Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation

Phase 2

Terminated

Conditions: Myelodysplastic Syndromes
Acute Myeloid Leukemia

Interventions: Drug: Clofarabine
Drug: Cytarabine
Drug: Thymoglobulin
Procedure: Stem cell infusion

Registration Number: NCT00593645

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 7

Inclusion Criteria

Not provided

Exclusion Criteria

Pregnant or nursing.
Active systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment.
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.
Known HIV disease.
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.
Active disease at the time of transplant.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1: Non-myeloablative conditioning regimen	Stem cell infusion	* 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.
Arm 1: Non-myeloablative conditioning regimen	Clofarabine	* 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.
Arm 1: Non-myeloablative conditioning regimen	Cytarabine	* 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.
Arm 1: Non-myeloablative conditioning regimen	Thymoglobulin	* 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.

Primary Outcome Measures

Name	Time	Method
Six-month Treatment Related Mortality	6 months

Secondary Outcome Measures

Name	Time	Method
Disease Specific Response Rates	One, three, six and twelve months.	Disease-specific partial response and complete response.
Rate of Acute Graft-versus-host Disease (GVHD)	Up to 100 days after transplant	Acute GVHD occurs within 100 days of transplant.
Engraftment as Measured by Percent Donor Chimerism	Day +80-+90
Overall Survival	5 years from time of restaging
Rate of Chronic Graft-versus-host Disease (GVHD)	100 days-1 year after transplant
Disease-free Survival	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.
Use Conventional STR-PCR Method for Monitoring Engraftment	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	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.