CARPALL: Immunotherapy With CD19/22 CAR T-cells for CD19+ Haematological Malignancies

July 18, 2022 updated by: University College, London

Immunotherapy With CD19/22 CAR Redirected T-cells for High Risk, Relapsed Paediatric CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

This study aims to evaluate the safety, efficacy and duration of response of CD19/22 Chimeric Antigen Receptor (CAR) redirected autologous T-cells in children with high risk, relapsed CD19+ and/ or CD22+ haematological malignancies.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product named CD19/22 Chimeric Antigen Receptor (CAR) T-cells (CD19/22 CAR T-cells) in children and young adults (age <24 years) with high risk, relapsed CD19+ and/or CD1922+ haematological malignancies (Acute Lymphoblastic Leukemia and Burkitt's lymphoma). Following informed consent and registration to the trial, patients will undergo an unstimulated leukapheresis for the generation of the CD19/22 CAR T-cells. Patients will receive the CD19/22CAR T-cells following lymphodepleting chemotherapy. The study will evaluate the safety, efficacy and duration of response of the CD19/22 CAR T-cells in children with high risk relapsed CD19+ and or CD22+ malignancies.

Study Type

Interventional

Enrollment (Anticipated)

33

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom
        • Great Ormond Street Hospital
      • London, United Kingdom
        • University College Hospital
      • Manchester, United Kingdom
        • Manchester Royal Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 24 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Children and young adults (age 24 years or younger) with high risk/relapsed CD19+ and / or CD22+ haematological malignancy:

    A) Resistant disease (>5% blasts) at end of UKALL 2019 guidelines or equivalent induction B) ALL with persisting high level MRD at 2nd time point of frontline national protocol (currently MRD >10-4 at week 14 UKALL2019 guidelines or equivalent).

    C) High risk infant ALL (age < 6 months at diagnosis with MLL gene rearrangement and either presenting white cell count > 300 x 109/L or poor steroid early response (i.e. circulating blast count >1x109/L following 7 day steroid pre-phase of induction as per national guidelines or equivalent) D) Intermediate risk infant ALL with MRD > 10-3 at end of induction following national guidelines or equivalent) E) High risk 1st relapse (as defined by updated IntreALL 2019 classification: bone marrow or combined relapse within 30 months of diagnosis OR any relapse within 18 months of diagnosis) F) Standard risk relapse in patients with high risk cytogenetics (defined as BCR-ABL, KMT2A rearrangement, near-haploidy (<30 chromosomes) and low hypodiploidy (30-39 chromosomes), iAMP21 and TCF3-HLF translocations).

    G) Standard risk relapse with bone marrow minimal residual disease (MRD) > 10-3 at end of re-induction H) Any on therapy relapse in patients age 16-24 I) Any relapse of infant ALL J) ALL post ≥ 2nd relapse K) Any refractory relapse of ALL (defined as > 1% blasts by flow cytometry after a at least 1 cycle of standard chemotherapy) L) ALL with MRD >10-4 prior to planned stem cell transplant M) Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant N) Any relapse of ALL after stem cell transplant O) Any relapse of Burkitt's or other CD19+ and/or CD22+lymphoma Note patients with isolated CNS relapse meeting one or more of the criteria above are eligible for the study

  2. Agreement to have a pregnancy test, use adequate contraception (if applicable)
  3. Written informed consent

Exclusion Criteria:

  • Exclusion Criteria for registration:

    1. Active Hepatitis B, C or HIV infection
    2. Oxygen saturation ≤ 90% on air
    3. Bilirubin > 3 x upper limit of normal
    4. Creatinine > 3 x upper limit of normal
    5. Women who are pregnant or breastfeeding
    6. Stem Cell Transplant patients only: active significant (overall Grade ≥ II, Seattle criteria) acute GVHD or moderate/ severe chronic GVHD (NIH consensus criteria) requiring systemic steroids.
    7. Inability to tolerate leucapheresis
    8. Karnofsky (age ≥ 10 years) or Lansky (age < 10) score ≤ 50%
    9. Pre-existing significant neurological disorder (other than CNS involvement of underlying haematological malignancy)

Exclusion criteria for CD19/22CAR T-cell infusion:

  1. Severe intercurrent infection at the time of scheduled CD19/22 CAR T-cell infusion
  2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19/22 CAR T-cell infusion
  3. Allogeneic transplant recipients with active significant acute GVHD overall grade ≥II or moderate/severe chronic GVHD requiring systemic steroids at the time of scheduled CD19/22 CAR T-cell infusion. Note: Such patients will be excluded until the patient is GVHD free and off steroids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CD19/22 CAR T-cells
Patients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19/22CAR T-cells. Patients will receive lymphodepletion with fludarabine and cyclophosphamide prior to infusion of the CD19/22CAR T-cells.
Procedure: Leukapheresis
Patients will undergo an unstimulated leukapheresis to isolate the required immune cells to produce the CD19/22 CAR T-cells
Drug: Lymphodepletion with fludarabine
Patients will receive lymphodepleting chemotherapy with iv fludarabine 30 mg/m2 on days -7 to -3 prior to CD19/22CAR T-cell infusion.
Drug: Lymphodepletion with cyclophosphamide
Patients will receive lymphodepleting chemotherapy with iv cyclophosphamide 0.5 g/m2 on days -4 to -2 prior to CD19/22CAR T-cell infusion.
Biological: CD19/22 CAR T-cells
A single dose of 1 x 10^6/kg CD19/22CAR transduced T-cells will be given as an intravenous injection through a Hickman line or PICC line(peripherally inserted central catheter) on day 0.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity evaluation following CD19/22CAR T-cell infusion
Time Frame: 1 month
The incidence of grade 3-5 toxicity occurring within 60 days of CD19/22CAR T-cell infusion. In particular, the incidence of Severe Cytokine Release Syndrome and Grade 3-5 neurotoxicity occurring within 30 days of CD19/22CAR T-cell infusion.
1 month
Molecular remission
Time Frame: 1 month
Efficacy will be assessed by determining Minimal Residual Disease in the bone marrow aspirate using immunoglobulin heavy chain (IgH) quantitative polymerase chain reaction (qPCR) and/or Next Generation Sequencing in all patients. The proportion of patients achieving molecular remission at 1 month post CD19/22CAR T-cell infusion will be determined.
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Long term molecular remission
Time Frame: 2 years
Number of patients in molecular remission without further therapy at 2 years
2 years
Frequency of circulating CD19/22 CAR T-cells
Time Frame: 2 years
Persistence and frequency of circulating CD19/22CAR T-cells in the peripheral blood by flow cytometry and qPCR analyses.
2 years
Incidence of hypogammaglobulinaemia
Time Frame: 2 years
Incidence and duration of hypogammaglobulinaemia
2 years
Relapse rate
Time Frame: 10 years
Relapse rate monitored during interventional phase and long term follow up for a total of10 years post cell infusion. Number of patients who relapsed can be summarized as a percentage or rate(for all patients registered to the trial, and also only for those who received the cell infusion).
10 years
Overall Survival
Time Frame: 10 years
Overall survival is monitored during interventional phase and long term follow up for 10 years post-CD19/22 CAR T-cell infusion. Number of patients alive can be summarized as a percentage (for all patients registered to the trial, and also only for those who received the cell infusion).
10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Investigators

  • Study Chair: Persis Amrolia, UCL Institute of Child Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2016

Primary Completion (Anticipated)

January 2, 2024

Study Completion (Anticipated)

January 1, 2032

Study Registration Dates

First Submitted

April 29, 2015

First Submitted That Met QC Criteria

May 13, 2015

First Posted (Estimate)

May 14, 2015

Study Record Updates

Last Update Posted (Actual)

July 21, 2022

Last Update Submitted That Met QC Criteria

July 18, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCL 14/0529

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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