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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00578292
Recruitment Status : Terminated (Stem cell transplant was determined SOC for this disease (study is not relevant))
First Posted : December 21, 2007
Results First Posted : May 1, 2020
Last Update Posted : May 1, 2020
Information provided by (Responsible Party):
Tami D. John, Baylor College of Medicine

Brief Summary:

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 or disease Intervention/treatment Phase
Thalassemia Drug: Busulfan Drug: Fludarabine Drug: Campath 1H Drug: Cyclophosphamide Drug: MESNA Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : February 2004
Actual Primary Completion Date : May 2016
Actual Study Completion Date : May 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Bone Marrow or Stem Cell Infusion

Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H

Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0.

Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/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
50 mg/kg Days -5 through -2
Other Name: Cytoxan

10 mg/kg x 5 Days -5 through -2
Other Name: Mesnex

Primary Outcome Measures :
  1. Engraftment Rate After Transplant [ Time Frame: up to 30 days ]
    Engraftment is defined as an absolute neutrophil count (ANC) >500/microL x 3 days.

  2. Number of Participants With Stable Mixed Hematopoietic Chimerism (HC) [ Time Frame: 1 year post-transplant ]
    Stable hematopoietic chimerism is defined as having 50-99 percent of donor cells.

  3. Number of Participants With Transient Mixed Hematopoietic Chimerism (HC) [ Time Frame: 1 year post-transplant ]
    Transient mixed hematopoietic chimerism is defined as any mixed chimerism return to 100 percent donor.

  4. Number of Participants With Infectious Complications [ Time Frame: up to day 100 ]
    All AEs and SAEs (including infections) will be collected for evaluation of infectious complications.

  5. Hematopoietic Reconstitution [ Time Frame: 1 year post-transplant ]
    Hematopoietic: defined as transfusion independence.

  6. Immune Reconstitution [ Time Frame: 1 year post-transplant ]
    Immune reconstitution: defined as absolute lymphocyte count (ALC) >1000x10e3/microL

  7. Number of Participants With ACUTE GVHD [ Time Frame: Assessed weekly from Day 0 to day 100 ]
    Acute GVHD is graded by the method of Przepiorka D. et al, which evaluates skin involvement, lower and upper GI, and liver function (bilirubin), each being graded in stages from 0 to 4, where 0 means no acute GVHD, and 4 is the highest stage of acute GVHD

  8. Number of Participants With CHRONIC GVHD [ Time Frame: Assessed monthly from month 3 to month 12 ]
    Chronic GVHD is graded by NIH guidelines for chronic GVHD, which evaluates skin, joints, oral, ocular, hepatic, esophagus, GI, respiratory, platelet, and musculoskeletal involvement, in stages from 0 to 3 where 0 means no chronic GVHD, and 3 is the highest stage of chronic GVHD.

  9. Event-free Survival [ Time Frame: up to 2 years post transplant ]
    Event-free survival is calculated from the date of transplant to the date of graft failure, disease recurrence or death from any cause.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 64 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00578292

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United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
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Principal Investigator: Tami John, MD Baylor College of Medicine - Texas Children's Hospital
Study Director: Tami John, MD Baylor College of Medicine - Texas Children's Hospital
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Responsible Party: Tami D. John, Assistant Professor, Hematology/Oncology, Baylor College of Medicine Identifier: NCT00578292    
Other Study ID Numbers: THALLO (H-14539)
H-14539 ( Other Identifier: Baylor College of Medicine IRB )
First Posted: December 21, 2007    Key Record Dates
Results First Posted: May 1, 2020
Last Update Posted: May 1, 2020
Last Verified: April 2020
Keywords provided by Tami D. John, Baylor College of Medicine:
homozygous b0/+-thalassemia
severe variants of b0/+-thalassemia
iron chelating agents
transfusion-dependent homozygous
Additional relevant MeSH terms:
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Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological