A Study of CD19 Targeted CAR T Cell Therapy in Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL)
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| ClinicalTrials.gov Identifier: NCT04404660 |
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Recruitment Status :
Active, not recruiting
First Posted : May 27, 2020
Last Update Posted : August 28, 2023
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Sponsor:
Autolus Limited
Information provided by (Responsible Party):
Autolus Limited
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Brief Summary:
This is a Phase Ib/II study to evaluate the safety and efficacy of autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19 in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia (ALL).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia | Biological: AUTO1 | Phase 1 Phase 2 |
This Phase Ib/II, open-label, multi-center, single arm study is designed to evaluate the safety and efficacy of AUTO1 in adult patients with B-cell ALL by determining the overall response rate (ORR).
Adult patients with relapsed or refractory ALL will be enrolled in both phases of the study. Consented patients will go through the following five sequential stages: screening, leukapheresis, pre-conditioning, treatment, and follow-up. All patients will receive a total target dose of 410E+6 of CAR T cells as a split dose on Day 1 and on Day 10 (±2 days).
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 153 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-Label, Multi-Centre, Phase Ib/II Study Evaluating the Safety and Efficacy of AUTO1, a CAR T Cell Treatment Targeting CD19, in Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia |
| Actual Study Start Date : | March 4, 2020 |
| Estimated Primary Completion Date : | May 2025 |
| Estimated Study Completion Date : | May 2025 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
| Experimental: AUTO1 |
Biological: AUTO1
Following pre-conditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with a total target dose of 410E+6 of CD19-positive CAR T cells as a split dose on Day 1 and on Day 10 (±2 days).
Other Name: Obecabtagene autoleucel (obe-cel) |
Primary Outcome Measures :
- Phase Ib - Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after AUTO1 infusion [ Time Frame: Up to 24 months ]
- Phase II - Cohort IIA: ORR defined as proportion of patients achieving CR or CRi as assessed by an IRRC. Cohort IIB: Proportion of patients achieving MRD-negative remission by central ClonoSEQ NGS testing (<1e-4 leukemic cells) [ Time Frame: Up to 24 months ]
Secondary Outcome Measures :
- Phase II - Proportion of patients achieving MRD-negative CR by NGS (<1e-4 leukemic cells) [ Time Frame: Up to 24 months ]
- Phase II - Complete remission rate [ Time Frame: Up to 24 months ]
- Phase II - Response to AUTO1 treatment measured as duration of remission (DOR) [ Time Frame: Up to 24 months ]
- Phase II - Response to AUTO1 measured as progression-free survival (PFS). [ Time Frame: Up to 24 months ]
- Phase II -Response to AUTO1 treatment measured as overall survival (OS) [ Time Frame: Up to 24 months ]
- Phase II - Frequency and severity of AEs and SAEs [ Time Frame: Up to 24 months ]
- Phase II - Incidence of severe hypogammaglobulinaemia [ Time Frame: Up to 24 months ]
- Phase II - Duration of severe hypogammaglobulinaemia [ Time Frame: Up to 24 months ]
- Phase II - Detection of CAR T cells measured by PCR following AUTO1 infusion [ Time Frame: Up to 24 months ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age 18 years or older Age 18 years or older
- ECOG performance status of 0 or 1
- Relapsed or refractory B cell ALL
- Patients with Ph+ ALL are eligible if intolerant to TKI, failed two lines of any TKI, or failed one line of second-generation TKI, or if TKI is contraindicated
- Documented CD19 positivity within 1 month of screening
- Phase Ib: Primary Cohort IA: Presence of ≥5% blasts in BM at screening
- Phase Ib: Exploratory Cohort IB: MRD-positive defined as ≥ 1e-4 and <5% blasts in the BM at screening
- Phase II: Primary Cohort IIA: Presence of ≥5% blasts in BM at screening
- Phase II: Cohort IIB: ≥2nd CR or CRi with MRD-positive defined as ≥1e-3 by central ClonoSEQ® NGS testing and <5% blasts in the BM at screening
- Adequate renal, hepatic, pulmonary, and cardiac function
Exclusion Criteria:
- Phase Ib (Cohort IA and Cohort IB) and Phase II (Cohort IIA and Cohort IIB) B-ALL with isolated EM disease
- Diagnosis of Burkitt's leukaemia/lymphoma or CML lymphoid in blast crisis
- History or presence of clinically relevant CNS pathology
- Presence of CNS-3 disease or CNS-2 disease with neurological changes
- Presence of active or uncontrolled fungal, bacterial, viral, or other infection requiring systemic antimicrobials for management
- Active or latent Hepatitis B virus or active Hepatitis C virus
- Human Immunodeficiency Virus (HIV), HTLV-1, HTLV-2, syphilis positive test
- Prior CD19 targeted therapy other than blinatumomab. Patients who have experienced Grade 3 or higher neurotoxicity following blinatumomab.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04404660
Locations
Show 34 study locations
Sponsors and Collaborators
Autolus Limited
| Responsible Party: | Autolus Limited |
| ClinicalTrials.gov Identifier: | NCT04404660 |
| Other Study ID Numbers: |
FELIX (AUTO1-AL1) 2019-001937-16 ( EudraCT Number ) |
| First Posted: | May 27, 2020 Key Record Dates |
| Last Update Posted: | August 28, 2023 |
| Last Verified: | August 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Autolus Limited:
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B cell acute lymphoblastic leukemia Relapsed B cell acute lymphoblastic leukemia Refractory B cell acute lymphoblastic leukemia |
ALL AUTO1 CD19-positive CAR T cell |
Additional relevant MeSH terms:
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Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms |
Hematologic Diseases Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |