Clinical trial NCT03628053: Tisagenlecleucel vs Blinatumomab or Inotuzumab for Patients With Relapsed/Refractory B-cell Precursor Acute Lymphoblastic Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Acute Lymphoblastic Leukemia
Keywords: Acute lymphoblastic leukemia
tisagenlecleucel
intouzumab
blinatumomab
CAR-T
CTL019
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-08-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 4 years
Secondary outcomes:
measure: Event Free Survival (EFS)
timeFrame: 4 years
measure: Percentage of patients who achieved MRD negative CR/CRi
timeFrame: 4 years
measure: Overall response rate
timeFrame: 4 years
measure: Duration of response (DOR)
timeFrame: 4 years
measure: Probability of patients who achieved CR/CRi at month 12
timeFrame: 4 years
measure: Prevalence of immunogenecity
timeFrame: 4 years
measure: Incidence of immunogenecity
timeFrame: 4 years
measure: Impact of immunogenicity on clinical response
timeFrame: 4 years
measure: Cellular kinetic profile by qPCR
timeFrame: 4 years
measure: Cellular kinetics profile by flow cytometry
timeFrame: 4 years
measure: Relationship between dose and response
timeFrame: 4 years
measure: Relationship between exposure and response
timeFrame: 4 years
measure: Relationship between dose and cellular kinetic
timeFrame: 4 years
measure: EQ-5D-3L
timeFrame: 4 years
measure: EORTC QLQ-30
timeFrame: 4 years
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: