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Cytarabine

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Clofarabine

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Immunologic Factors

* 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.

Stem cell infusion

Ravi Vij, M.D.

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.

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.

Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation

A Non-Myeloablative Conditioning Regimen for Allogeneic Transplantation With Clofarabine, Cytarabine, and Thymoglobulin for Myelodysplastic Syndrome and Acute Myeloid Leukemia

Disease-specific partial response and complete response.

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.

Acute GVHD occurs within 100 days of transplant.

Includes assessment of mixed chimerism in the whole blood, myeloid cells, T cells, and B cells.

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.

Washington University School of Medicine

Arm 1

Arm 1: Non-myeloablative Conditioning Regimen

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Myelodysplastic syndrome

Acute myeloid leukemia

Diagnosis

Enrollment was halted after 3 of the first 7 patients expired on days 15/26/32. Predefined early stopping rules were defined that if three deaths occurred in the first 11 patients then it was unlikely to achieve a low treatment-related mortality.

This outcome was not analyzed.

Enrollment to the trial was halted after three of the first seven patients expired. This fulfilled the predefined stopping rule as it was unlikely that we would achieve our primary end point of a 6 month treatment-related mortality of 10%.

Six-month Treatment Related Mortality

This outcome was not analyzed due to terminating the study after 7 participants were enrolled.

We felt that the engraftment as measured by percent donor chimerism provided better response details than the limited data that was collected for the disease specific partial and complete response rates.

Disease Specific Response Rates

Not done

50% donor (bone marrow)

100% donor (bone marrow)

23.5% donor (FISH)

2 participants were not analyzed because they expired prior to Day +30.

Engraftment as Measured by Percent Donor Chimerism

60% donor (bone marrow)

70% donor (bone marrow)

75% donor (bone marrow)

100% donor (peripheral blood)

3 participants were not analyzed because they were expired.

0% donor

33% donor - myeloid (peripheral blood)

67% donor (bone marrow)

3 participants were not analyzed as they were deceased.

Overall Survival

None of the patients analyzed survived without any signs or symptoms of that cancer.

Disease-free Survival

Rate of Acute Graft-versus-host Disease (GVHD)

None of the participants had chronic graft-versus-host disease (GVHD). 3 participants expired prior to day 100.

Rate of Chronic Graft-versus-host Disease (GVHD)

This outcome was not analyzed specifically as the conventional STR-PCR method was used for monitoring engraftment.

Use Conventional STR-PCR Method for Monitoring Engraftment

Of the four surviving patients, three relapsed. One patient remained in remission on day +120.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation	NCT00593645	Myelodysplastic... Acute Myeloid L...	Clofarabine Cytarabine Thymoglobulin Stem cell infus...	18 Years -	Washington University School of Medicine
Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation	NCT00593645	Myelodysplastic... Acute Myeloid L...	Clofarabine Cytarabine Thymoglobulin Stem cell infus...	18 Years -	Washington University School of Medicine

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