Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant for Treatment of High-risk Hematologic Disorders

Hematologic Disorders Clinical Trial

Official title:

Safety and Efficacy of Miltenyi CliniMACS® CD34 Reagent System for Transplant Protocol Utilizing Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant for Treatment of High-risk Hematologic Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03093844
• Other study ID #: 16-1672.cc
• Status: Recruiting
• Phase: N/A
• Start date: October 12, 2017
• Est. completion date: February 10, 2027

Study information

• Verified date: February 2024
• Source: University of Colorado, Denver
• Contact: Derek Schatz
• Phone: 720-848-0628
• Email: derek.schatz[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study to evaluate the safety and efficacy of Miltenyi CliniMACS® CD34 Reagent System to promote engraftment of haploidentical CD34+ selected cells combined with single unit umbilical cord blood transplant for treatment of high-risk hematologic disorders.

Description:

In this clinical protocol, the CliniMACS® CD34 Reagent System will be used for processing hematopoietic progenitor cells collected by apheresis (HPC, Apheresis) from an allogeneic, HLA-haploidentical, related donor to obtain a CD34+ cell-enriched population for hematopoietic reconstitution. The haploidentical donor will be mobilized by G-CSF and undergo one apheresis to collect CD34+ stem cells. The products will be cryopreserved until the time of transplantation. Recipients with hematologic disorders who require transplant will receive a standard conditioning regimen and will receive an allograft on day 0 containing donor CD34+ cells that have been positively selected and T-cell depleted following G-CSF mobilization combined with a single UCB unit.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: February 10, 2027
• Est. primary completion date: February 10, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria - Recipient

• Ages 18-80 years inclusive

• Diagnosed with high risk hematologic disorders warranting stem cell transplant per institutional standard of care

• Lack HLA-identical related donor

• Availability of at least one HLA- haploidentical (i.e. => 5/10 and <= 8/10 HLA match) related donor (HLA-A, B, C, DR, and DQ loci) who is available to donate CD34+ cells.

• Availability of at least one 4/6 HLA-matched (HLA-A, B, and DR loci) cord blood unit from the National Marrow Donor Program (NMDP). The cord blood unit must contain a minimum TNC (prior to thawing) of at least 2x107 cells per kilogram of recipient body weight

• Ability to comprehend the nature of the treatment 6.2. Exclusion Criteria - Recipient (any of the following)

• HLA identical (6/6) related donor available and readily accessible at time of transplantation evaluation

• Any patient not meeting institutional standard guidelines for transplant eligibility

Related Conditions & MeSH terms

• Hematologic Diseases
• Hematologic Disorders

Intervention

Device:
• Miltenyi CliniMACS® CD34 Reagent System
Miltenyi CliniMACS® CD34 Reagent System will be used to prepare CD34+ enriched/T-cell depleted cells from haploidentical mobilized peripheral blood.

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

References & Publications (4)

Kwon M, Bautista G, Balsalobre P, Sanchez-Ortega I, Serrano D, Anguita J, Buno I, Fores R, Regidor C, Garcia Marco JA, Vilches C, de Pablo R, Fernandez MN, Gayoso J, Duarte R, Diez-Martin JL, Cabrera R. Haplo-cord transplantation using CD34+ cells from a third-party donor to speed engraftment in high-risk patients with hematologic disorders. Biol Blood Marrow Transplant. 2014 Dec;20(12):2015-22. doi: 10.1016/j.bbmt.2014.08.024. Epub 2014 Sep 22. — View Citation

Magro E, Regidor C, Cabrera R, Sanjuan I, Fores R, Garcia-Marco JA, Ruiz E, Gil S, Bautista G, Millan I, Madrigal A, Fernandez MN. Early hematopoietic recovery after single unit unrelated cord blood transplantation in adults supported by co-infusion of mobilized stem cells from a third party donor. Haematologica. 2006 May;91(5):640-8. — View Citation

van Besien K, Childs R. Haploidentical cord transplantation-The best of both worlds. Semin Hematol. 2016 Oct;53(4):257-266. doi: 10.1053/j.seminhematol.2016.07.004. Epub 2016 Jul 25. — View Citation

van Besien K, Koshy N, Gergis U, Mayer S, Cushing M, Rennert H, Reich-Slotky R, Mark T, Pearse R, Rossi A, Phillips A, Vasovic L, Ferrante R, Hsu YM, Shore T. Cord blood chimerism and relapse after haplo-cord transplantation. Leuk Lymphoma. 2017 Feb;58(2):288-297. doi: 10.1080/10428194.2016.1190970. Epub 2016 Jun 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of patients with treatment-related serious adverse event rate (TRSAE)	Safety will be monitored continuously with a stopping rule for toxicity based on the treatment-related serious adverse event rate (TRSAE), defined by failure of Miltenyi CliniMACS® CD34 Reagent System to select CD34+ cells, and/or failure to engraft that is higher than historical control (<10% for hematologic malignancies and 34% for severe aplastic anemia).	42 days
Primary	The number of patients with successful engraftment	Failure defined as failure of Miltenyi CliniMACS® CD34 Reagent System to select CD34+ cells, and/or failure to engraft by day 22 for patients with hematologic malignancies, and by day 42 for patients with severe aplastic anemia. Assuming a sample size of 50, if there is an engraftment success rate of 75% (or a failure rate of 25%), there would be a resulting 95% confidence interval of 63% to 87% (that is a width of 12% on either side of 75% successful engraftments	42 days