CD34+ Cell Enriched and T Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Mismatched Related Donors or Borderline Organ Function

Not Applicable

Completed

Conditions: Malignant Diseases
Non-malignant Diseases

Interventions: Device: CliniMACS CD34+ cell enrichment and T-cell depletion

Registration Number: NCT02162511

Lead Sponsor: Rajni Agarwal

Brief Summary: The purpose of this protocol is to provide access to the CliniMACS® System to hematopoietic cell transplant (HSCT) patients who do not have a matched related donor. The CliniMACS system is currently approved for use in patients who have AML, and a genetically matched sibling donor. Through this protocol, the investigators will be able to offer potentially life-saving transplants to patients who have genetically mis-matched donor, who have no other options for treatment.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3

Inclusion Criteria

Participant age is 0 (newborn) to 35 years-old.
Participant has a disorder affecting the hematopoietic system that are inherited, acquired, or a result from the myeloablative treatment that can benefit from alternative stem cell transplantation according to standard practice guidelines for including patients for transplant.
Participant's medical screening clears s/he for allogeneic transplantation as per current institutional SOP based on standards of foundation for accreditation of cellular therapy and stem cell transplantation (FACT);
Participant must lack a healthy, HLA-identical related or unrelated donor unless s/he has a borderline organ function that will preclude the recipient from receiving a curative therapy due to the need of post-HSCT immunosuppressive therapy.
Participant must have a matched or mismatched-related donor who is:
Able to receive granulocyte colony-stimulating factor (G-CSF) and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter OR agrees on a bone marrow harvest;
Healthy as per donor selection screening (following current SOP based on standards of foundation for accreditation of cellular therapy and stem cell transplantation - FACT);
Willing to participate and sign consent.
Participant or Legal Authorized Representative is able to sign informed consent (and signed assent, if applicable) for transplant.

Exclusion Criteria

Participant does not qualify for an allogeneic transplant due to medical screening, underlying disease, or lack of alternative donors.
Any condition that compromises compliance with the procedures of this protocol, as judged by the principal investigator.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARM B Malignant Non-TBI	CliniMACS CD34+ cell enrichment and T-cell depletion	Malignant diseases chemotherapy based conditioning
ARM A Malignant TBI	CliniMACS CD34+ cell enrichment and T-cell depletion	Malignant diseases Conditioning including total body irradiation and chemotherapy
ARM C Non-malignant	CliniMACS CD34+ cell enrichment and T-cell depletion	Non-malignant diseases Chemotherapy based conditioning

Primary Outcome Measures

Name	Time	Method
Number of Patients With Severe (Grade III/IV) Acute Graft vs Host Disease (GVHD)	Day +100	GVHD is a condition that occurs when donor bone marrow or stem cells attack the recipient.

Secondary Outcome Measures

Name	Time	Method
Immune Recovery (CD4)	up to +1 year post-transplant	The time to CD4 count \>100
Immune Recovery Shown as Phytohemagglutin (PHA)	6 months and 1 year post-transplant	Immune recovery defined as achieving normal levels of PHA (53,000-200,000 CPM)
Length of Time to Engraftment	up to +1 year post-transplant	Absolute neutrophil count (ANC) \>500 for 3 consecutive days and \>80% donor cells in blood.
Number of Patients With Post-transplant Lymphoproliferative Disease (PTLD)	up to +1 year post-transplant	Post-transplant lymphoproliferative disorder (PTLD) is a well-known, life-threatening complication of organ transplantation, predominantly occurring after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT).
Transplant-related Mortality (TRM)	at Day +100 and +1 year post-transplant	Death related to transplant
Number of Participants With Graft Failure	Up to Day +42 after stem cell transplant	Failure of donor stem cells to make neutrophils
Number of Participants Experiencing Post-transplant Infections	up to +1 year post-transplant	Post-transplant infections will be described by incidence and type. Participants may have had more than one type of infection.
Chimerism of Donor Cells	Day +100 post-transplant	The percentage of donor cells for all evaluable (without disease progression) patients
Number of Participants With Immune Recovery (CD4 >200) by Year 1	up to +1 year post-transplant
Number of Patients With Severe Toxicities	up to +1 year post-transplant	Incidence of transplant-related toxicities