Back to resultsAPRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma (APRIL)
Primary Purpose
Multiple Myeloma
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AUTO2
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma, AUTO2
Eligibility Criteria
Key Inclusion Criteria:
- Male or female patients, aged ≥ 18.
- Willing and able to give written, informed consent.
- Confirmed diagnosis of MM.
- Measurable disease as defined by IMWG.
- Relapse or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor, alkylator and immunomodulatory therapy (IMiD), or have "double refractory" disease to a proteasome inhibitor and IMiD.
- For females of childbearing potential, a negative serum or urine pregnancy test must be documented at screening and confirmed before receiving study treatment.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
- Peripheral blood total lymphocyte count > 0.5 x 10⁹/L.
Key Exclusion Criteria:
- Women who are pregnant or lactating.
- Prior treatment with investigational or approved gene therapy or cell therapy products.
- Patient has previously received an allogenic stem cell transplant.
- Clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event.
- Left Ventricular Ejection fraction < 50 unless the institutional lower limit of normal is lower.
- Significant liver disease: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × ULN, or total bilirubin > 2.0 mg/dL or evidence of end stage liver disease (e.g. ascites, hepatic encephalopathy).
- Chronic renal impairment requiring dialysis, or calculated creatinine clearance < 30 mL/min
- Active infectious bacterial or viral disease (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus or syphilis) requiring treatmenUse of rituximab within the last 3 months.
- Active autoimmune disease requiring immunosuppression.
- Received any anti-myeloma therapy within the last 21 days prior to preconditioning or 10 days prior to leukapheresis; steroids of up to 160 mg of dexamethasone are permitted so long as > 7 days post-dose prior to pre-conditioning or leukapheresis.
- Known allergy to albumin, dimethyl sulfoxide (DMSO), cyclophosphamide or fludarabine.
Sites / Locations
- VU University Medical Centre Amsterdam
- University College London Hospitals NHS Foundation Trust
- The Christie NHS Foundation Trust
- Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AUTO2
Arm Description
Relapsed or refractory Myeloma patients
Outcomes
Primary Outcome Measures
Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period
Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT)
Dose limiting toxicity was defined as:
Any new non-hematological AE of Grade 3 or higher toxicity using the NCI CTCAE (Version 4.03), which is probably or definitely related to AUTO2 therapy, which occurs within the DLT evaluation period, and which fails to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; A Grade 4 CRS; Any other reason for activation of the safety switch after receiving AUTO2; Any other fatal event (Grade 5) or life-threatening event (Grade 4) that cannot be managed with conventional supportive measures or which in the opinion of the SEC necessitates dose reduction or other modification to trial treatment to avoid a similar hazard in future patients. Effort should be made to perform an autopsy in case of fatal event where the aetiology is unclear; Any event that in the opinion of treating investigators and/or Medical Monitor puts the patient at undue risk may also be considered a DLT.
Number of Infused Patients With Best Overall Response
Best overall response was defined as stringent complete response + complete response + very good partial response + partial response following treatment with AUTO2. Response Criteria Per IMWG Consensus Recommendations
Secondary Outcome Measures
Proportion of Patients for Whom an AUTO2 Product Can be Generated
Feasibility of product generation was examined by assessing the number of AUTO2 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients registered).
Clinical Benefit Rate
Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2
Duration of Response
Calculated from the date of first observation of sCR, CR, VGPR or PR to the date of disease progression, relapse or death, for patients who were considered responders (achieved at least PR). Patients who had not progressed, relapsed or died will be censored at the last adequate disease assessment.
Time to Disease Progression
Calculated from the date of AUTO2 treatment to the date of progression. Patients who had not progressed, relapsed or died without progression/relapse will be censored at the last adequate disease assessment.
Progression-free Survival
Calculated from the date of AUTO2 treatment to the date of progression or death. Patients who have not progressed or relapsed was censored at the last adequate disease assessment
Overall Survival
Descriptive analysis based on number of patients alive at database lock (1-May-2020).
Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood
Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03287804
Brief Title
APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma
Acronym
APRIL
Official Title
A Single-Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Terminated
Why Stopped
Preliminary efficacy seen to date following treatment with AUTO2 has been determined not sufficient to warrant further development
Study Start Date
May 5, 2017 (Actual)
Primary Completion Date
September 5, 2019 (Actual)
Study Completion Date
September 5, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Autolus Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to test the safety and efficacy of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients with Relapsed or Refractory Multiple Myeloma.
Detailed Description
The study will consist of 2 phases, a Phase I/dose escalation phase and a Phase II/expansion phase. Patients with relapsed and relapsed or refractory multiple myeloma will be enrolled in both phases of the study. Eligible patients will undergo leukapheresis in order to harvest T cells, which is the starting material for the manufacture of the autologous CAR T product AUTO2. AUTO2 has a dual target BCMA (B cell maturation antigen) and TACI (Transmembrane activator and calcium modulator and cyclophilin ligand interactor). Following pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO2 intravenously as a single or split dose and will then enter a 12-month follow-up period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma, AUTO2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AUTO2
Arm Type
Experimental
Arm Description
Relapsed or refractory Myeloma patients
Intervention Type
Biological
Intervention Name(s)
AUTO2
Intervention Description
AUTO2 (APRIL CAR T Cells) Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with doses from 15 x 10⁶ to 350 x 10⁶ APRIL CAR T Cells.
Following Phase 2 dose determination patients will be treated with selected dose of APRIL CAR T Cells
Primary Outcome Measure Information:
Title
Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period
Time Frame
Up to 28 days post-infusion
Title
Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT)
Description
Dose limiting toxicity was defined as:
Any new non-hematological AE of Grade 3 or higher toxicity using the NCI CTCAE (Version 4.03), which is probably or definitely related to AUTO2 therapy, which occurs within the DLT evaluation period, and which fails to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; A Grade 4 CRS; Any other reason for activation of the safety switch after receiving AUTO2; Any other fatal event (Grade 5) or life-threatening event (Grade 4) that cannot be managed with conventional supportive measures or which in the opinion of the SEC necessitates dose reduction or other modification to trial treatment to avoid a similar hazard in future patients. Effort should be made to perform an autopsy in case of fatal event where the aetiology is unclear; Any event that in the opinion of treating investigators and/or Medical Monitor puts the patient at undue risk may also be considered a DLT.
Time Frame
Up to 28 days post-infusion
Title
Number of Infused Patients With Best Overall Response
Description
Best overall response was defined as stringent complete response + complete response + very good partial response + partial response following treatment with AUTO2. Response Criteria Per IMWG Consensus Recommendations
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Proportion of Patients for Whom an AUTO2 Product Can be Generated
Description
Feasibility of product generation was examined by assessing the number of AUTO2 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients registered).
Time Frame
Up to 2 years
Title
Clinical Benefit Rate
Description
Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2
Time Frame
Up to 2 years
Title
Duration of Response
Description
Calculated from the date of first observation of sCR, CR, VGPR or PR to the date of disease progression, relapse or death, for patients who were considered responders (achieved at least PR). Patients who had not progressed, relapsed or died will be censored at the last adequate disease assessment.
Time Frame
Up to 2 years
Title
Time to Disease Progression
Description
Calculated from the date of AUTO2 treatment to the date of progression. Patients who had not progressed, relapsed or died without progression/relapse will be censored at the last adequate disease assessment.
Time Frame
Up to 2 years
Title
Progression-free Survival
Description
Calculated from the date of AUTO2 treatment to the date of progression or death. Patients who have not progressed or relapsed was censored at the last adequate disease assessment
Time Frame
Up to 2 years
Title
Overall Survival
Description
Descriptive analysis based on number of patients alive at database lock (1-May-2020).
Time Frame
Up to 2 years
Title
Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood
Description
Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Male or female patients, aged ≥ 18.
Willing and able to give written, informed consent.
Confirmed diagnosis of MM.
Measurable disease as defined by IMWG.
Relapse or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor, alkylator and immunomodulatory therapy (IMiD), or have "double refractory" disease to a proteasome inhibitor and IMiD.
For females of childbearing potential, a negative serum or urine pregnancy test must be documented at screening and confirmed before receiving study treatment.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
Peripheral blood total lymphocyte count > 0.5 x 10⁹/L.
Key Exclusion Criteria:
Women who are pregnant or lactating.
Prior treatment with investigational or approved gene therapy or cell therapy products.
Patient has previously received an allogenic stem cell transplant.
Clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event.
Left Ventricular Ejection fraction < 50 unless the institutional lower limit of normal is lower.
Significant liver disease: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × ULN, or total bilirubin > 2.0 mg/dL or evidence of end stage liver disease (e.g. ascites, hepatic encephalopathy).
Chronic renal impairment requiring dialysis, or calculated creatinine clearance < 30 mL/min
Active infectious bacterial or viral disease (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus or syphilis) requiring treatmenUse of rituximab within the last 3 months.
Active autoimmune disease requiring immunosuppression.
Received any anti-myeloma therapy within the last 21 days prior to preconditioning or 10 days prior to leukapheresis; steroids of up to 160 mg of dexamethasone are permitted so long as > 7 days post-dose prior to pre-conditioning or leukapheresis.
Known allergy to albumin, dimethyl sulfoxide (DMSO), cyclophosphamide or fludarabine.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Autolus Limited
Organizational Affiliation
Sponsor GmbH
Official's Role
Study Director
Facility Information:
Facility Name
VU University Medical Centre Amsterdam
City
Amsterdam
Country
Netherlands
Facility Name
University College London Hospitals NHS Foundation Trust
City
London
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust
City
Newcastle upon Tyne
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma
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