Lenalidomide and Decitabine in High Grade Myelodysplastic Syndromes

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00828802
First received: January 22, 2009
Last updated: September 6, 2013
Last verified: September 2013

January 22, 2009
September 6, 2013
March 2009
August 2012   (final data collection date for primary outcome measure)
Maximally tolerated dose (MTD)as defined by the protocol [ Time Frame: Cycle 1 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00828802 on ClinicalTrials.gov Archive Site
  • response duration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • effect on cytogenetic abnormalities [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • response duration [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • effect on cytogenetic abnormalities [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Lenalidomide and Decitabine in High Grade Myelodysplastic Syndromes
A Phase I Study of Lenalidomide in Combination With Decitabine for Patients With High Grade Myelodysplastic Syndromes

The purpose of this study is to find out what dose of lenalidomide is safe to use in combination with decitabine when given in people with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a group of different kinds of stem cell abnormalities. It is characterized by low blood counts and abnormal blood cell formation. These abnormal blood cells can cause fatigue, shortness of breath, infection, and bleeding. There is significant risk of developing acute leukemia in this disorder.

The only known curative therapy is an allogeneic bone marrow transplant of which the vast majority of patients with this disorder are not candidates. Currently three drugs have been approved for the treatment of MDS: azacytidine, decitabine and lenalidomide for low grade patients with a chromosome 5q abnormality. Azacytidine and decitabine have been demonstrated to improve blood counts, improve the quality of life, and decrease the risk of progression to AML or death in a sizable minority of MDS patients. A recent study of MDS patients who had responded clinically to decitabine revealed that their bone marrow biopsies still showed stromal abnormalities such as increased angiogenesis. Lenalidomide acts at the level of the stromal - marrow cell interaction. It is hypothesized that the combination of decitabine with lenalidomide may show synergistic results.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Myelodysplastic Syndromes
Drug: Lenalidomide, Decitabine
Decitabine 20mg/m2 over one hour IV for 5 days, with cycles repeated every 28 days. Lenalidomide given orally on Days 1-21 followed by 7 days of rest at various dose escalated cohorts (5 mg, 10mg, 15mg, 20 mg, 25 mg)
Other Names:
  • revlimid
  • Dacogen
  • Experimental: Cohort 1
    Lenalidomide (5mg) and Decitabine
    Intervention: Drug: Lenalidomide, Decitabine
  • Experimental: Cohort 2
    Lenalidomide (10 mg) and Decitabine
    Intervention: Drug: Lenalidomide, Decitabine
  • Experimental: Cohort 3
    Lenalidomide (15 mg) and Decitabine
    Intervention: Drug: Lenalidomide, Decitabine
  • Experimental: Cohort 4
    Lenalidomide (20 mg) and Decitabine
    Intervention: Drug: Lenalidomide, Decitabine
  • Experimental: Cohort 5
    Lenalidomide (25 mg) and Decitabine
    Intervention: Drug: Lenalidomide, Decitabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
November 2012
August 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form.
  • Age >/=18 years at the time of signing the informed consent form.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Myelodysplastic syndrome (documented by bone marrow biopsy) with IPSS score of Int-2 or High risk.
  • All previous MDS therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 28 days prior to treatment in this study.
  • ECOG performance status of </= 2 at study entry.
  • Laboratory test results within these ranges: Serum creatinine </= 2.5 mg/dL x ULN, Total bilirubin </= 2.5 mg/dL x ULN, AST (SGOT) and ALT (SGPT) </= 3 x ULN.
  • All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
  • Females of childbearing potential must have a negative serum pregnancy test within 10-14 days prior to and again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. Must also agree to ongoing pregnancy testing.
  • Men must agree to use a latex condom during sexual contact even if they have had a successful vasectomy.
  • Disease free of prior malignancies for >/= 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, localized prostate cancer, or carcinoma "insitu" of the cervix or breast.

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric
  • Pregnant or breast feeding females.
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Known hypersensitivity or reaction to thalidomide, lenalidomide or decitabine.
  • Any prior use of lenalidomide.
  • Concurrent use of other anti-cancer agents or anti-cancer treatments.
  • Known positive for HIV or active infectious hepatitis, type A, B or C.
  • History of thromboembolic event within past 6 months prior to enrollment.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00828802
Pro00010179
No
Duke University
Duke University
Celgene Corporation
Principal Investigator: Carlos de Castro, MD Duke University
Duke University
September 2013

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