Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation

NCT00593645 | Terminated Phase 2 Results DMC

• 2 other identifiers: 07-0702No grant number
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Six-month Treatment Related Mortality

  6 months

Secondary Outcomes (10)

• Disease Specific Response Rates

  One, three, six and twelve months.

• Engraftment as Measured by Percent Donor Chimerism

  Day +30

• Engraftment as Measured by Percent Donor Chimerism

  Day +40-+60

• Engraftment as Measured by Percent Donor Chimerism

  Day +80-+90

• Overall Survival

  5 years from time of restaging

Study Arms (1)

Arm 1: Non-myeloablative conditioning regimen

EXPERIMENTAL

* 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; Drug: Cytarabine; Drug: Thymoglobulin; Procedure: Stem cell infusion

Interventions

Clofarabine DRUG

Also known as: Clolar

Arm 1: Non-myeloablative conditioning regimen

Cytarabine DRUG

Also known as: Ara-C, Cytosar

Arm 1: Non-myeloablative conditioning regimen

Thymoglobulin DRUG

Also known as: Anti-thymocyte globulin

Arm 1: Non-myeloablative conditioning regimen

Stem cell infusion PROCEDURE

Also known as: Stem cell transplant, Hematopoietic stem cell transplant, Peripheral blood stem cell transplant, Bone marrow transplant

Arm 1: Non-myeloablative conditioning regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Patients may be in any CR
• No more than 2 cycles of consolidation. Any consolidation regimen may be used.
• No more than 6 months from documented CR to transplant.
• Age 18 years or older.
• ECOG performance status \<=2
• Identification of suitable donor
• DLCO \>=40% with no symptomatic pulmonary disease
• LVEF by MUGA \>= 30%
• 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).
• Bilirubin \<=2 times the upper limit of normal
• AST \<=3 times the upper limit of normal
• Donor criteria:
• 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.
• Matched Unrelated Donor: An acceptable match per NMDP standards based on high resolution molecular typing.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Ravi Vij, M.D.

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Clofarabine; Cytarabine; thymoglobulin; Antilymphocyte Serum; Stem Cell Transplantation; Peripheral Blood Stem Cell Transplantation; Bone Marrow Transplantation

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Hematopoietic Stem Cell Transplantation; Tissue Transplantation

Limitations and Caveats

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.

Results Point of Contact

• Title: Ravi Vij, M.D.
• Organization: Washington University School of Medicine

rvij@dom.wustl.edu

314-454-8304

Study Officials

• Ravi Vij, M.D.

  Washington Universtiy of St. Louis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2008
• First Posted: January 15, 2008
• Study Start: November 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: July 1, 2009
• Last Updated: September 12, 2014
• Results First Posted: September 12, 2014

Record last verified: 2014-09

Locations

US (1)