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

NCT ID: NCT00145626

Last Updated: 2017-06-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2016-07-31

Brief Summary

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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study Participants

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.

Group Type: EXPERIMENTAL

Chemotherapy and antibodies

Intervention Type: DRUG

Study participants will receive a non-TBI based preparative regimen consisting of Cyclophosphamide, fludarabine, thiotepa, melphalan, and muromonab-CD3 (OKT3) followed by an infusion of a T-lymphocyte depleted haploidentical hematopoietic stem cell graft. Seven days posttransplant, participants will receive an infusion of additional donor derived cells called NK cells.

Miltenyi Biotec CliniMACS

Intervention Type: DEVICE

Stem cell selection device

Allogeneic stem cell transplantation

Intervention Type: PROCEDURE

Allogeneic natural killer (NK)cell infusion

Interventions

Chemotherapy and antibodies

Study participants will receive a non-TBI based preparative regimen consisting of Cyclophosphamide, fludarabine, thiotepa, melphalan, and muromonab-CD3 (OKT3) followed by an infusion of a T-lymphocyte depleted haploidentical hematopoietic stem cell graft. Seven days posttransplant, participants will receive an infusion of additional donor derived cells called NK cells.

Intervention Type: DRUG

Miltenyi Biotec CliniMACS

Stem cell selection device

Intervention Type: DEVICE

Allogeneic stem cell transplantation

Allogeneic natural killer (NK)cell infusion

Intervention Type: PROCEDURE

Other Intervention Names

Cyclophosphamide; Fludarabine; Thiotepa; Melphalan; OKT3; Haploidentical stem cell transplantation; Allogeneic stem cell transplant; Immunotherapy; Mismatched family member donor transplant; NK cell infusions

Eligibility 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

• 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

• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assisi Foundation

OTHER

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brandon Triplett, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

NCI-2011-03671

Identifier Type: REGISTRY

Identifier Source: secondary_id

INFT2

Identifier Type: -

Identifier Source: org_study_id