Allogeneic Stem Cell Transplantation, Severe Homzygous 0/+Thalassemia or Sever Variants of Beta 0/+ Thalassemia, THALLO

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Baylor College of Medicine
Sponsor:
Collaborator:
Texas Children's Hospital
Information provided by (Responsible Party):
Kathryn Leung, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00578292
First received: December 19, 2007
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

Patients have severe beta-thalassemia or one of the thalassemia variants. Thalassemia is a hereditary disease in which the bone marrow produces abnormal red blood cells that have a shorter life span than normal red blood cells. Because of that, the patient has chronically low red blood cell numbers (anemia) and need regular blood transfusions to help the patient feel better and to help prevent damage to important organs such as the heart. The following treatments are currently available to patients: lifelong blood transfusions and drugs that help remove iron from the body, and long-term antibiotics to prevent infections. These treatments are difficult for patients to take and do not stop the effects of the disease.

Currently, the only treatment that may cure thalassemia is bone marrow or blood stem cell transplantation. Special blood or bone marrow cells from a healthy person might allow the bone marrow to create healthy cells, which will replace the abnormal red blood cells of thalassemia. There is a lot of experience using special blood or bone marrow cells from a healthy brother or sister who is the same HLA (immune) type. For patients who do not have such a donor in the family, an unrelated volunteer donor can be used. It is important for the patient to realize that this kind of transplant can have more problems than a transplant from a brother or sister.

Because we do not know the long-term effects of this treatment and because this type of transplant has not been used often for people with thalassemia, this is a research study. We hope, but cannot promise, that the transplanted marrow/stem cells will produce healthy cells and the patient will no longer have severe thalassemia.


Condition Intervention
Thalassemia
Drug: Busulfan
Drug: Fludarabine
Drug: Campath 1H
Drug: Cyclophosphamide
Drug: MESNA

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Allogeneic Stem Cell Transplantation From Unrelated Donors for Patients With Severe Homozygous Beta 0/+ Thalassemia or Severe Variants of Beta 0/+ Thalassemia

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Evaluate engraftment [ Time Frame: 30 days post transplant ] [ Designated as safety issue: Yes ]
  • To evaluate the occurrence of transient and stable mixed hematopoietic chimerism (HC) after unrelated donor SCT and its effect on the recurrence of clinically measurable thalassemia. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To measure hematopoietic and immune reconstitution and assess the effects on infectious complications. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • toxicities [ Time Frame: +100 days transplant ] [ Designated as safety issue: Yes ]
  • loss of chimerism [ Time Frame: 2 years post transplant ] [ Designated as safety issue: Yes ]
  • GVHD [ Time Frame: 2 years post transplant ] [ Designated as safety issue: Yes ]
  • morbidity and mortality post transplant [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: February 2004
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bone Marrow or Stem Cell Infusion

Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H

Bone Marrow or Stem Cell infusion with premeds to take place on Day 0

Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 108 nucleated cells/kg patient weight or 5 x 106/kg of CD34+cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor.

Drug: Busulfan

4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg

days -9 through -6

Other Name: Myleran
Drug: Fludarabine
30mg/m2 day -5 through day -2
Other Name: Fludara
Drug: Campath 1H
per institutional guidelines days -5 through -2
Other Name: Alemtuzumab
Drug: Cyclophosphamide
50mg/kg days -5 through -2
Other Name: Cytoxan
Drug: MESNA
10mg/kg x 5 days -5 through -2
Other Name: Mesnex

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients with documented diagnosis of severe (transfusion-dependent) homozygous b0/+-thalassemia or severe variants of b0/+-thalassemia requiring chronic transfusion therapy and iron chelating agents who fulfill the following conditions:

  1. Patient does not have an HLA genotype identical donor available and has a 5/6 or 6/6 matched unrelated donor or a 5/6 matched related donor available.
  2. Must be the between 1 and 16 yrs of age (all Pesaro risk groups).
  3. Patients older than 17 yrs of age must be in Pesaro Risk Class 2 or lower (see Appendix B)
  4. Women of childbearing potential must have a negative pregnancy test
  5. Documentation of compliance with iron chelation, absence or presence of hepatomegaly, and presence or absence of hepatic fibrosis prior to transplant (criteria for the Pesaro Risk Classification). This information will be obtained by history, physical exam and interpretation of liver biopsy results.
  6. Documentation of awareness of alternative treatment options.

Exclusion Criteria:

  1. Biopsy-proven chronic active hepatitis or fibrosis with portal bridging
  2. Has previous history of malignancies
  3. Creatinine clearance <35 ml/min/1.73 M2
  4. Severe cardiac dysfunction defined as shortening fraction <25%
  5. HIV infection
  6. Inadequate intellectual capacity to give informed consent (in the case of minors, this criteria must be fulfilled by the legal guardian)
  7. Be pregnant, lactating or unwilling to use appropriate birth control
  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: NCT00578292

Contacts
Contact: Kathryn Suet Wa Leung, MD 832-824-4219 kleung@bcm.edu
Contact: Marlen Dinu 832-824-4881 mxdinu@txch.org

Locations
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Kathryn S. Leung, MD    832-824-4219    ksleung@txch.org   
Contact: Marlen Dinu    832-824-4881    mxdinu@txch.org   
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
Investigators
Principal Investigator: Kathryn Suet Wa Leung, MD Baylor College of Medicine/Texas Children's Hospital
  More Information

No publications provided

Responsible Party: Kathryn Leung, Assistant Professor, Center for Cell and Gene Therapy, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00578292     History of Changes
Other Study ID Numbers: H-14539-THALLO, THALLO
Study First Received: December 19, 2007
Last Updated: April 1, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
transfusion-dependent
homozygous b0/+-thalassemia
severe variants of b0/+-thalassemia
chronic transfusion therapy
iron chelating agents
severe
transfusion-dependent homozygous b0/+-thalassemia or severe variants of b0/+-thalassemia

Additional relevant MeSH terms:
Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Mesna
Busulfan
Cyclophosphamide
Fludarabine monophosphate
Campath 1G
Fludarabine
Alemtuzumab
Iron Chelating Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Chelating Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 20, 2014