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Hematopoietic Stem Cell TransplantationPhase 1HILDEGAZNCT03862833

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

A Phase 1 study testing IL2 and Zoledronic Acid in people with Hematopoietic Stem Cell Transplantation, run by Nantes University Hospital at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Hematopoietic Stem Cell Transplantation
What is being tested?
IL2 and Zoledronic Acid
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteFrance
Study dates
7 May 2019to 29 Aug 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 17Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • Nantes Uh

    Nantes

Other trials in France

About this study

Official title: Phase 1 Dose Escalation of Early Infusion of Zoledronic Acid in Combination With Increasing Low-dose of Interleukin-2 in Order to Expand Vγ9Vδ2 T Cells After T-replete Haplo-identical Allogeneic Stem Cell Transplantation (SCT)

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.

Read the 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.

Being tested
IL2, Zoledronic Acid
Keywords
Haplo-SCT, Phase 1, Zoledronic acid, IL-2, g/d T cells

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IL2Drug

    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 AcidDrug

    4 mg at day +15 post graft

Study groups in NCT03862833
Study groupRoleWhat they receive
experimental groupExperimentalZoledronic 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
Receives: Drug: IL2; Drug: Zoledronic Acid
control groupNo interventionno experimental treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. determine the maximum tolerated dose (MTD) of early administration of increasing doses of low-dose IL-2 in combination with a fixed dose of Zoledronic acid after haplo-SCT

    A dose-limiting toxicity (DLT) will be defined as:

    • non-hematological toxicity of grade 4, including grade 4 acute GVHD 4.
    • non-hematological toxicity of grade 3 non-reversible for > 7 days or reappearance of the same grade 3 after reintroduction of IL2 in case of return to at least one grade 1.
    • an acute GVHD grade 2-3 for > 7 days or reappearance of GVHD grade 2-3 acute GVHD after reintroduction of IL2 if at least grade 1 acute GVHD is restored.
    • a reappearance of a grade 3/4 IL2 allergic reaction after reintroduction of IL2 in the event of a return to at least grade 1 after the occurrence of an allergic reaction of grade 3/4 IL2 when of the administration.
    • grade 4 pancytopenia with hypocellular bone marrow (no disease detection) for > 4 weeks after the last administration of IL2.

    Measured: 28 days after the last injection of IL2

Secondary outcomes (13)

  1. Engraftment

    Concentration of sustained neutrophil recovery (>500 Giga/L) with full or mixed donor chimerism documentation

    Measured: day 30, 60,90/100, 6 months and 1 year post-transplant

  2. Chimerism (mixed, full or uncompleted)

    Evaluation of CD3+ T-cell chimerism

    Measured: day 30, 60,90/100, 6 months and 1 year post-transplant

  3. overall survival

    the time from day 0 of allo-SCT to death or last follow-up for surviving patients

    Measured: last patient follow up : 36 months

  4. disease-free survival

    time from day 0 of allo-SCT to time without evidence of relapse or disease progression censored at the date of death or last follow-up.

    Measured: last patient follow up : 36 months

  5. relapse rate

    any event related to re-occurrence of the disease.

    Measured: last patient follow up : 36 months

  6. Non relapse mortality

    death from any cause without previous relapse or progression

    Measured: day 100 post transplant and one year post-transplant

  7. Incidence of acute GVHD

    Acute GVHD: Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, Bunworasate U, et al. International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016 Jan;22(1):4-10.

    Measured: day 100 post transplant one year post-transplant

  8. Hematologic and immune reconstitutions post-transplant

    median time for neutrophils recovery (first day with >0.5 Giga/L for three consecutive days) and platelets recovery >20, 50 and 100 Giga/L; T CD3, CD4, CD8, NK, B, Tregs, g/d T cells

    Measured: before the graft and at days 15, 22, 29, 36, 45, 70

  9. Complete remission (CR) rate for lymphoma patients

    Cheson criteria

    Measured: day 100 post transplant

  10. g/d T cells detection after haplo-SCT

    Evaluation of T CD3, CD4, CD8, NK, B, Tregs, g/d T cells

    Measured: before the graft and at days 15, 22, 29, 36, 45, 70

  11. Perturbation of ionic metabolism

    Evaluation of Vitamin D, Ca, Ph, Na, K, serum creatinine, bilirubin (direct and total), alkaline phosphatase, gammaGT, ALAT, ASAT

    Measured: before the graft and at days 15, 22, 29, 36, 45, 70

  12. Detection of dysthyroid disease

    Dosage of T3 T4 TSH

    Measured: before the graft and at day 70

  13. Incidence of acute and chronic GVHD

    Chronic GVHD: Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56.

    Measured: one year post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Mar 2019
  2. Study start7 May 2019
  3. Primary completion29 Aug 2023
  4. Study completion29 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
a group of patient will received IL2+ zoledronic acid a group of patient will not received IL2+ zoledronic acid
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03862833
Sponsor's protocol ID
RC18_0419
Acronym
HILDEGAZ
Status last verified
Oct 2023
First submitted
27 Feb 2019
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38165016

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing IL2 and Zoledronic Acid in people with Hematopoietic Stem Cell Transplantation, run by Nantes University Hospital at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

determine the maximum tolerated dose (MTD) of early administration of increasing doses of low-dose IL-2 in combination with a fixed dose of Zoledronic acid after haplo-SCT (time frame: 28 days after the last injection of IL2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03862833, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.

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