RecruitingPhase 1ACTRN12618001540202

Fungus-specific immune cells for bone marrow transplant patients with invasive fungal disease

A phase 1 trial of HLA-DR matched third party donor-derived fungus-specific cytotoxic T-lymphocytes in patients with invasive fungal disease post-allogeneic stem cell transplantation

Sponsor

Western Sydney Local Health District

Enrollment

20 participants

Start Date

Feb 5, 2021

Study Type

Interventional

Conditions

Invasive Fungal Disease

Summary

Fungal infections after receiving a bone marrow transplant is lethal and requires costly anti-fungal treatment . This study will give immune cells to transplant patients to fight the infection. We hope that these immune cells will shorten the amount of anti-fungal drugs required and improve patient outcomes.

Eligibility

Sex: Both males and femalesMin Age: 1 YearsMax Age: 80 Yearss

Inclusion Criteria6

Recipients of myeloablative or non-myeloablative allogeneic stem cell transplantation from HLA-matched family or unrelated donor, mismatched family or unrelated donor or cord blood donor
Proven or probable invasive fungal disease following transplant as defined by the internationally accepted criteria of the European Organisation for Research and Treatment of Cancer and the US-based Mycoses Study Group within 1 year of allogeneic stem cell transplant
Patients has received no more than 28 days of a therapeutic dose of an anti-fungal drug prior to fungus-specific T-cell infusion (prophylactic anti-fungal agents not included). The choice of anti-fungal agents will be unrestricted and at the discretion of the treating physician
Adequate hepatic and renal function (< 5 x upper limit of normal for AST (SGOT), ALT (SGPT), < 3 x upper limit of normal for total bilirubin, serum creatinine)
ECOG status 0 to 3 or Lansky score 30-100
Patient (or legal representative) has given informed consent.

Exclusion Criteria11

Use of anti-lymphocyte globulin (ALG, ATG, Campath or other broad spectrum lymphocyte antibody) in the 4 weeks immediately prior to fungus-specific T-cell infusion or planned within 4 weeks after infusion unless anti-lymphocyte globulin levels in blood shown to be below the lympholytic threshold prior to infusion.
Active grade II or greater graft versus host disease within 1 week prior to infusion.
Prednisone or methylprednisolone at a dose of > 1 mg/kg daily (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion.
Dose of prednisone or methylprednisolone (if administered) not maintained at a stable level for 72 hours prior to T cell infusion
Active and uncontrolled relapse of malignancy
Severe peripheral cytopenia (ANC <0.5 x 10^9/L, platelet count <20 x 10^9/L unsupported)
Active uncontrolled non-fungal infection including bacterial sepsis requiring commencement of systemic intravenous antibiotics in the 48 hours prior to T-cell infusion, active tissue infection with opportunistic viruses or untreated or progressing post-transplant lymphoproliferative disease
Hypotension requiring fluid or pressor support, hypoxia or neurological features such as confusion or seizures in the 48 hours prior to T-cell infusion
Patients requiring assisted respiration (eg: CPAP/intubation)
ECOG status 4 or Lansky score <30
Privately insured in or outpatients in New South Wales participating centres

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Interventions

Phase 1 trial of three dose levels of third party, donor-derived fungus-specific cytotoxic T-lymphocytes (CTL's) in patients with invasive fungal disease post-allogeneic stem cell transplantation. Pa

Phase 1 trial of three dose levels of third party, donor-derived fungus-specific cytotoxic T-lymphocytes (CTL's) in patients with invasive fungal disease post-allogeneic stem cell transplantation. Patients will initially be given a dose of 1x10^6cells/m^2 followed by 1x10^7cells/m^2 and 1x10^8cells/m^2 no less than 14 days and no more than 3 months apart. The decision to proceed with the next infusion will be in the opinion of the treating physician and the Chief Investigator if it is in the patient’s best interest to do so. Factors such as toxicity from previous infusions, response of disease to previous infusion and concomitant medications will be considered. The infusion will be given via intravenous infusion over 5 minutes. The patient may receive the infusion as an outpatient (eg: Cancer Day Suite) but it is recommended that they remain in hospital for at least 7 days after the administration of T-cells for monitoring of potential complications of therapy. Given the patient disease it is likely they will already be an inpatient.