Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation

This study has been terminated.
(toxicities were worse than expected)
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00593645
First received: January 2, 2008
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

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: 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:
  • To determine the six-month treatment related mortality for a conditioning regimen composed of clofarabine, cytarabine, and thymoglobulin for allogeneic transplantation of myelodysplastic syndromes and acute myeloid leukemia. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To describe the response rates for patients treated on this protocol. [ Time Frame: At one, three, six and twelve months. ] [ Designated as safety issue: No ]
    Disease-specific partial response and complete response. Also time-to-progression for responding patients.

  • Determine percent donor chimerism achieved with this treatment [ Time Frame: At day +30, +60, and +90 ] [ Designated as safety issue: No ]
  • Overall survival and disease-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Use conventional STR-PCR method for monitoring engraftment [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Includes assessment of mixed chimerism in the whole blood, myeloid cells, T cells, and B cells.

  • Determine the acute and chronic graft-versus-host disease and other toxicities [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

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
  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00593645

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

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00593645     History of Changes
Other Study ID Numbers: 07-0702, No grant number
Study First Received: January 2, 2008
Last Updated: August 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Conditioning regimens
Stem Cell Transplantation
Hematopoietic Stem Cell Transplantation
Allogeneic Stem Cell Transplantation
Nonmyeloablative conditioning
Clofarabine
Cytarabine
Anti-thymocyte globulin

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antilymphocyte Serum
Cytarabine
Clofarabine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 01, 2014