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

Phase 3

Withdrawn

• Conditions: Acute Lymphoblastic Leukemia
• Interventions: Biological: Tisagenlecleucel; Drug: Blinatumomab; Drug: Inotuzumab

• Registration Number: NCT03628053
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-06-28
• Study First Submitted QC: 2018-08-08
• Study First Posted: 2018-08-14
• Study Start: 2020-06-05
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-07
• Last Update Posted: 2020-07-09
• Primary Completion: 2025-10-08
• Study Completion: 2026-01-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control arm	Inotuzumab	blinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy
Tisagenlecleucel arm	Tisagenlecleucel	Patient to receive tisagenlecleucel after optional bridging therapy and lymphodepleting chemotherapy.
Control arm	Blinatumomab	blinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	4 years	Time from randomization to death for any reason

Secondary Outcome Measures

Name	Time	Method
Event Free Survival (EFS)	4 years	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.
Percentage of patients who achieved MRD negative CR/CRi	4 years	Percentage of patients who achieved MRD negative CR/CRi at month 3 post randomization
Overall response rate	4 years	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
Duration of response (DOR)	4 years	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.
Probability of patients who achieved CR/CRi at month 12	4 years	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).
Prevalence of immunogenecity	4 years	Percentage of patients who have anti-tisagenlecleucel antibodies in the serum before randomization
Incidence of immunogenecity	4 years	Percentage of patients who develop anti-tisagenlecleucel antibodies in the serum after infusion of tisagenlecleucel
Impact of immunogenicity on clinical response	4 years	difference in response between patients with immunogenicity and patients without immunogenicity
Cellular kinetic profile by qPCR	4 years	Summary of qPCR detected tisagenlecleucel transgene concentrations
Cellular kinetics profile by flow cytometry	4 years	Summary of flow cytometry-detected tisagenlecleucel transgene concentrations
Relationship between dose and response	4 years	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.
Relationship between exposure and response	4 years	Describe the relationship between the cellular kinetics of tisagenlecleucel overtime and response.
Relationship between dose and cellular kinetic	4 years	Describe the relationship between the dose of tisagenlecleucel actually administered and cellular kinetics
EQ-5D-3L	4 years	Patient reported outcome measure
EORTC QLQ-30	4 years	Patient reported outcome measure