An Open-Label, Single-Arm, Multicenter Study, of Combination Anti-CD3/CD7 Immunotoxin (T-Guard) for Steroid-Refractory Acute Graft-versus-Host Disease)

Xenikos24 sites in 1 country3 target enrollmentNovember 21, 2019

ConditionsSteroid-Refractory Acute Graft Versus Host Disease

InterventionsT-Guard

DrugsT-Guard

Overview

Phase: Phase 3
Intervention: T-Guard
Conditions: Steroid-Refractory Acute Graft Versus Host Disease
Sponsor: Xenikos
Enrollment: 3
Locations: 24
Primary Endpoint: Complete Response (CR)
Status: Terminated
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The study is designed as an open-label, single arm Phase III, multicenter trial to evaluate the efficacy and safety of T-Guard treatment in patients with Steroid-Refractory acute Graft versus Host Disease (SR-aGVHD).

Detailed Description

Allogeneic Hematopoietic Cell Transplantation (allo-HSCT) is a potent immunotherapy with curative potential for several hematological disorders. Improvements in survival following allo-HSCT have led to its increasing use, but the leading cause of non-relapse mortality (NRM) remains graft-versus-host-disease (GVHD. Despite recent advances in the understanding of transplantation immune tolerance, aGVHD is a frequent and major complication of allo-HSCT involving activation of donor T-lymphocytes, which ultimately causes host tissue damage. T-Guard has a rapid onset, preferential killing of activated T cells, and short half-life, leading to depletion of allo-reactive T cells and quick post-treatment reconstitution of the immune system.

Registry

clinicaltrials.gov

Start Date

November 21, 2019

End Date

February 17, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Xenikos

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patient must be at least 12.0 years of age at the time of consent.
•Patient has undergone first allo-HSCT from any donor source using bone marrow, peripheral blood stem cells, or cord blood. Recipients of nonmyeloablative, reduced intensity, and myeloablative conditioning regimens are eligible.
•Patients diagnosed with SR-aGVHD after allo-HSCT. SR is defined as aGVHD that:
•Progressed after 3 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day
•No improvement after 7 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day.
•Patients with visceral (GI and/or liver) plus skin aGVHD at prednisone (or equivalent) initiation with improvement in skin GVHD without any improvement in visceral GVHD after 7 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day
•Previously was treated with prednisone (or equivalent) of greater than or equal to 1mg/kg/day and aGVHD has developed in a previously uninvolved organ system
•Progression and no improvement are defined in the protocol. Improvement or progression in organs is determined by comparing current organ staging to staging at initiation of prednisone (or equivalent) treatment. Staging is performed per MAGIC criteria.
•Evidence of myeloid engraftment (e.g., absolute neutrophil count greater than or equal to 0.5 × 10\^9/L for 3 consecutive days if ablative therapy was previously used). Use of growth factor supplementation is allowed.
•Patients or an impartial witness (in case the patient is capable of providing verbal consent but not capable of signing the informed consent form (ICF)) should have given written informed consent. For patients less than 18 years of age, a written informed consent of the parents or guardian and written assent of the patient will be obtained, per the local requirements.

Exclusion Criteria

•Patients who have been diagnosed with overlap syndrome, that is, with any concurrent features of cGVHD.
•Patients requiring any of the following: mechanical ventilation, vasopressor support, or hemodialysis.
•Patients who have received any systemic treatment, besides steroids, as upfront treatment of aGVHD OR as treatment for SR-aGVHD.
•Patients who have severe hypoalbuminemia, with an albumin of less than or equal to 1 g/dl.
•Patients who have a CK level of greater than 5 times the upper limit of normal.
•Patients with uncontrolled infections. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
•Patients with evidence of relapsed, progressing or persistent malignancy.
•Patients with evidence of minimal residual disease requiring withdrawal of systemic immune suppression
•Patients with known hypersensitivity to any of the components murine monoclonal antibodies (mAb) or Recombinant Ricin Toxin A-chain (RTA).
•Patients who have received more than one allo-HSCT.

Arms & Interventions

T-Guard Treatment

Patients will receive T-Guard for treatment of steroid-refractory acute GVHD.

Intervention: T-Guard

Outcomes

Primary Outcomes

Complete Response (CR)

Time Frame: Day 28

Complete Response at Day 28 is defined as a score of 0 for the GVHD staging in all evaluable organs at the Day 28 visit along with freedom from additional systemic therapy for treatment of acute GVHD.

Secondary Outcomes

Relapse-free Survival(Days 180)
Overall Survival (OS)(Day 30)
Overall Response Rate (CR or Partial Response (PR))(Days 14, 28, and 56)
Proportions of CR, PR, Mixed Response (MR), no Response (NR) and Progression(Days 7, 14, 28, and 56)
Pharmacokinetics of T-Guard - CL(Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14))
Pharmacokinetics of T-Guard - t1/2(Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14))
Duration of Complete Response (DoCR)(Through Day 180)
Incidence of Toxicities(initiation of T-Guard to 28 days post-last dose)
Pharmacokinetics of T-Guard - Cinf(Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14))
Pharmacokinetics of T-Guard - AUC(Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14))
Non-Relapse Mortality (NRM)(Days 100 and 180)
GVHD-free Survival(Days 90 and 180)
Cumulative Incidence of Chronic GVHD(Day 180)
Pharmacokinetics of T-Guard - Vc(Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14))
Immunogenicity(Baseline, Days 7, 14, 28, 90, and 180)
Cumulative Incidence of Disease Relapse/Progression(Day 180)
Incidence of Systemic Infections(initiation of T-Guard to 28 days post-last dose)