Infection and Tumour Antigen Cellular Therapy (INTACT-WT1)

A Clinical Trial of Donor-derived WT1 Specific T Cells for Prevention of Relapse in Combination With Multiple Pathogen Specific T Cells for Prevention of Infection in Patients Undergoing Allogeneic Haemopoietic Stem Cell Transplant for AML

This study is to test a new therapy for patients with acute myeloid leukaemia who are undergoing blood stem cell transplant. In this study, the investigators will take a small number of your immune cells whose normal function is to give immunity to infections and help to fight leukaemia. These cells will be stimulated to multiply in the laboratory and will then be given to the transplant recipient after the transplant. This is a sort of "immunity transplant". The exact purpose of this study is to investigate if these cells are safe and effective in patients having a transplant for AML.

Study Overview

• Status: Unknown
• Conditions: Leukemia, Myelocytic, Acute
• Intervention / Treatment: Biological: Donor-derived WT1-CTL and P-CTL

Detailed Description

The study will analyse the safety and biological efficacy of administering the investigational products (donor-derived Wilm's Tumour Antigen-specific cytotoxic T lymphocytes and with cytotoxic T lymphocytes specific for multiple opportunistic pathogens (cytomegalovirus (CMV), Adenovirus (Adv), Epstein Barr virus (EBV), Varicella-Zoster virus (VZV), Influenza, BK virus (BKV), and fungal infections), hereafter referred to as P-CTLs) for the prophylaxis of relapse, viral and fungal reactivation and infection following allogeneic blood or marrow transplantation for acute myeloid leukaemia. P-CTL will be given prophylactically a minimum of 28 days after transplantation followed by administration of monthly infusions of WT1-CTL for up to four doses. Our aims are to study the safety of combining WT1-CTL and P-CTL infusions; their persistence, effect on relapse of disease, effect on minimal residual disease, reconstitution of WT-1 and pathogen-specific immunity, viral reactivation, infection rates after transplantation, viral load; use of antiviral and antifungal pharmacotherapy for specific infections, hospitalisations and overall survival. Safety of infusions with respect to the development of adverse events within the first 12 months post-transplant will be assessed.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, Sydney, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital
      • Contact: Gililan Huang; Phone Number: +61 2 9845 7219

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients undergoing myeloablative or non-myeloablative allogeneic transplantation from an HLA (A, B and DR) identical or 1-3 antigen mismatched family or unrelated donor
2. Transplant performed for acute myeloid leukaemia
3. Leukaemia blasts express the WT1 tumour antigen as determined by the European LeukaemiaNet standardised assay described in 16. WT1 overexpression will be defined by greater than 250 copies/104ABL copies in bone marrow samples or greater than 50 copies/104ABL copies in peripheral blood. This assay will be performed on samples collected as part of routine clinical care at diagnosis and during initial treatment prior to transplantation. Testing will be performed after consent for trial participation has been obtained and negativity for WT1 will be classified as screening failure
4. Recipients of peripheral blood HSCT
5. Adequate hepatic and renal function (< 3 x upper limit of normal for AST, ALT, < 2 x upper limit of normal for total bilirubin, serum creatinine)
6. Estimated life expectancy of at least 12 months
7. Patient (or legal representative) has given informed consent

Exclusion Criteria:

1. Use of anti-lymphocyte globulin (ALG, ATG, Campath or other broad spectrum lymphocyte antibody) given in the 4 weeks immediately prior to infusion or planned within 4 weeks after infusion
2. Grade II or greater graft versus host disease within 1 week prior to infusion
3. Prednisone or methylprednisone at a dose of > 1 mg/kg (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion
4. Prior allogeneic HSCT
5. Privately insured in or outpatients (see Indemnity Issues, Section 11.4)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Transplant Recipient; The T cell product administration is personalized cellular therapy product, individually prepared for each participant. Donor-derived WT1-CTL and P-CTL. It's exact make up and effect is dependent on both donor and recipient characteristics and as such variability is expected in the response. These variations will be adjusted for by multiple samplings over time and collation and analysis of response in both individuals an the group as a whole. One infusion of 2 x 107/m2 P-CTLs prophylactically on or after day 28 post-allogeneic peripheral blood haemopoietic stem cell transplant (HSCT), combined with up to four infusions of 2x107/m2 WT1-CTLs.

Biological: Donor-derived WT1-CTL and P-CTL; Donor-derived WT1-CTL and P-CTL. P-CTL will be given prophylactically a minimum of 28 days after transplantation followed by administration of monthly infusions of WT1-CTL for up to four doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	2 Years

Collaborators and Investigators

• Sponsor: University of Sydney

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: February 23, 2016
• First Submitted That Met QC Criteria: September 5, 2016
• First Posted (Estimate): September 9, 2016

Study Record Updates

• Last Update Posted (Estimate): September 9, 2016
• Last Update Submitted That Met QC Criteria: September 5, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: INTACT-WT1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO