Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
Trial record 42 of 52 for:    LENALIDOMIDE AND Leukemia AND Acute Myeloid Leukemia (AML)

Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00352001
Recruitment Status : Completed
First Posted : July 14, 2006
Results First Posted : September 19, 2018
Last Update Posted : September 19, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mikkael Sekeres MD, Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE July 13, 2006
First Posted Date  ICMJE July 14, 2006
Results First Submitted Date  ICMJE April 10, 2014
Results First Posted Date  ICMJE September 19, 2018
Last Update Posted Date September 19, 2018
Study Start Date  ICMJE May 2006
Actual Primary Completion Date September 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2018)
  • PHASE I: Maximum Tolerated Dose of Azacitidine [ Time Frame: After 1 courses (1 months) ]
    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.
  • PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate) [ Time Frame: After 4 courses (4 months) ]
    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
  • PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate) [ Time Frame: After 7 courses (months) ]
    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
  • PHASE I: Maximum Tolerated Dose of Lenalidomide [ Time Frame: After 1 courses (1 months) ]
    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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00352001 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2018)
  • Time to Transformation to Acute Myeloid Leukemia or Death [ Time Frame: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months ]
    Time (in months) patients took to evolve to myeloid leukemia or death after achieving a complete response using the RECIST criteria
  • Time to Relapse After Achieving Complete Response [ Time Frame: 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 [ Time Frame: After 7 months ]
  • Overall Survival Among Patients With Complete Response [ Time Frame: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months ]
    Time (in months) patients who achieved a complete response using the RECIST criteria were alive on study
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes
Official Title  ICMJE A Phase I/II Study of Revlimid (Lenalidomide) in Combination With Vidaza (Azacitidine) in Patients With Advanced Myelodysplastic Syndrome (MDS)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Myelodysplastic Syndromes
Intervention  ICMJE
  • Drug: 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.
    Other Name: Vidaza®
  • 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.
    Other Name: Revlimid®
Study Arms  ICMJE Experimental: Lenalidomide and Azacitidine
Interventions:
  • Drug: azacitidine
  • Drug: lenalidomide
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 18, 2018)
37
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE September 2011
Actual Primary Completion Date September 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00352001
Other Study ID Numbers  ICMJE CASE17Z05
P30CA016042 ( U.S. NIH Grant/Contract )
UCLA-0511032-01
UCLA-RDN-5405
UCLA-05011032-01
CASE17Z05 ( Other Identifier: Case Comprehensive Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mikkael Sekeres MD, Case Comprehensive Cancer Center
Study Sponsor  ICMJE Mikkael Sekeres MD
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Mikkael A. Sekeres, MD, MS The Cleveland Clinic
PRS Account Case Comprehensive Cancer Center
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP