Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00593645
• Other study ID #: 07-0702
• Secondary ID: No grant number
• Status: Terminated
• Phase: Phase 2
• First received: January 2, 2008
• Last updated: September 5, 2014
• Start date: November 2007
• Est. completion date: July 2009

Study information

• Verified date: September 2014
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: July 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Clofarabine

• Cytarabine

• Thymoglobulin

Procedure:
• Stem cell infusion

Locations

Country	Name	City	State
United States	Ravi Vij, M.D.	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Six-month Treatment Related Mortality		6 months	Yes
Secondary	Disease Specific Response Rates	Disease-specific partial response and complete response.	One, three, six and twelve months.	No
Secondary	Engraftment as Measured by Percent Donor Chimerism		Day +30	No
Secondary	Engraftment as Measured by Percent Donor Chimerism		Day +40-+60	No
Secondary	Engraftment as Measured by Percent Donor Chimerism		Day +80-+90	No
Secondary	Overall Survival		5 years from time of restaging	No
Secondary	Disease-free Survival	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.	5 years from time of restaging	No
Secondary	Rate of Acute Graft-versus-host Disease (GVHD)	Acute GVHD occurs within 100 days of transplant.	Up to 100 days after transplant	Yes
Secondary	Rate of Chronic Graft-versus-host Disease (GVHD)		100 days-1 year after transplant	Yes
Secondary	Use Conventional STR-PCR Method for Monitoring Engraftment	Includes assessment of mixed chimerism in the whole blood, myeloid cells, T cells, and B cells.	Up to 1 year after transplant	No
Secondary	Median Time to Progression	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.	5 years from time of restaging	No

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine