Wharton Jelly Mesenchymal Stromal Cells as GVHD Prophylaxis

NCT ID: NCT05855707

Last Updated: 2023-05-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-30
• Study Completion Date: 2026-09-30

Brief Summary

Despite progress in chemotherapy, targeted therapy and immunotherapy, allogeneic hematopoietic stem cell transplantation (allo-SCT) is still the only curative procedure for some hematological malignancies. The probability of finding a matched sibling donor (MSD) is estimated under the classical 30%, because of the age of patients and their relatives, and a matched unrelated donor (MUD) can take time to identify. Currently in France, 25% of the allo-SCT are performed with an haplo-identical related donor. The Baltimore group developed an approach using haploidentical related donors, RIC, T-replete bone marrow and post-transplant high dose cyclophosphamide (PTCy) in patients with advanced hematological malignancies. PTCy has shown to eradicate alloreactive donor and host T-cells, activated by respective antigens, thereby reducing the incidence of graft versus host disease (GvHD) but delaying hematopoietic recovery. Therefore, the main source of graft is peripheral blood stem cells (PBSC) mobilized by G-CSF in France. Unfortunately, with PBSC we observe a higher cumulative incidence of GvHD (around 50%) and a higher toxicity-related mortality (TRM), especially for recipients >50 years old. The co-transplantation of Mesenchymal Stem Cells (MSC) at the time of transplantation has previously shown a double interest in GvHD immunomodulation and hematopoiesis support. Pre-clinical studies (in mice) have shown that mesenchymal stromal cells (MSCs) from Wharton's Jelly reduce the incidence of GvHD when the infusions are weekly repeated. We propose a phase I clinical trial to find the maximum tolerated dose (MTD) of a weekly infusion of WJ-MSC administered as GvHD prophylaxis and as a support for a faster hematological reconstitution after haplo-identical allo-SCT.

Conditions

Allogeneic Disease; GVHD,Acute; Graft Failure

Study Design

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

Study Groups

maximum tolerated dose

1. x10e6 WJ-MSC/kg/infusion for 3 weekly infusions 1.5x10e6 WJ-MSC/kg/infusion for 3 weekly infusions

2. x10e6 WJ-MSC/kg/infusion for 3 weekly infusions

Group Type: EXPERIMENTAL

WJ-MSC infusion

Intervention Type: BIOLOGICAL

cellular therapy

Interventions

WJ-MSC infusion

cellular therapy

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• With AML/ALL/SMD/SMP or lymphoid neoplasm requiring allogeneic stem cell transplantation
• In complete response (CR) for AML/ALL or CR,partial response (PR) or non pre-treated for SMD/SMP and lymphoid neoplasm
• Without a HLA matched related donor available and with identification of a haploidentical donor (brother, sister, parents, adult children or cousin)

With usual criteria for HSCT:

• ECOG ≤ 2
• No severe and uncontrolled infection
• Cardiac function compatible with high dose of cyclophosphamide
• Adequate organ function: ASAT and ALAT ≤ 2N, total bilirubin ≤ 1.5N, creatinine clearance ≥30ml/min (except if those abnormalities are linked to the hematological disease)

• Requiring a RIC or non myeloablative conditioning:

(i) >50 years old; (ii) heavily pre-treated; (iii) Comoribidities according to Sorror et al. Blood 2005;106(8):2912-9, notamment HCT/CI≥ 3 (JAMA. 2011 Nov 2;306(17):1874-83).

• With health insurance coverage (bénéficiaire ou ayant droit)
• Understand informed consent or optimal treatment and follow-up
• Contraception methods must be prescribed during all the duration of the research and using effective contraceptive methods during treatment and within 12 months for women of childbearing age and 6 months for men of childbearing age after the last dose of cyclophosphamide

Exclusion Criteria

• History of Cancer in the last 5 years
• Uncontrolled infection: Seropositivity for HIV or HTLV-1 or active hepatitis B or C defined by a positive PCR HBV or HCV and hepatic cytolysis due to HBV
• Uncontrolled coronary insufficiency, recent myocardial infarction <6 month, current manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular ejection fraction <50%
• Pulmonary failure with DLCO<50%
• Addition of immunosuppressant treatment for GVHD prophylaxis (except immunosuppressant allowed per protocol)
• Renal failure with creatinine clearance <50ml / min
• Pregnancy (β-HCG positive) or breast-feeding
• Any debilitating medical or psychiatric illness which would preclude the realization of the SCT or the understanding of the protocol
• Under protection by law (tutorship or curatorship)
• Unwilling or unable to comply with the protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Saint-Louis Hospital, Paris, France

OTHER

Sponsor Role: collaborator

Central Hospital, Nancy, France

OTHER

Sponsor Role: lead

Responsible Party

Maud D'AVENI

MCU-PH

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

2023-504268-40-00

Identifier Type: -

Identifier Source: org_study_id