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| ID | Type | Description | Link |
|---|---|---|---|
| UCSF-01151 | |||
| UCSF-H411-17122-07 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
OBJECTIVES:
OUTLINE: This is a dose-escalation study of donor CD3+ cells and antithymocyte globulin (ATG).
Cohorts of 3-6 patients receive escalating doses of donor CD3+ cells and ATG until the optimum is determined. The optimum dose is defined as the dose at which both engraftment and T-cell recovery occur, without dose-limiting toxicity, in ≥ 5 of 6 patients.
After the completion of study treatment, patients are followed periodically for 5 years and then every 5 years thereafter.
PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single arm of transplant | Experimental | Receiving haplocompatible T cell depleted peripheral blood stem cell transplant |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| anti-thymocyte globulin | Biological |
| ||
| therapeutic allogeneic lymphocytes |
| Measure | Description | Time Frame |
|---|---|---|
| Engraftment at 4 weeks post bone marrow transplantation through 100 days | 100 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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DISEASE CHARACTERISTICS:
Diagnosis of one of the following:
Acute lymphoblastic leukemia in ≥ 2nd remission or delayed remission induction
High-risk myelodysplastic syndromes
Chronic myelogenous leukemia in second chronic phase
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
Congenital marrow aplasias unresponsive to cytokines and transfusion dependent
Inherited immunodeficiency disease involving neutrophils or lymphocytes, including any of the following:
No relapsed disease
Haplocompatible related donor, including parent, cousin, aunt, uncle, grandparent, half-sibling, or sibling (≥ 12 years of age), available
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Morton J. Cowan, MD | University of California, San Francisco | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California | 94115 | United States | ||
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| Biological |
|
| fludarabine phosphate | Drug |
|
| thiotepa | Drug |
|
| allogeneic bone marrow transplantation | Procedure |
|
| allogeneic hematopoietic stem cell transplantation | Procedure |
|
| in vitro-treated peripheral blood stem cell transplantation | Procedure |
|
| total-body irradiation | Radiation |
|
| 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 |
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill |
| Chapel Hill |
| North Carolina |
| 27599-7295 |
| United States |
| ID | Term |
|---|---|
| C535982 | Congenital amegakaryocytic thrombocytopenia |
| D007938 | Leukemia |
| D009190 | Myelodysplastic Syndromes |
| C537592 | Neutropenia, Severe Congenital, Autosomal Recessive 3 |
| D054429 | Leukemia, Myelomonocytic, Juvenile |
| D015466 | Leukemia, Myeloid, Chronic-Phase |
| D000754 | Anemia, Refractory, with Excess of Blasts |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
| D007951 | Leukemia, Myeloid |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D009196 | Myeloproliferative Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000753 | Anemia, Refractory |
| D000740 | Anemia |
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| ID | Term |
|---|---|
| D000961 | Antilymphocyte Serum |
| C042382 | fludarabine phosphate |
| D013852 | Thiotepa |
| D014916 | Whole-Body Irradiation |
| ID | Term |
|---|---|
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D013721 | Triethylenephosphoramide |
| D001388 | Aziridines |
| D001389 | Azirines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
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