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

NCT00145626 | Completed Phase 2 Results FDA Device

• 2 other identifiers: INFT2NCI-2011-03671
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Stem cell transplantation; Stem cell transplant; Haploidentical transplant

Outcome Measures

Primary Outcomes (1)

• One-year Survival

  The one-year survival of infants with high-risk hematologic malignancies who receive a haploidentical transplant procedure using a total body irradiation (TBI)-excluding conditioning regimen followed by an HLA-nonidentical family donor hematopoietic stem cell (HSC) graft depleted of T cells ex vivo using the CliniMACS CD34+ selection system, with a subsequent infusion of donor NK cells purified ex vivo using the CliniMACS CD3+ depletion and CD56+ enrichment system. The Kaplan-Meier estimate for one-year survival is reported.

  One year after transplant

Secondary Outcomes (15)

• Number of Transplant-Related Adverse Outcomes: Regimen-Related Mortality

  100 days post-transplantation

• Number of Transplant-Related Adverse Outcomes: Engraftment Failure

  100 days post-transplantation

• Number of Transplant-Related Adverse Outcomes: Fatal Acute Graft-Versus Host Disease (GVHD)

  100 days post-transplantation

• Number of Incidences of Chronic GVHD.

  Up to 5 years after transplant

• Factors Affecting One-year Survival: Median Age of Donor at HSCT

  Up to one year after transplant

Study Arms (1)

Study Participants

EXPERIMENTAL

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.

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

Interventions

Chemotherapy and antibodies 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.

Also known as: Cyclophosphamide, Fludarabine, Thiotepa, Melphalan, OKT3

Study Participants

Miltenyi Biotec CliniMACS DEVICE

Stem cell selection device

Study Participants

Allogeneic stem cell transplantation PROCEDURE

Allogeneic natural killer (NK)cell infusion

Also known as: Haploidentical stem cell transplantation, Allogeneic stem cell transplant, Immunotherapy, Mismatched family member donor transplant, NK cell infusions

Study Participants

Eligibility Criteria

• Age: Up to 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Assisi Foundation: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Anemia, Refractory, with Excess of Blasts; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Histiocytosis

Interventions

Drug Therapy; Antibodies; Cyclophosphamide; fludarabine; Thiotepa; Melphalan; Muromonab-CD3; Immunotherapy

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Immunoglobulin G; Immunoglobulin Isotypes; Immunomodulation; Biological Therapy

Limitations and Caveats

The study was limited due to the unavailability of the study drug OKT3 beginning in June 2011. The study was temporarily closed to accrual. Because OKT3 is still unavailable, the study was formally closed to accrual in March 2015.

Results Point of Contact

• Title: Brandon Triplett, MD
• Organization: St. Jude Children's Research Hospital

referralinfo@stjude.org

866-278-5833

Study Officials

• Brandon Triplett, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2005
• First Posted: September 5, 2005
• Study Start: May 1, 2004
• Primary Completion: March 1, 2015
• Study Completion: July 1, 2016
• Last Updated: June 19, 2017
• Results First Posted: December 14, 2015

Record last verified: 2017-05

Locations

US (1)