Tisagenlecleucel vs Blinatumomab or Inotuzumab for Patients With Relapsed/Refractory B-cell Precursor Acute Lymphoblastic Leukemia (OBERON)

Tisagenlecleucel Versus Blinatumomab or Inotuzumab for Adult Patients With Relapsed/Refractory B-cell Precursor Acute Lymphoblastic Leukemia: A Randomized Open Label, Multicenter, Phase III Trial

This trial aims to compare the benefits and risks of tisagenlecleucel to blinatumomab or inotuzumab in adult patients with relapsed or refractory ALL. This trial investigates tisagenlecleucel as an additional treatment option for this patient population with high unmet medical need.

Study Overview

• Status: Withdrawn
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Biological: Tisagenlecleucel; Drug: Blinatumomab; Drug: Inotuzumab

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent.
2. Age ≥ 18 years.
3. Subject with CD19-expressing B-ALL.
4. Adequate organ function.

5. Patients considered in any of the following settings are eligible:

   1. Untreated first or second relapse
   2. Refractory to primary induction therapy
   3. Refractory to first salvage therapy or
   4. Relapse after allogenic stem cell transplant.

Exclusion Criteria:

1. Patients presenting with untreated first relapse of ALL more than 24 months after initial diagnosis
2. Presence of extra-medullary disease.
3. History or presence of clinically relevant CNS pathology, or uncontrolled CNS leukemia.
4. History of Veno-occlusive Disease (VOD).
5. Active neurological autoimmune or inflammatory disorders.
6. Active acute Graft-versus-Host Disease (GvHD), grade 2-4.

Other protocol-defined Inclusion/Exclusion may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tisagenlecleucel arm; Patient to receive tisagenlecleucel after optional bridging therapy and lymphodepleting chemotherapy.	Biological: Tisagenlecleucel; autologous cellular immunotherapy product; Other Names: KYMRIAH; CTL019
Active Comparator: Control arm; blinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy	Drug: Blinatumomab; bispecific CD19-directed CD3 T-cell engager; Other Names: BLINCYTO; Drug: Inotuzumab; CD22-directed antibody-drug conjugate; Other Names: BESPONSA; Inotuzumab ozogamicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from randomization to death for any reason	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival (EFS)	EFS, assessed up to 48 months, is defined as the date from randomization to the earliest of (a) date of death due to any cause, (b) relapse after CR/CRi, or (c) treatment failure, which is defined as failure to achieve remission within 12 weeks of randomization.	4 years
Percentage of patients who achieved MRD negative CR/CRi	Percentage of patients who achieved MRD negative CR/CRi at month 3 post randomization	4 years
Overall response rate	ORR is defined as the proportion of subjects with best overall response (BOR) of CR or CRi, where the BOR is defined as the best response recorded from randomization until the start of new anticancer therapy or the data cut-off date, whichever is earlier	4 years
Duration of response (DOR)	DOR is defined as the duration from the date when the response criteria of CR/CRi is first met to the date of relapse or death due to underlying cancer.	4 years
Probability of patients who achieved CR/CRi at month 12	Probability of achieving CR/CRi based on all response assessments between randomization and month 12. This outcome measure will be based on all randomized patients and the assessment will be up to 48 months (from randomization of the first patient until 12 months after the randomization of the last patient).	4 years
Prevalence of immunogenecity	Percentage of patients who have anti-tisagenlecleucel antibodies in the serum before randomization	4 years
Incidence of immunogenecity	Percentage of patients who develop anti-tisagenlecleucel antibodies in the serum after infusion of tisagenlecleucel	4 years
Impact of immunogenicity on clinical response	difference in response between patients with immunogenicity and patients without immunogenicity	4 years
Cellular kinetic profile by qPCR	Summary of qPCR detected tisagenlecleucel transgene concentrations	4 years
Cellular kinetics profile by flow cytometry	Summary of flow cytometry-detected tisagenlecleucel transgene concentrations	4 years
Relationship between dose and response	Relationship between the administered dose of tisagenlecleucel and response to treatment (complete response with or without hematological recovery). This assessment will be done for all patients for up to 48 months.	4 years
Relationship between exposure and response	Describe the relationship between the cellular kinetics of tisagenlecleucel overtime and response.	4 years
Relationship between dose and cellular kinetic	Describe the relationship between the dose of tisagenlecleucel actually administered and cellular kinetics	4 years
EQ-5D-3L	Patient reported outcome measure	4 years
EORTC QLQ-30	Patient reported outcome measure	4 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Anticipated): June 5, 2020
• Primary Completion (Anticipated): October 8, 2025
• Study Completion (Anticipated): January 7, 2026

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): July 9, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: CAR-T; CTL019; blinatumomab; Acute lymphoblastic leukemia; tisagenlecleucel; intouzumab
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Blinatumomab; Inotuzumab Ozogamicin
• Other Study ID Numbers: CCTL019I2301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No