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Co-infusion of Treg-enriched Donor Lymphocytes With CD3-depleted Hematopoietic Stem Cell Graft to Prevent Graft-versus Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation Among Children With Hematologic Malignancies

ConditionsAcute Myeloid Leukemia, RelapsedAcute Lymphoblastic Leukemia, High RiskAcute Myeloid Leukemia, High RiskAcute Lymphoblastic Leukemia, Relapse
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age1-25
SponsorFederal Research Institute of Pediatric Hematology, Oncology and Immunology

About this trial

Two key methods of GVHD prevention in allogeneic HSCT have a number of limitations: ex vivo T depletion is associated with an excess of infectious complications, and pharmacological immunosuppression with insufficient efficacy of GVHD prevention. Modern graft engineering technologies make it possible to create a graft with a balanced cell composition, reducing the risk of adverse events, in particular, severe forms of acute and chronic GVHD, while preserving the immunological function of the graft. In the proposed concept, enrichment of the T graft with regulatory cells will reduce the risk of GVHD and preserve a sufficient number of T lymphocytes in the graft for the formation of protective anti-infective immunity in the early stages after HSCT. The combination of partial T depletion and pharmacological immunosuppression minimized in volume and duration will combine the advantages of T depletion (early engraftment, low risk of GVHD, low risk of organ complications) and pharmacological prophylaxis (restoration of anti-infective immunity).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Informed consent signed by the patient (age 14 to 25 years) and/or his/her legal representative (age 0 to 18 years).

The patient has an indication for allogeneic hematopoietic stem cell transplantation (HSCT) established in accordance with the current regulatory framework

Planned HSCT from a haploidentical donor

The Karnofsky or Lansky score is more than 70%

Disqualifiers

Acute viral hepatitis or acute HIV infection

Hypoxemia with SaO2 <90%

Bilirubin >3 normal

Creatinine >3 norms

Trial design

Design model

Sequential

Treatments tested in this trial

  • Cyclosporine A (CsA)

    Drug

    The combination of partial T depletion and pharmacological immunosuppression minimized in volume and duration will combine the advantages of T depletion (early engraftment, low risk of GVHD, low risk of organ complications) and pharmacological prophylaxis (restoration of anti-infective immunity).

  • Sirolimus

    Drug

    Pharmacological prophylaxis of GVHD is one of the key subjects of evaluation in the current study. Since the optimal pharmacological approach is not known, the allocation of the patients to study groups will be by randomization procedure, although not for the purpose of direct comparison, but for unbiased descriptive analysis. There will be four main groups and an additional group to be open for allocation based on the main group closing for fitting the stopping rules. The details of pharmacological GVHD prevention are Sirolimus 1 mg -3 till +30 4-8 ng/ml

  • Ruxolitinib (JAKAVI®)

    Drug

    Pharmacological prophylaxis of GVHD is one of the key subjects of evaluation in the current study. Since the optimal pharmacological approach is not known, the allocation of the patients to study groups will be by randomization procedure, although not for the purpose of direct comparison, but for unbiased descriptive analysis. There will be four main groups and an additional group to be open for allocation based on the main group closing for fitting the stopping rules. The details of pharmacological GVHD prevention regimens are Ruxolitinib 5 mg -2 till +30

  • Abatacept

    Drug

    Pharmacological prophylaxis of GVHD is one of the key subjects of evaluation in the current study. Since the optimal pharmacological approach is not known, the allocation of the patients to study groups will be by randomization procedure, although not for the purpose of direct comparison, but for unbiased descriptive analysis. There will be four main groups and an additional group to be open for allocation based on the main group closing for fitting the stopping rules. Abatacept 10 mg/kg -1, +7, +14, +28

Treatment groups

64 Participants
are divided into 4 treatment groups
Group A: Cyclosporine AActive comparator 1 intervention
Group B: SirolimusActive comparator 1 intervention
Group C: RuxolitinibActive comparator 1 intervention
Group D: AbataceptActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Feasibility- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

proportion of patients who received an infusion of the planned dose of regulatory T lymphocytes (at least 80%)

Time frame
day 30
2

Safety- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Cumulative risk of GVHD Grade III-IV (target \< 5%)

Time frame
120 days after HSCT

Secondary outcomes

1

Cumulative probability of engraftment

Time frame
up to 100 day
2

Time to engraftment of neutrophils and platelets

Time frame
100 day after HSCT
3

Cumulative risk of acute GVHD Grade II-IV

Time frame
up to 100 days after HSCT
4

Cumulative risk of viral

(CMV, ADV, EBV, HHV-6) DNA detection in blood, peak viral DNA load and the duration of detectable viral DNA (each virus separately)

Time frame
at 120 day after HSCT

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Lead sponsor

Source ClinicalTrials.gov
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