Cyclophosphamide, Antithymocyte Globulin, and Total-Body Irradiation in Treating Patients With Severe Aplastic Anemia Undergoing Umbilical Cord Blood Transplant - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00354419

Purpose

RATIONALE: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of total-body irradiation when given together with cyclophosphamide and antithymocyte globulin in treating patients with severe aplastic anemia undergoing umbilical cord blood transplant.

Condition	Intervention	Phase
Aplastic Anemia	Radiation: total-body irradiation Drug: cyclophosphamide Biological: anti-thymocyte globulin Drug: cyclosporine Procedure: umbilical cord blood transplantation Drug: mycophenolate mofetil Procedure: bone marrow aspiration Genetic: DNA analysis Biological: filgrastim	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Dose Finding Study of Total Body Irradiation for Conditioning Patients With Severe Aplastic Anemia Transplanted With Umbilical Cord Blood

Resource links provided by NLM:

MedlinePlus related topics: Anemia Aplastic Anemia Cancer

Drug Information available for: Cyclophosphamide Cyclosporine Cyclosporin Granulocyte-macrophage colony-stimulating factor Mycophenolate mofetil hydrochloride Filgrastim Sargramostim Mycophenolate Mofetil Lenograstim Granulocyte colony-stimulating factor Immunoglobulins Globulin, Immune

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Engraftment [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	February 2006
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I See Detailed Description	Radiation: total-body irradiation Undergo radiotherapy Other Name: TBI Drug: cyclophosphamide Given IV Other Names: CPM CTX Cytoxan Endoxan Endoxana Enduxan Biological: anti-thymocyte globulin Given IV Other Names: ATG ATGAM lymphocyte immune globulin Thymoglobulin Drug: cyclosporine Given IV Other Names: 27-400 ciclosporin cyclosporin cyclosporin A CYSP Sandimmune Procedure: umbilical cord blood transplantation Undergo transplantation Other Names: cord blood transplantation transplantation, umbilical cord blood UCB transplantation Drug: mycophenolate mofetil Given IV or orally Other Names: Cellcept MMF Procedure: bone marrow aspiration Correlative study Genetic: DNA analysis Correlative study Biological: filgrastim Given IV or SC Other Names: G-CSF granulocyte colony-stimulating factor Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

Arms

Assigned Interventions

Experimental: Arm I

See Detailed Description

Radiation: total-body irradiation

Undergo radiotherapy

Other Name: TBI

Drug: cyclophosphamide

Given IV

Other Names:

CPM
CTX
Cytoxan
Endoxan
Endoxana
Enduxan

Biological: anti-thymocyte globulin

Given IV

Other Names:

ATG
ATGAM
lymphocyte immune globulin
Thymoglobulin

Drug: cyclosporine

Given IV

Other Names:

27-400
ciclosporin
cyclosporin
cyclosporin A
CYSP
Sandimmune

Procedure: umbilical cord blood transplantation

Undergo transplantation

Other Names:

cord blood transplantation
transplantation, umbilical cord blood
UCB transplantation

Drug: mycophenolate mofetil

Given IV or orally

Other Names:

Cellcept
MMF

Procedure: bone marrow aspiration

Correlative study

Genetic: DNA analysis

Correlative study

Biological: filgrastim

Given IV or SC

Other Names:

G-CSF
granulocyte colony-stimulating factor
Neupogen
r-metHuG-CSF
Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

Detailed Description:

OBJECTIVES:

I. The objective of this study is to determine the lowest dose of total body irradiation combined with cyclophosphamide and antithymocyte globulin that will achieve sustained engraftment in patients with severe aplastic anemia transplanted with unrelated umbilical cord blood.

OUTLINE: This is a dose-escalation study of total-body irradiation (TBI).

MYELOABLATIVE CONDITIONING REGIMEN: Patients receive cyclophosphamide IV on days -7 to -4, -6 to -3, or -5 to -2 and antithymocyte globulin IV on days -6 to -4, -5 to -3, or -4 to -2.

TBI: Patients undergo TBI twice daily on days -3, -2, and/or -1.

UMBILICAL CORD BLOOD TRANSPLANTATION (UCBT): Patients undergo UCBT on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover.

GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine IV or orally (twice daily for patients >= 6 years of age or 3 times daily for patients < 6 years of age) on days -1 to +180 and mycophenolate mofetil IV or orally (twice daily for patients >= 50 kg or 3 times daily for patients < 50 kg) beginning 4 hours after UCBT and continuing until approximately day +0.

After completion of study therapy, patients are followed periodically.

Eligibility

Ages Eligible for Study:	up to 40 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Life-threatening marrow failure of nonmalignant etiology meeting two of the three following criteria: granulocytes < 500/mm^3; a corrected reticulocyte count < 1%; platelet count < 20,000/mm^3
Failure to respond to the best available immunosuppressive treatment protocol by 75 days after initiation of therapy
Lack of an HLA-identical family member or closely matched (9 or 10 of 10 HLA-locus match) unrelated marrow donor
DONOR: Unrelated UCB unit matched for at least 4 of 6 loci
DONOR: Related UCB unit matched for at least 3 of 6 lock
Selection of the UCB unit(s) will be based upon matching or mismatching at HLA-A, B antigen level and DRB1 allele level typing; while HLA-C antigen/allele and HLA-DQB1 antigen/allele level typing are not considered in the matching criteria, if available each may be used to optimize unit selection
Multiple UCB units are allowed to provide sufficient cell dose; when multiple units are selected, the following rules apply: a) the UCB unit with the least HLA disparity will be selected first (i.e., selection priority is 6/6 match > 5/6 match > 4/6 match), additional UCB units may be selected to increase cell dose; b) UCB units must be matched to each other for at least 4 of 6 loci; c) each unit must contain at least 1.5 x 10^7 Total Nucleated Cells per kg recipient weight; d) the total cell dose of the combined units must be at least 3.0 x 10^7 Total Nucleated Cells per kg recipient weight

Exclusion Criteria:

Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure; patients who present with active fungal infections must be treated to resolve this problem before beginning the conditioning regimen
HIV seropositive patients
Patients who have developed clonal cytogenetic abnormalities or a myelodysplastic syndrome (these patients will be considered in separate protocols for myelodysplastic syndrome, etc.)
Patients with paroxysmal nocturnal hemoglobinuria or Fanconi anemia
Patients > 40 years of age
Related or unrelated cord blood units with < 1.5 x 10^7 Total Nucleated Cells per kg recipient weight
Related or unrelated cord blood units without full testing and negative results for hepatitis A, B, C, HIV, HTLV-1, CMV viruses

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354419

Locations

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Ann Woolfrey

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

More Information

No publications provided

Responsible Party:	Woolfrey, Ann, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier:	NCT00354419 History of Changes
Other Study ID Numbers:	2030.00, NCI-2010-00191
Study First Received:	July 19, 2006
Last Updated:	January 3, 2011
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Antilymphocyte Serum
Cyclophosphamide
Cyclosporine
Cyclosporins
Mycophenolate mofetil
Immunoglobulins
Lenograstim
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Enzyme Inhibitors
Antibiotics, Antineoplastic
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on February 12, 2012