Expanded Cord Blood in Patients in Need of an Allogeneic Stem Cell Transplant

NCT02668315 | Completed Phase 1 DMC

• 1 other identifier: UM0128171
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic hematopoietic stem cell transplantation is a life-saving procedure in patients with blood cancers, but only 25% of transplant candidates have a sibling donor. A matched unrelated donor can be found for 60% of patients but this number is lower for non-Caucasians. Cord blood (CB), another source of stem cells, has major advantages over unrelated donors including immediate availability, better permissiveness in immune mismatches between donor and transplant recipient, better availability for non-Caucasians, and less graft versus host disease, a complication frequently seen after transplant which negatively affects quality of life. Unfortunately, the use of CB is still limited in adults because of the small number of stem cells. UM171, a molecule with hematopoietic stem cell expansion properties, has been shown to increase cord blood stem cells 13 fold. In this trial, Investigators will use UM171 treated CB in patients who need a transplant but lack an acceptable donor.This protocol seeks to test the safety of CB cells expanded with UM171, and to determine the kinetics of engraftment as well as the minimal cord blood unit cell dose that when expanded achieves prompt engraftment.

Conditions

Hematologic Malignancy

Outcome Measures

Primary Outcomes (1)

• Monitoring adverse events, toxicities and medical evolution

  To identify unexpected toxicities associated with transplantation using cord blood cells expanded with UM171/fed-batch culture system by means of history, physical examination and laboratory evaluation. All adverse events will be evaluated for duration, intensity, and causal relationship with the study medication and followed to the end of the study or until resolution.

  up to 36 months post transplant

Secondary Outcomes (15)

• Feasibility of cord blood expansion using UM171 (transplant success)

  18 months

• Kinetics of hematopoietic recovery

  42 days post transplant

• Minimal cord blood cell dose that when expanded achieves prompt engraftment

  up to 12 months

• Correlation between neutrophil and platelet engraftment and CD34+ and CD34+CD45RA- dose

  42 days post transplant

• Incidence of primary and late graft failure

  42 days post transplant

Study Arms (3)

Cohort 1

EXPERIMENTAL

Intervention name: Transplantation of cord blood expanded with UM171 Prethaw CB cell count prior to manipulation: CD34+ cell count 1.0-4.9 x 10E5/kg and TNC superior or equal to 2.0 x 10E7/kg

Biological: Transplantation of cord blood expanded with UM171

Cohort 2

EXPERIMENTAL

Intervention name: Transplantation of cord blood expanded with UM171 Prethaw CB cell count prior to manipulation: CD34+ cell count 0.5-4.9 x 10E5/kg and TNC superior or equal to 1.5 x 10E7/kg

Biological: Transplantation of cord blood expanded with UM171

Cohort 3

EXPERIMENTAL

Intervention name: Transplantation of cord blood expanded with UM171 Prethaw CB cell count prior to manipulation: CD34+ cell count 0.25-4.9 x 10E5/kg and TNC superior or equal to 1.25 x 10E7/kg

Biological: Transplantation of cord blood expanded with UM171

Interventions

Transplantation of cord blood expanded with UM171 BIOLOGICAL

Myeloablative or submyeloablative conditioning regimen followed by an expanded cord blood transplant

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 3 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• years old (Pediatric patients will become eligible only after 5 adult patients have been enrolled in the study and received the UM171 expanded product).
• Weight ≥ 12kg
• Underlying hematologic malignancy excluding primary myelofibrosis requiring an unrelated donor allogeneic HSC transplant (as defined by the transplant center) but patient lacks an 8/8 HLA identical donor or disease requires an urgent transplant and cannot wait the required time to identify an unrelated donor.
• Availability of at least 3 cord bloods with HLA match ≥ 4/6 and ≥4/8 and meeting the following requirements:
• CB to be expanded: CD34+ cell count 1.0-4.9 x 10E5/kg for cohort 1, 0.5-4.9 x 10E5/kg for cohort 2, and 0.25-4.9 x 10E5/kg for cohort 3; nucleated cell count ≥ 2.0 x 10E7/kg for cohort 1, ≥ 1.5 x 10E7/kg for cohort 2, and ≥ 1.25 x 10E7/kg for cohort 3.
• Non expanded cord: TNC count ≥ 2.0 x 10E7/kg with CD34 min of 1 x 10E5/kg or minimum of 1.5 x 10E7 TNC/kg with 1.8 x 10E5 CD34+ cells/kg.
• Back up cord: TNC count ≥ 1.5 x 10E7/kg with CD34 min of 1 x 10E5/kg
• Left ventricular ejection fraction \> 40%.
• Karnofsky score ≥ 70%
• Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and diffusing capacity corrected for hemoglobin (DLCOc) ≥ 50% of predicted
• Bilirubin \< 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis; AST (aspartate aminotransferase) and ALT (alanine aminotransférase) ≤ 2.5 x ULN; alkaline phosphatase ≤ 5 x ULN.
• Measured or estimated creatinine clearance ≥ 60 ml/min/1.73m2.

You may not qualify if:

• Myeloablative transplant within 24 months.
• Uncontrolled infection.
• Presence of a malignancy other than the one for which the UCB transplant is being performed and the expected survival related to the malignancy is estimated to be less than 75% at 5 years.
• HIV positivity.
• Hepatitis B or C infection with measurable viral load.
• Liver cirrhosis.
• Availability of a cord with ≥ 5 x 105/kg CD34+ cells.
• Pregnancy, breastfeeding or unwillingness to use appropriate contraception.
• Participation in a trial with an investigational agent within 30 days prior to entry in the study.
• Patient unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and tests.
• Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome.

Sponsors & Collaborators

• Maisonneuve-Rosemont Hospital: lead
• Canadian Cancer Society (CCS): collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Hopital de l'Enfant-Jesus: collaborator
• Vancouver General Hospital: collaborator
• St. Justine's Hospital: collaborator
• Stem Cell Network: collaborator

Study Sites (1)

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T2M4, Canada

Location

Related Publications (4)

• Liu B, Klatt D, Zhou Y, Manis JP, Sauvageau G, Pellin D, Brendel C, Williams DA. UM171 enhances fitness and engraftment of gene-modified hematopoietic stem cells from patients with sickle cell disease. Blood Adv. 2024 Nov 26;8(22):5885-5895. doi: 10.1182/bloodadvances.2024013932.

  PMID: 39293082 DERIVED

• Cohen S, Bambace N, Ahmad I, Roy J, Tang X, Zhang MJ, Burns L, Barabe F, Bernard L, Delisle JS, Kiss T, Lachance S, Roy DC, Veilleux O, Sauvageau G. Improved outcomes of UM171-expanded cord blood transplantation compared with other graft sources: real-world evidence. Blood Adv. 2023 Oct 10;7(19):5717-5726. doi: 10.1182/bloodadvances.2023010599.

  PMID: 37467030 DERIVED

• Dumont-Lagace M, Li Q, Tanguay M, Chagraoui J, Kientega T, Cardin GB, Brasey A, Trofimov A, Carli C, Ahmad I, Bambace NM, Bernard L, Kiss TL, Roy J, Roy DC, Lemieux S, Perreault C, Rodier F, Dufresne SF, Busque L, Lachance S, Sauvageau G, Cohen S, Delisle JS. UM171-Expanded Cord Blood Transplants Support Robust T Cell Reconstitution with Low Rates of Severe Infections. Transplant Cell Ther. 2021 Jan;27(1):76.e1-76.e9. doi: 10.1016/j.bbmt.2020.09.031. Epub 2020 Oct 3.

  PMID: 33022376 DERIVED

• Cohen S, Roy J, Lachance S, Delisle JS, Marinier A, Busque L, Roy DC, Barabe F, Ahmad I, Bambace N, Bernard L, Kiss T, Bouchard P, Caudrelier P, Landais S, Larochelle F, Chagraoui J, Lehnertz B, Corneau S, Tomellini E, van Kampen JJA, Cornelissen JJ, Dumont-Lagace M, Tanguay M, Li Q, Lemieux S, Zandstra PW, Sauvageau G. Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1-2 safety and feasibility study. Lancet Haematol. 2020 Feb;7(2):e134-e145. doi: 10.1016/S2352-3026(19)30202-9. Epub 2019 Nov 6.

  PMID: 31704264 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Sandra Cohen, MD

  Maisonneuve-Rosemont Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: January 29, 2016
• Study Start: December 16, 2015
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: August 5, 2019

Record last verified: 2019-08

Locations

CA (1)