Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation

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. Identifier: NCT00593645
Recruitment Status : Terminated (toxicities were worse than expected)
First Posted : January 15, 2008
Results First Posted : September 12, 2014
Last Update Posted : September 12, 2014
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
This study will test the combination of clofarabine, cytarabine, and thymoglobulin as a non-myeloablative conditioning regimen for patients with myelodysplastic syndromes or acute myeloid leukemia undergoing allogeneic stem cell transplant.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Acute Myeloid Leukemia Drug: Clofarabine Drug: Cytarabine Drug: Thymoglobulin Procedure: Stem cell infusion Phase 2

Detailed Description:
Current reduced intensity conditioning regimens have been able to decrease TRM (treatment related mortality) but suffer from increased rates of disease relapse. Disease burden at transplantation, as measured by percent myeloblasts, predicts relapse. Current regimens employ fludarabine and busulfan with various adjutants, but these agents are not part of the usual armamentarium used versus leukemia and have questionable anti-leukemic activity. By substituting clofarabine and cytarabine, a combination with proven anti-leukemic activity in the relapsed and refractory setting as well as activity versus MDS, as the back bone of the regimen we hope overcome residual disease and improve post-transplant relapse rates. Furthermore the principal toxicity of this regimen is myelosuppression, which should be abrogated by the infusion of stem cells. Thymoglobulin is included due to its minimal contribution to toxicity but significant benefits in engraftment, and controlling acute and chronic GVHD, which are major contributors to TRM and disease specific activity in MDS.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Non-Myeloablative Conditioning Regimen for Allogeneic Transplantation With Clofarabine, Cytarabine, and Thymoglobulin for Myelodysplastic Syndrome and Acute Myeloid Leukemia
Study Start Date : November 2007
Actual Primary Completion Date : December 2008
Actual Study Completion Date : July 2009

Arm Intervention/treatment
Experimental: Arm 1: Non-myeloablative conditioning regimen
  • Clofarabine 40mg/m2/day IV over two hours daily x 5 days on Days -6 thru -2
  • Cytarabine 1gm/m2/day IV over two hours daily x 5 days on Days -6 thru -2 after the START of Clofarabine.
  • Thymoglobulin 1.0mg/kg IV over 6 hours X 1 day on Day -4, then 2.5mg/kg/day x 2 days on Days -3 and -2.
  • Stem Cell Transplant - On day 0 a minimum of total CD34+ cell dose of 2 x10E6/kg (actual weight of recipient) will be infused.
Drug: Clofarabine
Other Name: Clolar

Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar

Drug: Thymoglobulin
Other Name: Anti-thymocyte globulin

Procedure: Stem cell infusion
Other Names:
  • Stem cell transplant
  • Hematopoietic stem cell transplant
  • Peripheral blood stem cell transplant
  • Bone marrow transplant

Primary Outcome Measures :
  1. Six-month Treatment Related Mortality [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Disease Specific Response Rates [ Time Frame: One, three, six and twelve months. ]
    Disease-specific partial response and complete response.

  2. Engraftment as Measured by Percent Donor Chimerism [ Time Frame: Day +30 ]
  3. Engraftment as Measured by Percent Donor Chimerism [ Time Frame: Day +40-+60 ]
  4. Engraftment as Measured by Percent Donor Chimerism [ Time Frame: Day +80-+90 ]
  5. Overall Survival [ Time Frame: 5 years from time of restaging ]
  6. Disease-free Survival [ Time Frame: 5 years from time of restaging ]
    Disease-free survival is defined as the length of time after treatment ends that the participant survives without any signs or symptoms of that cancer.

  7. Rate of Acute Graft-versus-host Disease (GVHD) [ Time Frame: Up to 100 days after transplant ]
    Acute GVHD occurs within 100 days of transplant.

  8. Rate of Chronic Graft-versus-host Disease (GVHD) [ Time Frame: 100 days-1 year after transplant ]
  9. Use Conventional STR-PCR Method for Monitoring Engraftment [ Time Frame: Up to 1 year after transplant ]
    Includes assessment of mixed chimerism in the whole blood, myeloid cells, T cells, and B cells.

  10. Median Time to Progression [ Time Frame: 5 years from time of restaging ]
    Time to progression is defined as the length of time from the start of treatment until the disease starts to get worse or spread to other parts of the body.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria (Patient):

  1. Myelodysplastic Syndrome (MDS), as defined by the World Health Organization criteria, OR Chronic Myelomonocytic Leukemia (CMML) as defined by the French American British classification OR Acute Myeloid Leukemia (AML) in complete remission [excluding FAB-M3] diagnosed by standard criteria and meet the criteria below:

    1. Patients may be in any CR
    2. No more than 2 cycles of consolidation. Any consolidation regimen may be used.
    3. No more than 6 months from documented CR to transplant.
  2. Age 18 years or older.
  3. ECOG performance status <=2
  4. Identification of suitable donor
  5. DLCO >=40% with no symptomatic pulmonary disease
  6. LVEF by MUGA >= 30%
  7. Serum creatinine <=1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black).
  8. Bilirubin <=2 times the upper limit of normal
  9. AST <=3 times the upper limit of normal

Donor criteria:

  1. HLA-Matched Sibling: The donor must be an adequate HLA match as determined by serologic typing for class (A, B) and low resolution molecular typing for class II (DRB1) as defined by institutional standards.
  2. Matched Unrelated Donor: An acceptable match per NMDP standards based on high resolution molecular typing.
  3. The donor must be healthy and must be an acceptable donor as per institutional standards for stem cell collection.
  4. The donor must have no significant cardiopulmonary, renal, endocrine, or hepatic disease.
  5. There is no upper age restriction for donors, but they must be at least 18 years of age.
  6. Syngeneic donors are not eligible.
  7. No known HIV.

Exclusion Criteria:

  1. Pregnant or nursing.
  2. Active systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment.
  3. Severe concurrent disease, including severe insulin-dependent diabetes, uncontrolled hypertension, transient ischemic attacks, uncontrolled symptomatic coronary artery disease, or symptomatic CNS involvement or psychiatric illness/social situations that would limit compliance with study requirements.
  4. Known HIV disease.
  5. History of other malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast unless the subject has been off treatment and free from disease for > 3 years.
  6. Active disease at the time of transplant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00593645

Layout table for location information
United States, Missouri
Ravi Vij, M.D.
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Layout table for investigator information
Principal Investigator: Ravi Vij, M.D. Washington Universtiy of St. Louis
Additional Information:
Layout table for additonal information
Responsible Party: Washington University School of Medicine Identifier: NCT00593645    
Other Study ID Numbers: 07-0702
No grant number
First Posted: January 15, 2008    Key Record Dates
Results First Posted: September 12, 2014
Last Update Posted: September 12, 2014
Last Verified: September 2014
Keywords provided by Washington University School of Medicine:
Conditioning regimens
Stem Cell Transplantation
Hematopoietic Stem Cell Transplantation
Allogeneic Stem Cell Transplantation
Nonmyeloablative conditioning
Anti-thymocyte globulin
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antilymphocyte Serum
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs