The primary objective of this protocol is to expand access for patients who lack a fullyHLA (Human leukocyte antigen) matched sibling donor, and who are candidates forallogeneic hematopoietic stem cell transplant (HSCT). These patients have a serious orimmediately life-threatening disease for which HSCT is indicated. These patients are noteligible for other Children's Hospital of Philadelphia Institutional Review Board (IRB)approved protocols that utilize CliniMACs technology for T depletion.
Only 25-30% of patients who may benefit from HSCT have a matched related donor. An
unrelated cord blood may not be available due to size or matching criteria, or if a
reduced intensity regiment is recommended. The risk of severe graft vs. host disease
(GVHD) and other complications is higher with unrelated donors, or partially matched
related donors. At the Children's Hospital of Philadelphia (CHOP) there is extensive
experience using mismatched unrelated donors or partially matched related donors with
complete or partial T depletion to reduce the risk of severe GVHD.
Device: Apha/beta T and CD19+ cell depletion using CliniMACS device
Stem cells will be processed using the CliniMACS device for alpha/beta and CD19+ T cell
depletion. Processing of cells using the CliniMACS will occur in accordance with the
Investigator Brochure and Technical Manual following the laboratory standard operating
procedures (SOPs) and using aseptic technique.
PATIENT AND DONOR ELIGIBILITY
Patients who lack an HLA matched sibling and who are candidates for allogeneic
hematopoietic stem cell transplant (HSCT) but do not meet criteria for current open
institutional protocols using ClinMACs device for β T/CD19+ depletion.
Patients with the following transplantable diseases:
Non-malignant diseases:
- Metabolic storage diseases correctable by HSCT
- Bone marrow failure syndromes
- Immunodeficiencies/immune dysregulation syndromes
- Sickle cell disease or thalassemia
- Other diseases treated with HSCT
Malignant diseases:
- Acute leukemias
- Chronic leukemias
- Lymphomas
- Myelodyplastic syndrome
Organ function criteria:
It is important to note that the conditioning prescribed to the patient will be
determined based on the disease and organ status and will be regimens considered
standard. Appropriate combinations of chemotherapy, immunotherapy and/or radiation will
be determined on an individual basis.
Patient eligibility will be assessed as per our institutional standard operating
procedures:
- Lansky or Karnofsky performance >60
- Renal function: will be determined based on serum creatinine as per our
Institutional SOP
- Hepatic: Transaminases will be assessed as per current institutional SOP
- Cardiac: Cardiac function will be assessed as per institutional SOP
- No active untreated infection
- Signed informed consent
- No fully HLA matched sibling donor available.
- Females of childbearing potential must have negative pregnancy test.
- Subjects with graft failure who require a second HSCT will not need to meet
eligibility criteria again prior to the second transplant. Graft failure is a
medical emergency that requires HSCT
Donor Eligibility Patients must have an identified living donor
- Donor selection will comply with 21 Code of Federal Regulations (CFR) 1271*
- Unrelated donor that meets the matching criteria of the NMDP: Unrelated donors that
may be up to a one antigen mismatch at A, B or DRB1. donor
- Related donor mismatched at one to five antigens (haploidentical)
- Donor suitable for mobilization of peripheral stem cells and apheresis and fulfills
infectious disease criteria as per our institutional SOP, including HIV, Hepatitis B
(HepB), Hepatitis C (HepC) polymerase chain reaction (PCR) negative.
- CHOP bone marrow transplant (BMT) procedures apply for determining donor
eligibility, including donor screening and testing for relevant communicable disease
agents and diseases. Our donor collection program is Foundation for the
Accreditation of Cellular Therapy (FACT) accredited.
- Unrelated donor identified through the National Marrow Donor Program (NMDP) and
fulfills the NMDP criteria for donation. Unrelated donor willing and able to undergo
mobilization of peripheral stem cells and apheresis
- The donors selected for this investigational new drug (IND) will either be unrelated
donors identified through the National Marrow Donor Program (NMDP) or related
donors. Regarding the unrelated donors; NMDP procedures for determining donor
eligibility include donor screening and testing for relevant communicable disease
agents and diseases.
Exclusion criteria:
- Uncontrolled bacterial, viral or fungal infections
- Fully HLA matched sibling donor
- Donor unable to donate peripheral stem cells
- Pregnant Females
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Investigator: Megan Atkinson
Contact: 215-590-2820
cttsbmtintake@chop.edu
Megan Atkinson
215-590-2820
cttsbmtintake@chop.edu
Patricia Hankins, BSN, RN, CCRC
215-590-5168
hankinsp@chop.edu
Tim Olson, MD, PhD, Principal Investigator
Children's Hospital of Philadelphia