Wharton Jelly Mesenchymal Stromal Cells as GVHD Prophylaxis

Graft Failure Clinical Trial

— HAPLO-GEL  

Official title:

Wharton's Jelly Mesenchymal Stromal Cell (WG-MSC) Injections as GVHD Prophylaxis in Hematopoietic Allogeneic Stem Cell Transplantation With an Haplo-identical Donor : a Dose Escalation Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05855707
• Other study ID #: 2023-504268-40-00
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: September 2023
• Est. completion date: September 2026

Study information

• Verified date: May 2023
• Source: Central Hospital, Nancy, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: September 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 (ß-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

Related Conditions & MeSH terms

• Allogeneic Disease
• Graft Failure
• GVHD,Acute

Intervention

Biological:
• WJ-MSC infusion
cellular therapy

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France	Saint-Louis Hospital, Paris, France

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose	The maximum tolerated dose (MTD) will be defined by the highest dose (highest level) where no patient out of 3, or only 1 patient out of 6 presents with dose-limiting toxicity (DLT).; The occurrence, within 7 days following one of the three injections, of any adverse event (AE) reasonably related to the injection of CSM-GW grade 3 to 5 according to the NCI-CTCAE classification version 5.0, or part of the "Important Medical Event list", or having a severity criterion; The maximum tolerated dose (MTD) will be defined by the highest dose (highest level) where no patient out of 3, or only 1 patient out of 6 presents with dose-limiting toxicity (DLT).; The occurrence, within 7 days following one of the three injections, of any adverse event (AE) reasonably related to the injection of CSM-GW grade 3 to 5 according to the NCI-CTCAE classification version 5.0, or part of the "Important Medical Event list", or having a severity criterion	7 days
Secondary	acute and chronic GVHD incidence		12 months
Secondary	toxicity-related mortality (TRM)		12 months
Secondary	relapse incidence (RI)		12 months
Secondary	overall surival (OS)		12 months
Secondary	GvHD and relapse free survival (GRFS)		12 months
Secondary	poor graft function		12 months