Clinical trial NCT00593645: Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation
Official title: A Non-Myeloablative Conditioning Regimen for Allogeneic Transplantation With Clofarabine, Cytarabine, and Thymoglobulin for Myelodysplastic Syndrome and Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Acute Myeloid Leukemia
Keywords: Conditioning regimens
Stem Cell Transplantation
Hematopoietic Stem Cell Transplantation
Allogeneic Stem Cell Transplantation
Nonmyeloablative conditioning
Clofarabine
Cytarabine
Anti-thymocyte globulin
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2008-01-15
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Six-month Treatment Related Mortality
timeFrame: 6 months
Secondary outcomes:
measure: Disease Specific Response Rates
timeFrame: One, three, six and twelve months.
measure: Engraftment as Measured by Percent Donor Chimerism
timeFrame: Day +30
measure: Engraftment as Measured by Percent Donor Chimerism
timeFrame: Day +40-+60
measure: Engraftment as Measured by Percent Donor Chimerism
timeFrame: Day +80-+90
measure: Overall Survival
timeFrame: 5 years from time of restaging
measure: Disease-free Survival
timeFrame: 5 years from time of restaging
measure: Rate of Acute Graft-versus-host Disease (GVHD)
timeFrame: Up to 100 days after transplant
measure: Rate of Chronic Graft-versus-host Disease (GVHD)
timeFrame: 100 days-1 year after transplant
measure: Use Conventional STR-PCR Method for Monitoring Engraftment
timeFrame: Up to 1 year after transplant
measure: Median Time to Progression
timeFrame: 5 years from time of restaging
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Ravi Vij, M.D.
state: Missouri
Study officials:
affiliation: Washington Universtiy of St. Louis
name: Ravi Vij, M.D.
role: PRINCIPAL_INVESTIGATOR
References: