

  After 7 courses (months)

• PHASE I: Maximum Tolerated Dose of Lenalidomide

  Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.

  After 1 courses (1 months)

Secondary Outcomes (4)

• Time to Transformation to Acute Myeloid Leukemia or Death

  After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months

• Time to Relapse After Achieving Complete Response

  After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months

• Number of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events

  After 7 months

• Overall Survival Among Patients With Complete Response

  After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months

Study Arms (1)

Lenalidomide and Azacitidine

EXPERIMENTAL

Drug: azacitidine; Drug: lenalidomide

Interventions

azacitidine 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.

Also known as: Vidaza®

Lenalidomide and Azacitidine

lenalidomide 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.

Also known as: Revlimid®

Lenalidomide and Azacitidine

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of myelodysplastic syndromes (MDS) meeting one of the following criteria: * French-American-British histological classification criteria * Refractory anemia with excess blasts (RAEB), defined as 5-19% myeloblasts in the bone marrow * Patients with 20% blasts are considered to have acute myeloid leukemia (per WHO classification system) and are therefore excluded in this study * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mikkael Sekeres MD: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

University of California at Los Angeles

Los Angeles, California, 90095-1781, United States

Location

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

Tampa, Florida, 33612-9497, United States

Location

Cleveland Clinic Taussig Cancer Instititute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• 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.

  PMID: 22915641 DERIVED

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Leukemia, Myelomonocytic, Chronic

Interventions

Azacitidine; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Anemia, Refractory; Anemia; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Mikkael Sekeres
• Organization: CCCC

sekerem@ccf.org

216-445-9353

Study Officials

• Mikkael A. Sekeres, MD, MS

  The Cleveland Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 13, 2006
• First Posted: July 14, 2006
• Study Start: May 1, 2006
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: September 19, 2018
• Results First Posted: September 19, 2018

Record last verified: 2018-09

Locations

US (3)