A Phase 1/2 interventional study of AUTO2 in Multiple Myeloma, sponsored by Autolus Limited. Terminated at 4 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-10-23.
Sponsored by Autolus Limited · Phase 1/2, Interventional, and Treatment
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.
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.
Key Inclusion Criteria:
Key Exclusion Criteria:
Relapsed or refractory Myeloma patients
Biological: AUTO2
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
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
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.
Time frame: Up to 28 days post-infusion
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
Time frame: Up to 2 years
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).
Time frame: Up to 2 years
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
Time frame: Up to 2 years
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 frame: Up to 2 years
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.
Time frame: Up to 2 years
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
Time frame: Up to 2 years
Overall Survival
Descriptive analysis based on number of patients alive at database lock (1-May-2020).
Time frame: Up to 2 years
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.
Time frame: Up to 2 years
Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients were treated with doses from 15 x 10⁶ to 350 x 10⁶ APRIL CAR T Cells.
| Milestone | AUTO2 |
|---|---|
| Started | 12 |
| Leukaperesed | 12 |
| Started pre-conditioning therapy | 11 |
| Received study treatment | 11 |
| Completed | 1 |
| Not completed | 11 |
| Withdrew: Death | 1 |
| Withdrew: Physician decision | 2 |
| Withdrew: Progressive disease | 8 |
| Participants | AUTO2 |
|---|---|
| Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period | 0 |
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.
| Participants | AUTO2 |
|---|---|
| Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT) | 0 |
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
| Participants | AUTO2 |
|---|---|
| Number of Infused Patients With Best Overall Response | 4 |
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).
| Participants | AUTO2 |
|---|---|
| Proportion of Patients for Whom an AUTO2 Product Can be Generated | 12 |
Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2
| Participants | AUTO2 |
|---|---|
| Clinical Benefit Rate | 4 |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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
No measurements were reported for this outcome.
Descriptive analysis based on number of patients alive at database lock (1-May-2020).
| Participants | AUTO2 |
|---|---|
| Overall Survival | 3 |
Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.
| Participants | AUTO2 |
|---|---|
| Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood | 9 |
Collected over From Day 0 until Day 60 post last AUTO2 infusion.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| AUTO2 | 8/11 (72.7%) | 6/11 (54.5%) | 11/11 (100%) |
| Event | AUTO2 |
|---|---|
| PyrexiaGeneral disorders | 2/11 |
| Neutrophil count decreasedInvestigations | 1/11 |
| Metaplastic breast carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/11 |
| Acute myocardial infarctionCardiac disorders | 1/11 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 1/11 |
| HedacheNervous system disorders | 1/11 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 1/11 |
| HypocalcaemiaMetabolism and nutrition disorders | 1/11 |
| Lung infectionInfections and infestations | 1/11 |
| Event | AUTO2 |
|---|---|
| AnaemiaBlood and lymphatic system disorders | 9/11 |
| Neutrophil count decreasedInvestigations | 7/11 |
| FatigueGeneral disorders | 6/11 |
| PyrexiaGeneral disorders | 6/11 |
| DiarrhoeaGastrointestinal disorders | 5/11 |
| ChillsGeneral disorders | 4/11 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 4/11 |
| Bone painMusculoskeletal and connective tissue disorders | 4/11 |
| Oedema peripheralGeneral disorders | 3/11 |
| NeutropeniaBlood and lymphatic system disorders | 3/11 |
| Age, Categorical(Participants) | AUTO2 |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 9 |
| >=65 years | 3 |
| Sex: Female, Male(Participants) | AUTO2 |
|---|---|
| Female | 3 |
| Male | 9 |
| Ethnicity (NIH/OMB)(Participants) | AUTO2 |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 12 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | AUTO2 |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 10 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | AUTO2 |
|---|---|
| Netherlands | 1 |
| United Kingdom | 11 |
Documents are hosted by the registry — open the source record to download them.
This study is terminated, as verified in Sep 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Autolus Limited