- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05942599
Base Edited CAR T Cells Against AML: Deep Conditioning Ahead of Allogeneic Stem Cell Transplantation (CARAML)
Phase 1 Study of Base Edited CAR T Cells Against AML: Deep Conditioning Ahead of Allogeneic Stem Cell Transplantation
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Who can participate? Patients aged 6 months to 16 years with relapsed acute myeloid leukaemia ahead of a planned bone marrow transplant.
What does the study involve? Patients will undergo careful screening to confirm that this treatment is adequate for them. Chemotherapy will be given prior to BE CAR-33 infusion to improve the ability of T-cells to establish and grow. Patients will then receive a single infusion of the BE CAR-33 cells. They will be closely monitored via blood and bone marrow tests for safety and to check the levels of BE CAR-33 and leukaemia cells. The investigators expect patients to be in hospital for 5 weeks for the BE CAR-33 therapy and the transplant will be scheduled 4 weeks after the end of BE CAR33. Patients will be monitored every month for the first three months and then every 6 months.
What are the possible benefits and risks of participating? Taking part in the study of testing 'ready-made' CAR T cells could help reduce the amount of disease and get the patient into remission before a planned bone marrow transplant. Leukaemia is less likely to come back after a bone marrow transplant if levels in the bone marrow are undetectable. The ready-made CAR T cells are being used to try and improve the chances of successful transplantation. Side effects may include low blood cell counts, infections, cytokine storm (severe immune reaction), graft versus host disease (where the donated cells attack the body) and other complications.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Robert Chiesa, Dr
- Phone Number: 8434 02074059200
- Email: robert.chiesa@gosh.nhs.uk
Study Contact Backup
- Name: Avijeet Mishra, Dr
- Email: avijeet.mishra@gosh.nhs.uk
Study Locations
-
-
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London, United Kingdom, WC1N3JH
- Recruiting
- Great Ormond Street Hospital for Children
-
Contact:
- Robert Chiesa, Doctor
- Email: robert.chiesa@gosh.nhs.uk
-
Contact:
- Avijeet Mishra
- Email: avijeet.mishra@gosh.nhs.uk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or female patients
- Age ranging between 6 months and <16 years
Medical and therapeutic criteria
- Relapsed AML ahead of scheduled allogeneic haematopoietic stem cell transplantation (allo-SCT).
- Morphologically confirmed with leukemic blasts in the bone marrow (>5%) or a quantifiable MRD by multiparameter flow cytometry and/or quantitative polymerase chain reaction (>10-4)
- CD33+ leukaemia associated immunophenotype (LAIP) on >95% of blasts
- Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available
- Estimated life expectancy ≥ 12 weeks
- Lansky (age < 16 years at the time of assent/consent) or performance status ≥ 70;
- Eastern Cooperative Oncology Group ECOG performance status < 2.
Exclusion Criteria:
- Patients/parents unwilling to undergo follow-up for 15 years
- Foreseeable poor compliance to the study procedures
- Evidence of disease progression after cytoreduction
- Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per
- National Comprehensive Cancer Network guidelines)
- Absence of suitable HLA matched or mismatched donor
- Weight < 6kgs
- Presence of donor-specific anti-HLA antibodies directed against BE-CAR33
- GvHD requiring systemic therapy
- Systemic steroid therapy prednisolone >0.5mg/kg/day
- Known hypersensitivity to test materials or related compounds
- Active bacterial, fungal or viral infections not controlled by standard of care anti- microbial or anti-viral treatment. Uncontrolled bacteraemia/ fungaemia is defined as the ongoing detection of bacteria/fungus on blood cultures despite antibiotic or anti-fungal therapy. Uncontrolled viraemia is defined as rising viral loads on two consecutive occasions despite antiviral therapy.
- Risk of pregnancy or non-compliance with contraception (if applicable). Girls of childbearing potential must have been tested negative in a pregnancy test within 14 days prior to inclusion.
- Lactating female participants unwilling to stop breastfeeding
- Prior CAR T cell therapy known to be associated with ≥Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug-related CNS toxicity
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single dose intravenous infusion of a banded dose of CAR33+ T Cells/Kg BECAR33
Patients will undergo careful screening to confirm that this treatment is appropriate for them.
Patients will receive BE CAR-33 before their scheduled bone marrow transplant.
Chemotherapy will be given prior to BE CAR-33 infusion to improve the ability of CAR T-cells to establish and grow.
Patients will then receive a single infusion of the BE CAR-33 cells and will be closely monitored in hospital for the next 4 weeks.
Patient will start chemotherapy for their scheduled bone marrow transplant 28 days after BE-CAR33 infusion unless their disease is progressing.
Patients will be monitored on the study for 1 year after transplant and then long term in routine clinics.
|
Single-dose intravenous infusion (weight-based dosing) of a banded dose of CAR33+ T cells/kg.
BECAR33 Total duration of treatment: 28 days follow up: 12 months
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frequency and description of adverse events after BE-CAR33 Infusion
Time Frame: 1 Year
|
Incidence of grade 3-5 toxicities occurring from infusion up to one year follow-up.
Severe Adverse reactions of special interest will be CRS, ICANS, GvHD and VOD.
American Society of Bone Marrow transplantation grading scales for CRS/ICANS, National institute of health criteria for GvHD and EBMT criteria for VOD will be applied.
Common terminology criteria for adverse event (CTCAE) nomenclature will be used to grade other adverse events.
|
1 Year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients achieving disease remission ahead of allo-SCT
Time Frame: 28 Days
|
Remission rate will be assessed by bone marrow and CNS evaluation after 28 days.
Disease remission is defined as morphological complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) with MRD by flow and/or PCR.
|
28 Days
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Waseem Qasim, Prof, Great Ormond Street Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 18IC13
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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