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 CliniMACs device for β T/CD19+ depletion. Patients with
matched related donors including matched sibling donors may also be eligible if special
clinical indications are met.
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
Patient Eligibility 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 include agents that are
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:
- Signed informed consent
- Lansky or Karnofsky performance ≥ 60
- Hematologic and Organ Function as per current institutional SOP
- Infectious Evaluation as per current institutional SOP
- Participants of childbearing potential must have a negative pregnancy test as per
institutional SOP
- 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 CFR 1271*
- Unrelated donor that meets the matching criteria of the NMDP with allele matching at
HLA -A, -B, -C, -DRB1, and -DQB1: Unrelated donors may be a 10/10 match, a 9/10
match, or an 8/10 match if one of the mismatches is at DQB1.
- Related donor mismatched at one to five HLA alleles (haploidentical)
- Matched related donor may be considered suitable donors for this protocol if a
peripheral stem cell donation is deemed by the clinical team to be a safer donation
option (if donor is not a suitable candidate for a bone marrow harvest) or if there
is concern that bone marrow harvest would not yield adequate cell doses
Additionally, a matched related donor would be considered suitable for this protocol
if there are safety concerns regarding a patient receiving a standard T cell replete
bone marrow transplant due to individualized GVHD risk or risk related to standard
GVHD prevention medications.
- Donor suitable for mobilization of peripheral stem cells and apheresis and fulfills
infectious disease criteria as per our institutional SOP, including HIV, HepB, HepC
PCR negative.
- We assess donor eligibility as per our Allogenic Donor Evaluation for Eligibility
standard operating procedure. These procedures apply for determining donor
eligibility, including donor screening and testing for relevant communicable disease
agents and diseases. Our donor collection program is FACT accredited.
- Related donors will be consented and enrolled under IRB approved research protocol
for cell collection per IRB 04-004078 CHP 784 Clinical and Research Collection and
Future Research Use of Bone Marrow, Stem Cells or T Cells.
- 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 IDE 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 (fully matched related donors including siblings may
be included in special circumstances)
- 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