Zoledronic Acid in Combination With Interleukin-2 to Expand Vγ9Vδ2 T Cells After T-replete Haplo-identical Allotransplant

NCT ID: NCT03862833

Last Updated: 2023-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-07
• Study Completion Date: 2023-08-29

Brief Summary

Patients receiving haplo-SCT are at high-risk of relapse. Vγ9Vδ2 T cells exhibit is a well-known population able to exert cytotoxicity toward a large range of tumor in vitro or in vivo. Activating and expanding Vγ9Vδ2 T cells early after haplo-SCT by using a combination of Zoledronic acid and low-dose interleukine (IL) -2 may be of benefit for patients by reducing incidence of relapse. The optimal dose of IL-2 to use remains to be determined.

This will be a Phase 1 3+3 escalation study. Three to 15 patients are planned. It will be proposed to Patients who refuse to participate to have samples collected until day +70 to study immune and gamma/delta T cells reconstitutions after haplo-transplant.

Detailed Description

Zoledronic acid will be administered as a single dose according to marketing and regulatory authorization at the dose of 4 mg over 15 min intravenously at day+15 post-transplant. Zoledronic acid infusion must be stopped in case of grade 3/4 adverse events during infusion.

IL-2 will be administered at a unique low-dose level 5 days per week for 4 consecutive weeks from Monday to Friday subcutaneously . IL-2 has already marketing authorization for various indications.

Three IL2 levels will be tested:

Level 1: 2 millions UI/Infusion Level 2: 4 millions UI/Infusion Level 3: 6 millions UI/Infusion Zoledronic acid and IL2 have to start at day+15 if it is a Monday or the first Monday following day+15 in order to avoid administration on week-end.

Conditions

Hematopoietic Stem Cell Transplantation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

experimental group

Zoledronic acid and IL-2 Zoledronic acid: 4 mg

Three IL2 levels will be tested:

Level 1: 2 millions UI/Infusion Level 2: 4 millions UI/Infusion Level 3: 6 millions UI/Infusion

Group Type: EXPERIMENTAL

IL2

Intervention Type: DRUG

Three IL2 levels will be tested:

Level 1: 2 millions UI/Infusion Level 2: 4 millions UI/Infusion Level 3: 6 millions UI/Infusion 4 weeks, 5 days per week from day + 15 post graft to day + 40

Zoledronic Acid

Intervention Type: DRUG

4 mg at day +15 post graft

control group

no experimental treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

IL2

Three IL2 levels will be tested:

Level 1: 2 millions UI/Infusion Level 2: 4 millions UI/Infusion Level 3: 6 millions UI/Infusion 4 weeks, 5 days per week from day + 15 post graft to day + 40

Intervention Type: DRUG

Zoledronic Acid

4 mg at day +15 post graft

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age: 18-70 years old
• Patients with a hematological disease eligible for a haplo-SCT using the Baltimore regimen as conditioning regimen (Luznik, BBMT, 2008) (See 5.1.2)
• Patients with no HLA matched sibling or unrelated donors
• ECOG <=2
• Signed informed consent
• Patient affiliated to or beneficiary of the National Health Service
• Patients previously transplanted are eligible to the study

Exclusion Criteria

• Patients with a HLA matched sibling or unrelated donor
• Active uncontrolled infections
• HIV positive, active Hepatitis B or C
• Childbearing or child-breastfeading women
• Women or men without effective contraceptive barrier if needed
• Left ventricular ejection fraction < 50% with no previous severe cardiopathy
• Respiratory insufficiency defined as DLCO <40% of the corrected value
• Creatinine clearance <50 ml/min
• Serum bilirubin >2.5 or transaminases >5 fold of normal value except if due to the hematological disease
• Previous or concurrent second malignancy except for adequately treated basal cell carcinoma of the skin, curatively treated in situ carcinoma of the cervix, curatively treated solid cancer, with no evidence of disease for at least 2 years
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Participation at the same time in another study in which investigational drugs are used
• Absence of written informed consent
• Contra-indication to Zoledronic acid: known hypersensitivity to Zoledronic acid or other bisphosphonate or Zoledronic acid formulation (excipients)
• Recent or programmed dental care
• Contra-indication to IL-2: known hypersensitivity to IL-2 or IL-2 formulation (excipients)
• No previous ou current use of zoledronic acid

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

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Nantes Uh

Nantes, , France

Countries

France

References

Jullien M, Guillaume T, Le Bourgeois A, Peterlin P, Garnier A, Eveillard M, Le Bris Y, Bouzy S, Tessoulin B, Gastinne T, Dubruille V, Touzeau C, Mahe B, Blin N, Lok A, Vantyghem S, Sortais C, Antier C, Moreau P, Scotet E, Bene MC, Chevallier P. Phase I study of zoledronic acid combined with escalated doses of interleukine-2 for early in vivo generation of Vgamma9Vdelta2 T-cells after haploidentical stem cell transplant with posttransplant cyclophosphamide. Am J Hematol. 2024 Mar;99(3):350-359. doi: 10.1002/ajh.27191. Epub 2024 Jan 2.

Reference Type: DERIVED

PMID: 38165016 (View on PubMed)

Other Identifiers

RC18_0419

Identifier Type: -

Identifier Source: org_study_id