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)

• Status: Recruiting
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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

• High risk AML in CR1 (with t(6;9), t(v; 11q23), t(9;22), Inv(3), t(3;3), abnormalities of 3q, monosomy 5, 7, 17, complex caryotype, monosomal caryotype, FLT3-ITD (Ratio ≥O.5) without NPM1 mutations) OR

• AML with any adverse genetic abnormality, secondary or therapy related AML excluding good risk genetic abnormalities, or any poor risk feature in CR1 OR

• High-risk myelodysplastic syndrome (MDS) according to Revised International Prognostic Scoring System (IPSS-R).

OR

• MRD+ patients after first line chemotherapy OR

• Relapsed AML in CR2 OR

• >=CR2

• Absence of a matched - related sibling donor (MSD) or a matched unrelated donor (MUD) 10/10

• SORROR score compatible with the pre specified conditioning and to discuss with the Principal Investigator

• Presence of two UCB units with the following criteria*: HLA- matched 6/8, 7/8 or 8/8 for HLA- A, -B, -C and DRB1 loci

• Presence of at least one UCB unit with the following criteria*: ≥ 3 x 107 TNC/kg or ≥ 1.5 105 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

• No prior therapy with allogeneic stem cell transplantation

• No treatment with another investigational drug within one month before inclusion

• Patient affiliated to social security

• Written, informed consent of the patient

• Absence of Donor Specific Antibodies (DSA) with a MFI > 5000

Exclusion Criteria:

• Previous allogeneic stem cell transplantation

• 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