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

NCT03628053 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: CCTL019I2301
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Acute lymphoblastic leukemia; tisagenlecleucel; intouzumab; blinatumomab; CAR-T; CTL019

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Time from randomization to death for any reason

  4 years

Secondary Outcomes (15)

• Event Free Survival (EFS)

  4 years

• Percentage of patients who achieved MRD negative CR/CRi

  4 years

• Overall response rate

  4 years

• Duration of response (DOR)

  4 years

• Probability of patients who achieved CR/CRi at month 12

  4 years

Study Arms (2)

Tisagenlecleucel arm

EXPERIMENTAL

Patient to receive tisagenlecleucel after optional bridging therapy and lymphodepleting chemotherapy.

Biological: Tisagenlecleucel

Control arm

ACTIVE COMPARATOR

blinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy

Drug: Blinatumomab; Drug: Inotuzumab

Interventions

Tisagenlecleucel BIOLOGICAL

autologous cellular immunotherapy product

Also known as: CTL019, KYMRIAH

Tisagenlecleucel arm

Blinatumomab DRUG

bispecific CD19-directed CD3 T-cell engager

Also known as: BLINCYTO

Control arm

Inotuzumab DRUG

CD22-directed antibody-drug conjugate

Also known as: BESPONSA, Inotuzumab ozogamicin

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Age ≥ 18 years.
• Subject with CD19-expressing B-ALL.
• Adequate organ function.
• Patients considered in any of the following settings are eligible:
• Untreated first or second relapse
• Refractory to primary induction therapy
• Refractory to first salvage therapy or
• Relapse after allogenic stem cell transplant.

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

tisagenlecleucel; blinatumomab; Inotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a phase III, open label, multinational, randomized trial. Eligible patients will be randomized 1:1 to Tisagenlecleucel treatment strategy (tisagenlecleucel after optional bridging chemotherapy and lymphodepleting chemotherapy) or control arm treatment strategy (blinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy). The randomization will be performed stratifying for the number of prior salvage therapies (0 vs. 1) and prior allogenic stem cell transplant (yes vs. no).

Study Record Dates

• First Submitted: June 28, 2018
• First Posted: August 14, 2018
• Study Start: June 5, 2020
• Primary Completion: October 8, 2025
• Study Completion: January 7, 2026
• Last Updated: July 9, 2020

Record last verified: 2020-07