Expanded Access Protocol (EAP) Using the CliniMACS® Device for Pediatric Haplocompatible Donor Stem Cell Transplant

This is an expanded access trial for Acute Lymphoblastic Leukemia focused on measuring T cell depleted, Matched unrelated donors, Haplocompatible donors, Graft vs Host Disease, Hemoglobinopathies, Leukemia, Leukemia, Lymphoid, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myeloid, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma, Myelodysplastic Syndromes, Preleukemia, Osteopetrosis, Pancytopenia, Immune System Diseases, Hematologic Diseases, Genetic Diseases, Inborn, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Myeloproliferative Disorders, Bone Marrow Diseases, Precancerous Conditions, Osteosclerosis, Osteochondrodysplasias, Bone Diseases, Developmental, Bone Diseases, Musculoskeletal Diseases, Severe acquired and congenital cytopenias, White and red blood cell abnormalities Read More

Inclusion Criteria:

• >2 months - 30 years
• Patient must have a malignant or non-malignant disease that can benefit from alternative stem cell transplantation according to standard practice guidelines for including patients for transplant as outlined in UCSF Pediatric Bone Marrow Transplant (BMT) Standard Operating Procedure (SOP) #206.04. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias, white and red blood cell abnormalities, inborn errors of metabolism and immunodeficiencies. Patient with Fanconi's Anemia will be eligible regardless of match with donor.
• Patients with acute leukemia (AML excepted) or lymphoma must be in remission at the time of transplant.
• Patients must lack a healthy human leukocyte antigen (HLA)-identical related donor.
• Recipient or authorized guardian must sign informed consent for this study.
• If recipient is female and of child-bearing age, negative pregnancy test.

• Patient must have a healthy, willing mismatched related or an unrelated donor who is:

  • Able to receive Granulocyte colony-stimulating factor (G-CSF) +/- Plerixafor and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter,
  • For Related donor: sibling, half-sibling, parent, cousin, aunt, uncle or grandparent will all be considered eligible.
  • For Related donor: HLA antigen genotypic match ≥ 4/8 and ≤ 7/8 (haplocompatible).
  • For unrelated donor: 6/8 or 7/8 HLA antigen match (if two mismatches, they must be at different loci).
  • Complete medical history, physical and screening for infectious diseases that are acceptable for donation.
  • If donor is female and of child-bearing age, negative pregnancy test.
  • Absence of anti-HLA antibodies in recipient directed against donor antigens.
  • Donor must be willing to sign informed consent for this study. If donor is < 18 years of age, donor must be willing to give assent and parents willing to sign informed consent.

• Be suitable for an autologous gene-modified transplant:

  • Using either bone marrow or cytokine-mobilized peripheral blood stem cells (PBSC).
  • Patient or authorized guardian must sign informed consent for this study.
• For unrelated donors: Per New Algorithm, Jan. 14, 2016, effective immediately, National Marrow Donor Program (NMDP) "Be The Match" is adopting a revised algorithm for determining if a donor is a research subject on their recipient's research protocol: The NMDP will inform the donor of the activities and the use of donor's apheresis product to be used in this study and obtain written consent from the donor. Transplant centers are sent documentation of the donor consent to participate in the research support activities. (The revised algorithm can be found on the "Be the Match Clinical Network")

• Criteria to consider when choosing among related haplo donors:

  • CMV positive donor is preferred over other factors. CMV negative donor can be used only if recipient is CMV negative.
  • HLA disparity i.e. 2 Ag mismatch preferred over 3 Ag mismatch; Drβ1 match preferred over class I match; HLA-C matched preferred over A and B match.
  • killer immunoglobulin-like receptor (KIR) mismatch in GVH direction is preferred for patients with malignant disorders
  • ABO compatibility
• Age ≥ 2 months

Exclusion Criteria:

• Patient with an anticipated life expectancy of < 1 month
• Active infectious hepatitis or cytomegalovirus (CMV) disease (organ involvement)
• Human immunodeficiency virus (HIV) or Human T-lymphotropic virus (HTLV-I/II) infection
• Cardiac ejection fraction < 45%; can be lower if patient is not in clinical cardiac failure and a reduced intensity conditioning regimen is used.
• Creatinine clearance <60 ml/min/1.72 m2; can be lower if a reduced intensity conditioning regimen is used.
• Pulmonary diffusion capacity (corrected for hemoglobin), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) <60% of predicted or oxygen saturation (O2 sat) > 94% on room air if unable to perform pulmonary function tests (PFTs); can be lower if a reduced intensity conditioning regimen is used.
• Serum alanine aminotransferase (ALT) > 5 x upper limit of normal (can be up to 10x upper limit of normal if a reduced intensity conditioning regimen is used) or bilirubin > 2.
• Performance score (Lansky/Karnofsky) < 50
• Any condition that compromises compliance with the procedures of this protocol, as judged by the principal investigator.