Study Evaluating the Safety and the Efficacy of Human T Lymphoid Progenitor (HTLP) Injection to Accelerate Immune Reconstitution After Umbilical Cord Blood (UCB) Transplantation in Adult Patients With Hematologic Malignancies (HTLP-ONCO)

NCT ID: NCT04707300

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-16
• Study Completion Date: 2028-08-31

Brief Summary

This is an open-labelled and non-controlled Phase I/II clinical trial, evaluating the safety and the efficacy of Human T Lymphoid Progenitor (HTLP) injection to accelerate immune reconstitution after umbilical cord blood (UCB) transplantation in adult patients with hematologic malignancies. The dose limiting toxicity of HTLP injection will be evaluated using a model-based design.

Detailed Description

Allogeneic bone marrow transplantation (AlloSCT) is the treatment of choice for high- risk acute myeloid leukemias in complete first remission after induction therapy and other high-risk hematological malignancies. Umbilical cord blood grafts are frequently used for patients lacking an HLA- matched family donor (Matched-sibling donor, MSD) as well as in the absence of an appropriate unrelated donor (10/10 MUD). As any HSCT, UCB transplantations are associated with the risk of acute and chronic GVHD, post- transplant immunodeficiency with increased risk of infections as well as relapse. Especially the risk of infection and therefore non- relapse mortality (NRM) or transplant- related mortality (TRM) is significantly higher in UCB transplantations as compared to MSD or 10/10 MUD transplantations. All of these risks have been linked to a significant delay in immune reconstitution including various immune cell populations like CD4 and CD8 T cells, Treg, NK, iNKT, pDC and others.

The investigators therefore make the hypothesis that if T-cell-mediated immunity was rapidly generated after a partially HLA-compatible UCB transplantation will reduce the risk of infection and to prevent relapse without increasing the risk of GVHD.

Conditions

Hematologic Malignancy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Human T Lymphoid Progenitor (HTLP) injection

HTLP cellular product obtained after 7 days of culture of immune-selected CB

Group Type: EXPERIMENTAL

Human T Lymphoid Progenitor (HTLP) injection

Intervention Type: DRUG

The HTLP cell suspension will be injected intravenously at the time of UCB HSCT on D0

Interventions

Human T Lymphoid Progenitor (HTLP) injection

The HTLP cell suspension will be injected intravenously at the time of UCB HSCT on D0

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult patients (≥ 18 years old and <66 years old) at the time of inclusion and eligible for an allogeneic stem cells transplantation and fit to receive the specified conditioning regimen
• Patients with hematologic malignancies
• Absence of a matched - related sibling donor (MSD) or a matched unrelated donor (MUD) 10/10
• Presence of two UCB units with the following criteria*: HLA- matched 4/8, 5/8, 6/8, 7/8 or 8/8 for HLA- A, -B, -C and DRB1 loci

AND

• Presence of at least one UCB unit with the following criteria*: ≥ 3 x 10e7 TNC/kg or ≥ 1.5 10e5 CD34+/kg pre- freezing

• For the UCB taken into HTLP culture, the CD34+ content does not need to meet the above cellularity criteria, as expansion during HTLP culture has been proven to ensure the appropriate number of CD7+ needed for each dose.

The non- cultured UCB will be chosen to have a higher CD34+ cell content in order to enable long- term hematopoietic engraftment

• Absence of Donor Specific Antibodies (DSA) with a MFI > 5000
• Patient affiliated to social security
• Written, informed consent of the patient

Exclusion Criteria

• Any of the standard contraindications to allogeneic transplant
• Left ventricular ejection fraction <50%
• Abnormal biochemistry results (ALT/AST>10xULN, total bilirubin>2.5xULN, creatinin clearance <60ml/min)
• Inability to understand and provide informed consent
• Concomitant infectious disease: HTLV-I, HIV-I or HIV-II
• Pregnancy or breastfeeding for women of childbearing potential
• Patients with progressive hematologic malignancies
• Previous participation within one month before inclusion in another protocol in which drugs may influence immune reconstitution of bone marrow transplantation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 66 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olivier HERMINE, PhD & MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Elisa MAGRIN, MD

Role: STUDY_DIRECTOR

Département de Biothérapie : Hôpital Necker Enfants malades

Locations

Hôpital Saint Louis

Paris, , France

Site Status: RECRUITING

Service d'Hématologie et thérapie cellulaire / CHU of Bordeaux

Pessac, , France

Site Status: RECRUITING

IUCT Oncopole Toulouse

Toulouse, , France

Site Status: RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status: NOT_YET_RECRUITING

Hematology department / Necker Children's Hospital

Paris, Île-de-France Region, France

Site Status: RECRUITING

Countries

France

Central Contacts

Olivier HERMINE, PhD & MD

Role: CONTACT

olivier.hermine@aphp.fr

+33 144495282

Nelly Briand, PhD

Role: CONTACT

nelly.briand@aphp.fr

01 44 38 18 62 ext. +33

Facility Contacts

Nicolas BOISSEL, MD, PhD

Role: primary

nicolas.boissel@aphp.fr

+33 1 42 49 96 43

Edouard FORCADE, PhD & MD

Role: primary

edouard.forcade@chu-bordeaux.fr

Anne HUYNH, PhD, MD

Role: primary

huynh.anne@iuct-oncopole.fr

05 31 15 71 91

Jean-Henri BOURHIS, PhD MD

Role: primary

jean-henri.bourhuis@gustaveroussy.fr

+33 1 42 11 53 82

Olivier HERMINE, PhD & MD

Role: primary

olivier.hermine@aphp.fr

+33 144495282

Felipe SUAREZ, PhD & MD

Role: backup

felipe.suarez@aphp.fr

Other Identifiers

2019-004883-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP191116

Identifier Type: -

Identifier Source: org_study_id