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

NCT00578292 | Terminated Results DMC

• 2 other identifiers: THALLO (H-14539)H-14539
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Thalassemia

Keywords

transfusion-dependent; homozygous b0/+-thalassemia; severe variants of b0/+-thalassemia; transfusion; iron chelating agents; severe; transfusion-dependent homozygous

Outcome Measures

Primary Outcomes (9)

• Engraftment Rate After Transplant

  Engraftment is defined as an absolute neutrophil count (ANC) \>500/microL x 3 days.

  up to 30 days

• Number of Participants With Stable Mixed Hematopoietic Chimerism (HC)

  Stable hematopoietic chimerism is defined as having 50-99 percent of donor cells.

  1 year post-transplant

• Number of Participants With Transient Mixed Hematopoietic Chimerism (HC)

  Transient mixed hematopoietic chimerism is defined as any mixed chimerism return to 100 percent donor.

  1 year post-transplant

• Number of Participants With Infectious Complications

  All AEs and SAEs (including infections) will be collected for evaluation of infectious complications.

  up to day 100

• Hematopoietic Reconstitution

  Hematopoietic: defined as transfusion independence.

  1 year post-transplant

• Immune Reconstitution

  Immune reconstitution: defined as absolute lymphocyte count (ALC) \>1000x10e3/microL

  1 year post-transplant

• Number of Participants With ACUTE GVHD

  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

  Assessed weekly from Day 0 to day 100

• Number of Participants With CHRONIC GVHD

  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.

  Assessed monthly from month 3 to month 12

• Event-free Survival

  Event-free survival is calculated from the date of transplant to the date of graft failure, disease recurrence or death from any cause.

  up to 2 years post transplant

Study Arms (1)

Bone Marrow or Stem Cell Infusion

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Campath 1H; Drug: Cyclophosphamide; Drug: MESNA

Interventions

Busulfan DRUG

4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6

Also known as: Myleran

Bone Marrow or Stem Cell Infusion

Fludarabine DRUG

30mg/m2 Day -5 through Day -2

Also known as: Fludara

Bone Marrow or Stem Cell Infusion

Campath 1H DRUG

Per institutional guidelines Days -5 through -2

Also known as: Alemtuzumab

Bone Marrow or Stem Cell Infusion

Cyclophosphamide DRUG

50 mg/kg Days -5 through -2

Also known as: Cytoxan

Bone Marrow or Stem Cell Infusion

MESNA DRUG

10 mg/kg x 5 Days -5 through -2

Also known as: Mesnex

Bone Marrow or Stem Cell Infusion

Eligibility Criteria

• Age: Up to 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Thalassemia; Lymphoma, Follicular

Interventions

Busulfan; fludarabine; fludarabine phosphate; Alemtuzumab; Cyclophosphamide; Mesna

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Sulfhydryl Compounds

Results Point of Contact

• Title: Dr. Tami D. John
• Organization: Baylor College of Medicine/Texas Children's Hospital

tdjohn@texaschildrens.org

832-824-4723

Study Officials

• Tami John, MD

  Baylor College of Medicine - Texas Children's Hospital

  PRINCIPAL INVESTIGATOR

• Tami John, MD

  Baylor College of Medicine - Texas Children's Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Hematology/Oncology

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Study Start: February 1, 2004
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: May 1, 2020
• Results First Posted: May 1, 2020

Record last verified: 2020-04

Locations

US (1)