CARPALL: Immunotherapy with CD19+CD22 CAR T-cells for CD19+ and CD22+ Acute Lymphoblastic Leukaemia
NCT ID: NCT02443831
Last Updated: 2025-04-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
50 participants
INTERVENTIONAL
2016-04-30
2041-12-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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CD19+CD22 CAR T-cells
Patients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19+CD22CAR T-cells. Patients will receive lymphodepletion with low dose total body irradiation, fludarabine and cyclophosphamide prior to infusion of the CD19+CD22CAR T-cells.
Leukapheresis
Patients will undergo an unstimulated leukapheresis to isolate the required immune cells to produce the CD19+CD22 CAR T-cells
Total Body Irradiation (TBI)
Participants will receive total body irradiation delivered as a single fraction (2Gy) on day -7 prior to CD19+CD22CAR T-cell infusion.
Lymphodepletion with Fludarabine
Patients will receive lymphodepleting chemotherapy with iv fludarabine 30 mg/m2 on days -6 to -3 prior to CD19+CD22CAR T-cell infusion.
Lymphodepletion with Cyclophosphamide
Patients will receive lymphodepleting chemotherapy with iv cyclophosphamide 0.5 g/m2 on days -6 to -5 prior to CD19+CD22CAR T-cell infusion.
CD19+CD22 CAR T-cells
Dose level 1: 2 doses of 4 x 10\^5 CD19+CD22 CAR T-cells/kg Dose level 2: 2 doses of 1 x 10\^6 CD19+CD22 CAR T-cells/kg given as a split dose as an intravenous injection through a Hickman line or PICC line (peripherally inserted central catheter) on day 0 and day 14.
Interventions
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Leukapheresis
Patients will undergo an unstimulated leukapheresis to isolate the required immune cells to produce the CD19+CD22 CAR T-cells
Total Body Irradiation (TBI)
Participants will receive total body irradiation delivered as a single fraction (2Gy) on day -7 prior to CD19+CD22CAR T-cell infusion.
Lymphodepletion with Fludarabine
Patients will receive lymphodepleting chemotherapy with iv fludarabine 30 mg/m2 on days -6 to -3 prior to CD19+CD22CAR T-cell infusion.
Lymphodepletion with Cyclophosphamide
Patients will receive lymphodepleting chemotherapy with iv cyclophosphamide 0.5 g/m2 on days -6 to -5 prior to CD19+CD22CAR T-cell infusion.
CD19+CD22 CAR T-cells
Dose level 1: 2 doses of 4 x 10\^5 CD19+CD22 CAR T-cells/kg Dose level 2: 2 doses of 1 x 10\^6 CD19+CD22 CAR T-cells/kg given as a split dose as an intravenous injection through a Hickman line or PICC line (peripherally inserted central catheter) on day 0 and day 14.
Eligibility Criteria
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Inclusion Criteria
1. Resistant disease (\>5% blasts) at end of ALLTogether-1 protocol or equivalent induction
2. ALL with persisting high level MRD at 2nd time point of frontline national protocol (currently MRD \>10-4 at week 9 ALLTogether-1 Protocol or equivalent).
3. High risk infant ALL (age \< 6 months at diagnosis with MLL gene rearrangement and either presenting white cell count \> 300 x 10\^9/L or poor steroid early response (i.e. circulating blast count \>1x10\^9/L following 7 day steroid pre-phase of induction as per national guidelines or equivalent)
4. Any patient with t(17,19) TCF3-HLF rearrangement
5. High risk 1st relapse (defined as very early (relapse within 18 months of diagnosis) and early relapses (any patient relapsing on therapy or within 6 months of completing treatment) and any relapse with high risk genetics, namely (KMT2A (MLL) rearrangements, low hypodiploidy/near haploidy, t(17;19)(q22;p13)/TCF3-HLF, iAMP21 and t(1;19)(q21;p13)/TCF3- PBX1, t(9;22)(34.1 q11.2)/BCR-ABL1
6. Any on therapy relapse in patients age 16-24
7. Any relapse of infant ALL
8. ALL post ≥ 2nd relapse
9. Any refractory relapse of ALL (defined as \> 1% blasts by flow cytometry after a at least 1 cycle of standard chemotherapy)
10. ALL with MRD \>10-4 prior to planned stem cell transplant
11. Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant
12. Any relapse of ALL after stem cell transplant as long as planned time of CD19+CD22CAR T cell infusion is \> 4 months post-transplant
13. Early (defined as \< 6 months post-infusion) loss of B cell aplasia or any CD19+CD22+ relapse following CD19CAR T cell therapy with Tisagenlecleucel
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
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)
10. CD19 negative or CD22 negative disease
1. Severe intercurrent infection at the time of scheduled CD19+CD22 CAR T-cell infusion
2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19+CD22 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+CD22 CAR T-cell infusion. Note: Such patients will be excluded until the patient is GVHD free and off steroids
In addition, for CAR T infusion on D14: absence of CRS\>Gr2 or ICANS\>Gr2 after D0 CAR T infusion.
24 Years
ALL
No
Sponsors
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University College, London
OTHER
Responsible Party
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Principal Investigators
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Persis Amrolia
Role: STUDY_CHAIR
UCL Institute of Child Health
Locations
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Great Ormond Street Hospital
London, , United Kingdom
University College Hospital
London, , United Kingdom
Manchester Royal Children's Hospital
Manchester, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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Prof. Persis Amrolia
Role: primary
Dr Rachael Hough
Role: primary
Dr Rob Wynn
Role: primary
References
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Ghorashian S, Lucchini G, Richardson R, Nguyen K, Terris C, Guvenel A, Oporto-Espuelas M, Yeung J, Pinner D, Chu J, Williams L, Ko KY, Walding C, Watts K, Inglott S, Thomas R, Connor C, Adams S, Gravett E, Gilmour K, Lal A, Kunaseelan S, Popova B, Lopes A, Ngai Y, Hackshaw A, Kokalaki E, Carulla MB, Mullanfiroze K, Lazareva A, Pavasovic V, Rao A, Bartram J, Vora A, Chiesa R, Silva J, Rao K, Bonney D, Wynn R, Pule M, Hough R, Amrolia PJ. CD19/CD22 targeting with cotransduced CAR T cells to prevent antigen-negative relapse after CAR T-cell therapy for B-cell ALL. Blood. 2024 Jan 11;143(2):118-123. doi: 10.1182/blood.2023020621.
Kokalaki E, Ma B, Ferrari M, Grothier T, Hazelton W, Manzoor S, Costu E, Taylor J, Bulek A, Srivastava S, Gannon I, Jha R, Gealy R, Stanczuk L, Rizou T, Robson M, El-Kholy M, Baldan V, Righi M, Sillibourne J, Thomas S, Onuoha S, Cordoba S, Pule M. Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR. Mol Ther. 2023 Jul 5;31(7):2089-2104. doi: 10.1016/j.ymthe.2023.03.020. Epub 2023 Mar 21.
Ghorashian S, Kramer AM, Onuoha S, Wright G, Bartram J, Richardson R, Albon SJ, Casanovas-Company J, Castro F, Popova B, Villanueva K, Yeung J, Vetharoy W, Guvenel A, Wawrzyniecka PA, Mekkaoui L, Cheung GW, Pinner D, Chu J, Lucchini G, Silva J, Ciocarlie O, Lazareva A, Inglott S, Gilmour KC, Ahsan G, Ferrari M, Manzoor S, Champion K, Brooks T, Lopes A, Hackshaw A, Farzaneh F, Chiesa R, Rao K, Bonney D, Samarasinghe S, Goulden N, Vora A, Veys P, Hough R, Wynn R, Pule MA, Amrolia PJ. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med. 2019 Sep;25(9):1408-1414. doi: 10.1038/s41591-019-0549-5. Epub 2019 Sep 2.
Other Identifiers
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UCL 14/0529
Identifier Type: -
Identifier Source: org_study_id
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