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Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation

This study has been terminated.
(toxicities were worse than expected)
Information provided by (Responsible Party):
Washington University School of Medicine Identifier:
First received: January 2, 2008
Last updated: September 5, 2014
Last verified: September 2014
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 Intervention Phase
Myelodysplastic Syndromes Acute Myeloid Leukemia Drug: Clofarabine Drug: Cytarabine Drug: Thymoglobulin Procedure: Stem cell infusion Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:

Further study details as provided by Washington University School of Medicine:

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

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

  • Engraftment as Measured by Percent Donor Chimerism [ Time Frame: Day +30 ]
  • Engraftment as Measured by Percent Donor Chimerism [ Time Frame: Day +40-+60 ]
  • Engraftment as Measured by Percent Donor Chimerism [ Time Frame: Day +80-+90 ]
  • Overall Survival [ Time Frame: 5 years from time of restaging ]
  • 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.

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

  • Rate of Chronic Graft-versus-host Disease (GVHD) [ Time Frame: 100 days-1 year after transplant ]
  • 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.

  • 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.

Enrollment: 7
Study Start Date: November 2007
Study Completion Date: July 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT00593645

United States, Missouri
Ravi Vij, M.D.
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Principal Investigator: Ravi Vij, M.D. Washington Universtiy of St. Louis
  More Information

Additional Information:
Responsible Party: Washington University School of Medicine Identifier: NCT00593645     History of Changes
Other Study ID Numbers: 07-0702
No grant number
Study First Received: January 2, 2008
Results First Received: July 18, 2014
Last Updated: September 5, 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:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Pathologic Processes
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 processed this record on September 21, 2017