Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease

NCT00295971 | Completed Phase 1 DMC

• 3 other identifiers: CDR0000462168UCSF-01151UCSF-H411-17122-07
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells and antithymocyte globulin when given together with chemotherapy and total-body irradiation in treating young patients who are undergoing T-cell depleted donor stem cell transplant for myelodysplastic syndrome, leukemia, bone marrow failure syndrome, or severe immunodeficiency disease.

Conditions

Congenital Amegakaryocytic Thrombocytopenia; Leukemia; Myelodysplastic Syndromes; Severe Congenital Neutropenia

Keywords

childhood acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; secondary acute myeloid leukemia; juvenile myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; severe congenital neutropenia; congenital amegakaryocytic thrombocytopenia; childhood chronic myelogenous leukemia; childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• Engraftment at 4 weeks post bone marrow transplantation through 100 days

  100 days

Secondary Outcomes (4)

• Survival assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation

  1 year

• Disease-free survival and infection assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation

  1 year

• Graft-versus-host disease assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation

  2 years

• CD4 count in blood < 100/mm³ at 12 weeks

  12 weeks

Study Arms (1)

Single arm of transplant

EXPERIMENTAL

Receiving haplocompatible T cell depleted peripheral blood stem cell transplant

Biological: anti-thymocyte globulin; Biological: therapeutic allogeneic lymphocytes; Drug: fludarabine phosphate; Drug: thiotepa; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: in vitro-treated peripheral blood stem cell transplantation; Radiation: total-body irradiation

Interventions

anti-thymocyte globulin BIOLOGICAL

Single arm of transplant

therapeutic allogeneic lymphocytes BIOLOGICAL

Single arm of transplant

fludarabine phosphate DRUG

Single arm of transplant

thiotepa DRUG

Single arm of transplant

allogeneic bone marrow transplantation PROCEDURE

Single arm of transplant

allogeneic hematopoietic stem cell transplantation PROCEDURE

Single arm of transplant

in vitro-treated peripheral blood stem cell transplantation PROCEDURE

Single arm of transplant

total-body irradiation RADIATION

Single arm of transplant

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

DISEASE CHARACTERISTICS: * Diagnosis of one of the following: * Acute lymphoblastic leukemia in ≥ 2nd remission or delayed remission induction * High-risk myelodysplastic syndromes * Refractory anemia with excess blasts (RAEB) * RAEB in transformation * Chronic myelogenous leukemia in second chronic phase * No accelerated phase (\> 5% blasts in marrow) * Juvenile myelomonocytic leukemia * Acute nonlymphoblastic leukemia in \> 1st remission or induction failure and \< 30% blasts in marrow * Severe aplastic anemia, defined as absolute neutrophil count \< 500/mm\^3 and platelet and/or red blood cell transfusion dependent * Unresponsive to immunosuppressive therapy * No Fanconi's anemia * Congenital marrow aplasias unresponsive to cytokines and transfusion dependent * Inherited immunodeficiency disease involving neutrophils or lymphocytes, including any of the following: * Chediak-Higashi disease * Wiskott-Aldrich syndrome * Combined immunodeficiency disease (Nezelof's) * Hyper IgM syndrome * No relapsed disease * Haplocompatible related donor, including parent, cousin, aunt, uncle, grandparent, half-sibling, or sibling (≥ 12 years of age), available * 2 or 3 HLA antigen mismatch * At least a 3 HLA antigen genotypic match * No closely matched related or unrelated donor available in sufficient time to do the transplant PATIENT CHARACTERISTICS: * No active hepatitis or cytomegalovirus infection * Cardiac ejection fraction ≥ 30% * Creatinine clearance ≥ 70 mL/min * DLCO ≥ 70% of predicted * No active infection * No HIV positivity PRIOR CONCURRENT THERAPY: * See Disease Characteristics

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

MeSH Terms

Conditions

Congenital amegakaryocytic thrombocytopenia; Leukemia; Myelodysplastic Syndromes; Neutropenia, Severe Congenital, Autosomal Recessive 3; Leukemia, Myelomonocytic, Juvenile; Leukemia, Myeloid, Chronic-Phase; Anemia, Refractory, with Excess of Blasts

Interventions

Antilymphocyte Serum; fludarabine phosphate; Thiotepa; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Refractory; Anemia

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Morton J. Cowan, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 23, 2006
• First Posted: February 24, 2006
• Study Start: April 1, 2005
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: November 12, 2012

Record last verified: 2012-11

Locations

US (2)