Allogeneic Stem Cell Transplantation, Severe Homzygous 0/+Thalassemia or Sever Variants of Beta 0/+ Thalassemia, THALLO
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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 |
- 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 |
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:
- 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.
- Must be the between 1 and 16 yrs of age (all Pesaro risk groups).
- Patients older than 17 yrs of age must be in Pesaro Risk Class 2 or lower (see Appendix B)
- Women of childbearing potential must have a negative pregnancy test
- 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.
- Documentation of awareness of alternative treatment options.
Exclusion Criteria:
- Biopsy-proven chronic active hepatitis or fibrosis with portal bridging
- Has previous history of malignancies
- Creatinine clearance <35 ml/min/1.73 M2
- Severe cardiac dysfunction defined as shortening fraction <25%
- HIV infection
- Inadequate intellectual capacity to give informed consent (in the case of minors, this criteria must be fulfilled by the legal guardian)
- Be pregnant, lactating or unwilling to use appropriate birth control
Contacts and Locations| Contact: Kathryn Suet Wa Leung, MD | 832-824-4219 | kleung@bcm.edu |
| Contact: Marlen Dinu | 832-824-4881 | mxdinu@txch.org |
| 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 | |
| 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: | August 10, 2012 |
| 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 May 23, 2013