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Haploidentical Hematopoietic Stem Cell TransplantationPhase 2NCT04778618

Individualized Dose Study of ATG in Haploidentical Hematopoietic Stem Cell Transplantation

A Phase 2 study testing Antithymocyte Globulin in people with Haploidentical Hematopoietic Stem Cell Transplantation, run by Chinese PLA General Hospital at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study is to determine the response and toxicity rate of two different dosages (Individualized dosage VS. fixed dosage) of ATG as a prophylaxis for acute GVHD in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). Read more about this study

Who is it for?
Ages 14 to 60 years
What is being tested?
Antithymocyte Globulin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
1 siteChina
Study dates
1 Dec 2020to 14 Jan 2024
Phase
Phase 2
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 14 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Confirmed diagnosis of hematological malignancies refer to the 2016 WHO classification.
  • Aged 14 to 60 years.
  • Karnofsky or Lansky performance status [27] ≥ 70%. Please refer to Appendix A.
  • First transplantation.
  • Adequate organ function
  • Patient and/or legal guardian must sign informed consent for HSCT.

Who cannot join

  • Ex-vivo T-cell depleted grafts.
  • Pregnancy or breast-feeding or unwilling to use proper contraception.
  • Unable to assess whether the malignancy is in complete remission.
  • History of hypersensitivity to any biological product.
  • Sensibility to rabbit proteins or previous treatment with Thymoglobuline®.
  • Subjects with uncontrollable systemic infection (viral, bacterial or fungal).
  • Participation in other trial in which the dose of Thymoglobuline® is fixed other than individualized dose.
  • Unable to sign the informed consent form.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Chinese PLA General Hospital

    Beijing, Beijing Municipality, 100853

Other trials in China

About this study

Official title: Impact of Optimal Doses of Antithymocyte Globulin Conditioning on Graft-versus- Host Disease and Virus Reactivation in Haploidentical Hematopoietic Stem Cell Transplantation

The purpose of this study is to determine the response and toxicity rate of two different dosages (Individualized dosage VS. fixed dosage) of ATG as a prophylaxis for acute GVHD in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT).

Read the detailed description

Acute graft-versus-host disease (aGvHD) is an important complication of haplo-HSCT. The Seattle group initially introduced the use of ATG as a treatment for acute graft-versus-host disease (aGVHD) in allogeneic hematopoietic stem cell transplantation (haplo-PBSCT) recipients. Presently, in both myeloablative and reduced-intensity conditioning (RIC) haplo-PBSCT, ATG is part of postengraftment immunosuppressive regimens.

The regimens for prophylaxis of GVHD based on 10mg/kg rabbit anti-human thymocyte immunoglobin (ATG, Thymoglobulin®, Genzyme Polyclonals S.A.S) effectively reduced the occurrence of grade II-IV aGvHD. However, the incidence of cytomegalovirus (CMV) and EB virus (EBV) reactivation were higher due to a slower immune reconstitution. The 100-day cumulative incidence of CMV and EBV viremia were both over 70% in our unmanipulated haplo-PBSCT program. The optimal dose of ATG balancing the efficacy of GVHD prophylaxis and the risk of virus reactivation in haplo-PBSCT remains unknown.

Reports on the pharmacokinetics of Thymoglobulin in allo-HSCT revealed a high variability. Recent pharmacokinetic studies have shown that the half-life of total ATG after transplant is longer than the active ATG (which is available to bind to human lymphocytes and causes the desired immunological effects). And active ATG appears more associated with pharmacodynamics effects. The investigators found that virus reactivation and acute GVHD were highly affected by ATG exposure (area under the curve, AUC) in previous cohort study. The investigators have found an optimal range of active ATG exposure balancing the efficacy of GVHD prophylaxis and the risk of virus reactivation. The incidence of CMV reactivation and III-IV aGVHD reduced to 60%, 6% respectively.

The results suggested that Individualized dosing of ATG has a potential advantage in balancing the efficacy of GVHD prophylaxis and the risk of virus reactivation in haplo-PBSCT. This may improve the survival and quality of life of patients undergoing haplo-PBSCT. A prospective randomized trial is required to compare the efficacy of Individualized dosage of ATG as a prophylaxis for acute GVHD in haplo-PBSCT.

Being tested
Antithymocyte Globulin

What participants receive

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

  • Antithymocyte GlobulinDrug

    Individual dose of ATG was Intravenous infused every day from day -5 to day -2 (total ATG dose was calculated based on pharmacokinetic index, within a range of 6 mg/kg to 10mg/kg). Antithymocyte globulin (ATG) was added to conditioning regimens for 4 days (days -5 and -2). Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine A (CsA), mycophenolate mofetil (MMF) and short-term methotrexate

Study groups in NCT04778618
Study groupRoleWhat they receive
Individual dose of ThymoglobulinExperimentalIndividual dose of Thymoglobulin (r-ATG) : Individual dose of ATG was Intravenous infused every day from day -5 to day -2 (total ATG dose was calculated based on pharmacokinetic index, within a range of 6 mg/kg to 10mg/kg)
Receives: Drug: Antithymocyte Globulin

What is being measured

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

  1. The cumulative incidences of CMV reactivation

    The cumulative incidences of CMV reactivation in participants after transplantation, tested by realtime PCR

    Measured: 180 days after transplantation

  2. The cumulative incidences of EBV reactivation

    The cumulative incidences of EBV reactivation in participants after transplantation, tested by realtime PCR

    Measured: 180 days after transplantation

Secondary outcomes (7)

  1. Engraftment

    Neutrophil engraftment was defined as the first day with a neutrophil count > 0.5 × 10^9/L on three consecutive days postnadir; platelet engraftment was defined as the first day with a platelet count > 20 × 10^9/L without transfusion for five consecutive days postnadir.

    Measured: 28 days after transplantation

  2. The cumulative incidences of aGVHD (refer to MAGIC criteria)

    Defined as the proportion of participants who developed acute GVHD

    Measured: 100 days after transplantation

  3. The cumulative incidences of cGVHD (refer to NIH criteria)

    cGvHD was diagnosed and graded according to the 2014 National Institutes of Health (NIH) consensus criteria: mild, moderate or severe respectively.

    Measured: 2 years after transplantation

  4. Relapse

    Defined as reappearance of leukemic blasts in peripheral blood or ≥5% blasts in BM or reappearance or new appearance of extramedullary leukemia.

    Measured: 1 years after transplantation

  5. Nonrelapse mortality (NRM)

    Defined as death due to causes other than malignancy relapse

    Measured: 1 years after transplantation

  6. Disease-free survival (DFS)

    Defined as survival with no evidence of relapse or progression.

    Measured: 1 years after transplantation

  7. Overall survival (OS)

    Defined as the time from transplantation to last follow-up or death due to any cause

    Measured: 1 year after transplantation

Timeline

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

  1. First posted3 Mar 2021
  2. Study start1 Dec 2020
  3. Primary completion31 Jul 2022
  4. Study completion14 Jan 2024 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
63 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04778618
Sponsor's protocol ID
S2020-484-01
Status last verified
Apr 2023
First submitted
24 Feb 2021
Last updated
11 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Call SK, Kasow KA, Barfield R, Madden R, Leung W, Horwitz E, Woodard P, Panetta JC, Baker S, Handgretinger R, Rodman J, Hale GA. Total and active rabbit antithymocyte globulin (rATG;Thymoglobulin) pharmacokinetics in pediatric patients undergoing unrelated donor bone marrow transplantation. Biol Blood Marrow Transplant. 2009 Feb;15(2):274-8. doi: 10.1016/j.bbmt.2008.11.027.

    PubMed 19167688

  • Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, Gallagher G, Kerr H, Kuruvilla J, Lee SJ, Moore J, Nevill T, Popradi G, Roy J, Schultz KR, Szwajcer D, Toze C, Foley R; Canadian Blood and Marrow Transplant Group. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016 Feb;17(2):164-173. doi: 10.1016/S1470-2045(15)00462-3. Epub 2015 Dec 24.

    PubMed 26723083

  • Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Sacchi N, van Lint MT, Bosi A; Gruppo Italiano Trapianti Midollo Osseo (GITMO). Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant. 2006 May;12(5):560-5. doi: 10.1016/j.bbmt.2005.12.034.

    PubMed 16635791

  • Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Barbanti M, Sacchi N, Van Lint MT, Bosi A. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001 Nov 15;98(10):2942-7. doi: 10.1182/blood.v98.10.2942.

    PubMed 11698275

  • Remberger M, Svahn BM, Mattsson J, Ringden O. Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation. Transplantation. 2004 Jul 15;78(1):122-7.

    PubMed 15257050

  • Wang H, Wang N, Wang L, Du J, Li F, Shao Y, Peng B, Luan S, Wang L, Jin X, Gao C, Dou L, Liu D. Targeted dosing of anti-thymocyte globulin in adult unmanipulated haploidentical peripheral blood stem cell transplantation: A single-arm, phase 2 trial. Am J Hematol. 2023 Nov;98(11):1732-1741. doi: 10.1002/ajh.27068. Epub 2023 Sep 14.

    PubMed 37706580

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Antithymocyte Globulin in people with Haploidentical Hematopoietic Stem Cell Transplantation, run by Chinese PLA General Hospital at 1 site in China.

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 6 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 11 Apr 2023. 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 China. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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?

The cumulative incidences of CMV reactivation (time frame: 180 days after transplantation). The study lists 2 primary outcomes in all. 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 NCT04778618, which also lists 6 linked publications.

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 11 Apr 2023.

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