Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

This study has been withdrawn prior to enrollment.
(This study did not accrue any subjects and due to this will be closed.)
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01129323
First received: April 21, 2010
Last updated: March 23, 2012
Last verified: March 2012
  Purpose

The purpose of this study is to evaluate the effectiveness of allogeneic transplant after a reduced-intensity preparative regimen for patient, to evaluate survival, and to evaluate the side effects of this treatment. The patient will be in the study for two years for treatment and active monitoring. After treatment and active monitoring are over, the patient's medical condition will be followed indefinitely.


Condition Intervention
Severe Aplastic Anemia
Drug: Cyclophosphamide, Fludarabine, Rabbit ATG

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Engraftment rate [ Time Frame: Day 42 after allogeneic transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Relapse [ Time Frame: Days 180, 365 and yearly post transplant ] [ Designated as safety issue: Yes ]
  • Development of Graft vs. Host Disease [ Time Frame: Days 180, 365 and yearly post transplant ] [ Designated as safety issue: Yes ]
  • Evaluation of the occurrence of secondary malignancies [ Time Frame: Days 180, 365 and yearly post transplant ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: Days 180, 365 and yearly post transplant ] [ Designated as safety issue: Yes ]
  • Evaluation of treatment feasibility [ Time Frame: Days 180, 365 and yearly post transplant ] [ Designated as safety issue: Yes ]
  • Evaluation of toxicities [ Time Frame: Days 180, 365 and yearly post transplant ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: November 2009
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Reduced-Intensity Preparative Regimen for Allogeneic SCT
Patient in this arm will receive maximally tolerated (reduced) doses of cytotoxic therapy with the goals of suppressing the immune system, and ablate host hematopoiesis to ensure engraftment of the donor's hematopoietic system.
Drug: Cyclophosphamide, Fludarabine, Rabbit ATG
Fludarabine 30mg/m2/dose IV and cyclophosphamide 10mg/kg/dose IV are given once per day from day -5 to -2. rATG 1.5 mg/kg/dose IV is given from day -4 to -1.

Detailed Description:

Aplastic Anemia is a blood disorder where bone marrow does not produce enough cells for blood. Patients with aplastic anemia have lower counts of all three blood cell types (RBC, WBC, and Platelet). Severe cases of aplastic anemia that are untreated can lead to death from bleeding and overwhelming infection.

For patients with Severe Aplastic Anemia (SAA), allogeneic hematopoietic stem cell transplant (HSCT) from an HLA-identical sibling is an accepted treatment for restoring normal bone marrow function. Preparative regimens for allogeneic HSCT are designed to give the highest tolerated doses of chemotherapy, with or without total body irradiation (TBI), in order to fully "ablate" or destroy the patient host's bone marrow so that the transplanted cells from the HLA-identical sibling can engraft in the patient host.

While allogeneic HSCT has been proven to be a curative form of therapy for SAA, it is also associated with high transplant-related morbidity (side effects) and possible mortality (death). One of the toxic side effects from high-dose chemotherapy and TBI are believed to be a major contributing factor to "Graft-versus-Host Disease" (GVHD).

Preliminary studies have shown that a reduced intensity (non-myeloablative) allogeneic HSCT may be just as effective in treating SAA. Low-dose chemotherapy is used instead of high-dose chemotherapy and TBI. Some smaller studies have indicated that reduced intensity preparative regimens using Fludarabine and Cyclophosphamide allowed engraftment in the matched sibling donor setting with an acceptable level of toxic side effects in subjects with a variety of hematologic cancers. Additional studies that followed showed that a reduced intensity preparative regimen that included fludarabine, cyclophosphamide and antithymocyte globulin, allowed engraftment of donor stem cells in subjects with SAA with acceptable engraftment rates and a decrease in the severity of GVHD.

This study is designed to evaluate the effectiveness of allogeneic transplant after a reduced-intensity preparative regimen, to evaluate survival, and to evaluate the side effects including GVHD of this treatment. Patients will be in the study for two years for treatment and active monitoring. All patients will be followed until death.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 21 years old or younger
  • Male or female recipients must have histopathologically confirmed diagnosis of severe aplastic anemia. Diagnostic Criteria for Server Aplastic Anemia will be based on the definitions set forth by the international Aplastic Anemia Study Group
  • At least two of the following:

Absolute neutrophil count <0.5 x 109/L Platelet count <20 x 109 /L Anemia with corrected reticulocyte count <1%

AND

  • Bone marrow cellularity <25%, or bone marrow cellularity <50% with fewer than 30% hematopoietic cell
  • Availability of an HLA identical sibling

Exclusion Criteria:

  • Active and uncontrolled infection
  • HIV-1 infection
  • Pregnancy or breastfeeding.
  • DLCO <40% predicted
  • Left Ventricular Ejection Fraction < 40%
  • Performance scale Karnofsky <=40% or Lansky<=40% for patients <16 years old
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01129323

Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Anna Pawlowska, MD City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01129323     History of Changes
Other Study ID Numbers: 07081
Study First Received: April 21, 2010
Last Updated: March 23, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
Anemia, Severe, Aplastic, Reduced-Intensity, Allogeneic, Stem, Cell, Transplantation

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Cyclophosphamide
Fludarabine phosphate
Fludarabine
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
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on September 18, 2014