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

An Expanded Access Study Using the CliniMACS System to Offer Therapeutic Manipulated Grafts That Are CD34 Cell Enriched and T Cell Depleted for Allogeneic Stem Cell Recipients With Mismatched Related Donors or Borderline Organ Function

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.

Study Overview

• Status: Completed
• Conditions: Malignant Diseases; Non-malignant Diseases
• Intervention / Treatment: Device: CliniMACS CD34+ cell enrichment and T-cell depletion

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 35 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM A Malignant TBI; Malignant diseases Conditioning including total body irradiation and chemotherapy	Device: CliniMACS CD34+ cell enrichment and T-cell depletion
Experimental: ARM B Malignant Non-TBI; Malignant diseases chemotherapy based conditioning	Device: CliniMACS CD34+ cell enrichment and T-cell depletion
Experimental: ARM C Non-malignant; Non-malignant diseases Chemotherapy based conditioning	Device: CliniMACS CD34+ cell enrichment and T-cell depletion

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rajni Agarwal
• Investigators: Principal Investigator: Rajni Agarwal, MD, Stanford University

Publications and helpful links

Helpful Links

• Stanford Stem Cell Transplantation website

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: June 10, 2014
• First Submitted That Met QC Criteria: June 11, 2014
• First Posted (Estimated): June 12, 2014

Study Record Updates

• Last Update Posted (Actual): June 26, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Stem cell transplant; Haplocompatible; Borderline organ function; Alternative donor stem cell transplant
• Other Study ID Numbers: 28663

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes