Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

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

AUTO2

Autolus Limited

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.

APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma

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

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.

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

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).

Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2

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.

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.

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

Descriptive analysis based on number of patients alive at database lock (1-May-2020).

Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Netherlands

United Kingdom

Region of Enrollment

Early termination leading to small numbers of patients analyzed

Clinical Project Manager

Patients who received at least 1 dose (complete or partial) of AUTO2 therapy (infused set)

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)

All patients who received at least 1 dose (complete or partial) of AUTO2 therapy in Phase I of the study were included in this analysis. No patients were enrolled in Phase II as the study was early terminated in Phase I. 2 patients were retreated; their best overall response is presented for this endpoint

Number of Infused Patients With Best Overall Response

Proportion of Patients for Whom an AUTO2 Product Can be Generated

All patients who received at least 1 dose (complete or partial) of AUTO2 therapy in Phase I of the study were included in this analysis. 2 patients were retreated; their best overall response is presented for this endpoint

Clinical Benefit Rate

Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the duration of response. The study was terminated early and Phase 2 was not started.

Duration of Response

Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the time to disease progression. The study was terminated early and Phase 2 was not started.

Time to Disease Progression

Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the progression-free survival. The study was terminated early and Phase 2 was not started.

Progression-free Survival

All patients who receive at least 1 dose (complete or partial dose) of AUTO2 therapy

Spots Global Cancer Trial Database for APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma

Trial Identification

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Interventions

Study Description

Keywords

Eligibility

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