Reduced Intensity Conditioning With Clofarabine, Antithymocyte Globulin (ATG), Total Lymphoid Irradiation (TLI) Following an Allogeneic Stem Cell Transplant - Full Text View

Sponsors and Collaborators:	Dana-Farber Cancer Institute Genzyme
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00697684

Purpose

This study will examine the safety of clofarabine, TLI and ATG as a reduced conditioning regimen prior to allogeneic transplantation. The impact of the conditioning regimen on the presence of the circulating regulatory as compared to activated T cell populations will be assessed.The recovery of DC populations post-transplant will be examined, along with the effect of the regimen on disease free and overall survival.

Condition	Intervention	Phase
Acute Myeloid Leukemia Myelodysplastic Syndrome Acute Lymphocytic Leukemia Relapsed/Refractory Chronic Lymphocytic Leukemia Relapsed/Refractory Non Hodgkin's Lymphoma Hodgkins Disease Relapsed Refractory Multiple Myeloma	Drug: Antithymocyte Globulin Drug: Clofarabine	Phase I

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Multiple Myeloma

Drug Information available for: Clofarabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment
Official Title:	A Reduced Intensity Conditioning With Clofarabine Antithymocyte Globulin and Total Lymphoid Irradiation Followed by Allogeneic Hematopoietic Stem Cell Transplantation

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

To assess the toxicity and donor engraftment following treatment with a reduced intensity preparative regimen consisting of clofarabine, rabbit antithymocyte globulin (ATG), and total lymphoid irradiation followed by the infusion of allogeneic stem cells [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine the incidence of acute and chronic graft versus host disease following clofarabine, rabbit ATG, total lymphoid irradiation, and allogeneic transplantation. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
2. To evaluate the nature of immunologic reconstitution in patients treated clofarabine, rabbit ATG, total lymphoid irradiation, and allogeneic transplantation. The impact of the regimen on the phenotypic and functional characteristics of dendritic cell [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To determine the disease free survival and overall survival of patients undergoing allogeneic transplantation following following clofarabine, rabbit ATG, and total lymphoid irradiation. [ Time Frame: Patient lifetime ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	June 2008
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Cohort 1: No Intervention	Drug: Antithymocyte Globulin Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).
Cohort 2: Experimental	Drug: Clofarabine Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 20mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 100 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).
Cohort 3: Experimental	Drug: Clofarabine Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 30mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 150 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).
Cohort 4: Experimental	Drug: Clofarabine Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 40mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 200 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).

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Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with a)acute myeloid leukemia exclusive of patients in first complete remission with good risk cytogenetics (translocation 8,21,translocation 15, 17 or inversion 16); B)myelodysplastic syndrome; c)acute lymphocytic leukemia exclusive of patients in first remission without negative prognostic markers; d) relapsed or refractory nonHodgkin's lymphoma or Hodgkin's disease; e)relapsed or refractory multiple myeloma or f)relapsed or refractory chronic lymphocytic leukemia.
Patients who are considered appropriate for reduced intensity transplantation must present with at least one of the following: A. Age over 50 B. History of a prior hematopoietic stem cell transplant C. Patient with compromised organ function or comorbid conditioning such that a standard ablative transplant would be considered high risk.
Patients will have a related or unrelated donor matched at 5/6 or 6/6 HLA loci.
Patients must be greater than or equal to 18 years old, and younger than or equal to 70 years old to participate in the study.
Patients must have ECOG performance status of 0-2
Pulmonary function tests demonstrate DLCO (adjusted for Hgb)>50% predicted
Cardiac ejection fraction >40%
Laboratories:
- Bilirubin less than or equal to 1.5mg/dL x ULN
- AST/ALT/Alkaline Phosphatase less than or equal to 2.5x ULN
- Serum creatinine less than or equal to 1.0mg/dL; if serum creatinine > 1.0MG/dL, then the estimated glomerular filtration rate (GFR) must be >60mL/min/1.73m^2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GRF (ml/min/1.73m^2)=186x (serum creatinine)^1.154x(age in years)^-0.023x(0.742 if patient is female) x (1.212 if patient is black)
Patients with serologic evidence of hepatitis B or C exposure will undergo liver biopsy to assess for presence of active hepatitis or fibrosis and quantification of risk of proceeding with transplant.

10. All patients must be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. All patients must be informed of the investigational nature of this study and must give written informed consent in accordance with institutional and federal guidelines.

11. Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.

12. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment

Exclusion Criteria:

Patients who are HIV+ will be excluded.
Patients must not have serious intercurrent illness such as uncontrolled systemic infection or significant organ compromise which significantly increases the risk of undergoing allogeneic transplantation.
Pregnant and lactating women will be excluded.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697684

Contacts

Contact: Carol Delaney, RN	617-667-1969	cdelaney@bidmc.harvard.edu
Contact: Jessica Bonhoff	617-667-1903	jbonhoff@bidmc.harvard.edu

Locations

United States, Massachusetts
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Carol Delaney, RN 617-667-1969 cdelaney@bidmc.harvard.edu
Principal Investigator: David Avigan, MD
Sub-Investigator: Jacalyn Rosenblatt, MD
Sub-Investigator: Robin Joyce, MD
Sub-Investigator: James D Levine, MD
Sub-Investigator: Jeffrey Zwicker, MD
Sub-Investigator: Mary Ann Stevenson, MD
Massachusetts General Hospital	Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Joanne Kennedy, RN 617-726-6034 jkennedy9@partners.org
Principal Investigator: Thomas Spitzer, MD

Sponsors and Collaborators

Dana-Farber Cancer Institute

Genzyme

Investigators

Principal Investigator:

David E Avigan, MD

Beth Israel Deaconess Medical Center

More Information

Responsible Party:	Beth Israel Deaconess Medical Center ( David Avigan, MD )
Study ID Numbers:	07-384
Study First Received:	June 12, 2008
Last Updated:	July 14, 2008
ClinicalTrials.gov Identifier:	NCT00697684
Health Authority:	United States: Institutional Review Board; United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

Reduced Intensity Allogeneic Stem Cell Transplant
Clofarabine
Rabbit Antithymocyte Globulin
Total Lymphoid Radiation

Study placed in the following topic categories:

Leukemia, Lymphoid
Hodgkin's disease
Precancerous Conditions
Blood Protein Disorders
Hodgkin lymphoma, adult
Lymphoma, small cleaved-cell, diffuse
Paraproteinemias
Leukemia, Myeloid, Acute
Hemostatic Disorders
Leukemia
Preleukemia
Hemorrhagic Disorders
Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Acute myelocytic leukemia

Hodgkin Disease
Lymphoma
Clofarabine
Chronic lymphocytic leukemia
Myelodysplastic syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, B-cell, chronic
Blood Coagulation Disorders
Myelodysplasia
Myelodysplastic Syndromes
Acute myelogenous leukemia
Vascular Diseases
Leukemia, Myeloid

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Disease
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Pathologic Processes
Syndrome
Therapeutic Uses
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 15, 2009