T Cell Acute Lymphoblastic Leukemia, T Cell Lymphoblastic Lymphoma
Conditions
Keywords
FRACTALL, Fratricide-Resistant, CCR9, CAR T cells
Brief summary
The goal of this clinical trial is to learn if anti-CCR9 CAR T cells (which will be made using the patient's own blood cells) are safe and which dose should be used in children and adults with T cell leukaemia and lymphoma. Participants will: * have T cells collected from their blood and these T cells will be used to make the CAR-T cells in a specialized laboratory. * be admitted at the hospital a week before the CAR T cells infusion to receive a short course of chemotherapy drugs which prepare the body to receive the CAR T cells. * be given the CAR T cells into their vein. * stay in the hospital for a minimum of 2 weeks to be closely monitored * following discharge, participants will come to the clinic for check-ups (approximately 12 visits in the first two years) * during screening, treatment and follow up visits, participants will have physical examination, collection of blood samples and bone marrow biopsies and/or imaging tests (CT/PET-CT scans) depending on their type of T-cell cancer.
Interventions
BIOLOGICALCARCCR9 T cells
Anti-CCR9 CAR T cells
Sponsors
Great Ormond Street Hospital Charity
Medical Research Council
University College, London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a multi-centre, non-randomised, open-label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) for patients with high-risk, relapsed/refractory (r/r) T-ALL/T-LBL. The trial will have 2 cohorts: Adult (≥18 years old) and Paediatric (\<18 years old).
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Relapsed or refractory T-ALL/T-LBL following at least one (≥18 years old) or two (\<18 years old) standard prior lines of combination cytotoxic therapy * CCR9-positive disease as assessed by flow cytometry * T-LBL patients only: Patients must have measurable disease * Agreement to have a pregnancy test, use adequate contraception (if applicable) * Written informed consent Key
Exclusion criteria
* ECOG performance score \>2 (patients aged ≥10 years old) OR Lanksy score ≤50% (patients aged \<10 years old) * Stem Cell Transplant patients only: active significant acute GvHD or moderate/severe chronic GvHD requiring immunosuppressive therapy and/or systemic steroids * Active CNS involvement of disease * Active hepatitis B, C or HIV infection * Oxygen saturation ≤90% on air * Bilirubin \>3 x upper limit of normal * GFR \<30 ml/min * Cardiac dysfunction * Patients receiving corticosteroids at a supraphysiological dose that cannot be discontinued * Known allergy to any component of the ATIMP * Any contraindications to lymphodepletion or to the use of cyclophosphamide or fludarabine as per local SmPC * Women who are pregnant or breastfeeding * Life expectancy \<3 months * Fulminant or rapidly progressive disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of generation of CARCCR9 T cells as evaluated by the number of therapeutic products generated. | 2 years | To determine the feasibility of semi-automated autologous CARCCR9 T cells manufacture in patients with r/r T-ALL/T-LBL, in the setting of a Phase I trial. |
| Incidence of treatment-related adverse events (safety and tolerability) | From CAR T cells infusion until 28 days post infusion | Incidence of grade 3-5 toxicity causally related to the ATIMP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expansion of CARCCR9 T cells | From CAR T cells infusion until 2 years post infusion | Frequency of circulating CARCCR9 T cells in peripheral blood |
| Potential efficacy of CARCCR9 T cells | At 1 and 2 years post CAR T cells infusion | Proportion of responders |
| Overall survival | From CAR T cells infusion (Day 0) until the date of death from any cause, assessed up to 15 years post CAR T cells infusion. | Length of time from the CAR T cells infusion until death, regardless of the cause |
| Event free survival | From CAR T cells infusion (Day 0) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 15 years post CAR T cells infusion. | Length of time after a patient receives the CAR T cells and remain free from disease progression, recurrence, or death from any cause. |
| Time to disease progression | From CAR T cells infusion (Day 0) until the date of first documented progression, assessed up to 15 years post CAR T cells infusion. | Length of time from CAR T cells infusion until disease progression |
| Persistence of CARCCR9 T cells | From CAR T cells infusion until 2 years post infusion | Persistence of circulating CARCCR9 T cells in peripheral blood |
Countries
United Kingdom
Contacts
Primary ContactFRACTALL Trial Manager
Outcome results
None listed