HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies

St. Jude Children's Research Hospital

Status and phase: Completed; Phase 2

Conditions: Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Myelodysplasia; Histiocytosis; Acute Myeloid Leukemia

Treatments: Drug: Chemotherapy and antibodies; Device: Miltenyi Biotec CliniMACS; Procedure: Allogeneic stem cell transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT00145626

INFT2

NCI-2011-03671 (Registry Identifier)

Details and patient eligibility

About

Recent studies of conventional chemotherapy for infants with high-risk hematologic malignancies show that the long-term disease-free survival is low. Although blood and marrow stem cell transplantation using an HLA identical sibling has improved the outcome for these children, less than 25% have this donor source available. Another option is haploidentical transplantation using a partially matched family member donor (i.e. parental donor).

Although haploidentical transplantation has proven curative for some patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including infection and graft versus host disease (GVHD). Building on prior institutional trials, this study will provide patients a haploidentical graft depleted of T lymphocytes using the investigational device, CliniMACS selection system. One week after the transplant procedure, patients will also receive an infusion of additional donor derived white blood cells called Natural Killer (NK) cells in an effort to decrease risks for rejection of the graft, disease relapse, and regimen related toxicity. The primary objective of the study is to evaluate 1 year survival in infants with high risk hematologic malignancies who receive this study treatment.

Full description

Secondary objectives for this study include the following:

• To estimate the incidence of three transplant-related adverse outcomes (i.e., regimen-related mortality, engraftment failure, and fatal acute GVHD) in the first 100 days after transplantation.
• To estimate the incidence of chronic graft-versus-host disease.
• To evaluate those factors that affect one-year survival.
• To assess the kinetics of lymphohematopoietic reconstitution.
• To assess the frequency and clinical relevance of minimal residual disease (MRD) before and after transplantation.
• To evaluate the incidence of and risk factors for long-term neurocognitive deficit and organ dysfunction.

Enrollment: 40 patients

Sex: All

Ages: Under 24 months old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Must have one of the following diagnosis:

• AML in remission or relapse (e.g., FAB M7 or biphenotypic leukemia)
• High-risk ALL in first remission (e.g., poor responder to prednisone, Ph+ ALL)
• ALL beyond first remission
• Secondary leukemia
• Primary myelodysplasia (including RAEB, RAEB-T, CMML, JCML, and JMML)
• Chronic myeloid leukemia
• Histiocytoses (including multi-system Langerhans' cell histiocytosis and hemophagocytic lymphohistiocytosis

Inclusion criteria Donor research participants

• HIV negative (date).
• Hepatitis B surface antigen negative (date).
• Hepatitis C antibody negative (date).
• Syphilis negative (date).
• Donor is equal to or greater than 3 on 6 HLA match (date).
• Not pregnant (negative pregnancy test).
• Not lactating.
• At least 18 years of age.

Exclusion Criteria

• Patients greater than 24 months of age at the time of transplant.
• HLA-identical sibling donor is available.
• Cardiac function: shortening fraction <25%.
• Pulse oximetry oxygen saturation <92% on room air.
• Glomerular filtration rate less than 40 ml/min/1.73 m2 (may use Technetium-99 result for GFR).
• Direct bilirubin > 3 mg/dl.
• SGPT > 500 U/L.
• Patients with previous allergy to mouse proteins.
• Patients with previous allergy to rabbit serum products.
• Patients with Down's syndrome

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Study Participants

Experimental group

Description:

Participants who meet the eligibility criteria for this study. Donor cells will be obtained using the Miltenyi Biotec CliniMACS device. Interventions: Chemotherapy and antibodies, allogeneic stem cell transplantation.

Treatment:

Procedure: Allogeneic stem cell transplantation

Device: Miltenyi Biotec CliniMACS

Drug: Chemotherapy and antibodies