Clinical trial NCT04521231: A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients
Official title: A Phase 1/2 Open-label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: B Cell Precursor Acute Lymphoblastic Leukemia
Keywords: R/R B-ALL
Blincyto®
AMG 103
Blinatumomab
Acute lymphoblastic leukemia (ALL)
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2020-08-20
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The study aims to evaluate the safety, efficacy, and tolerability of subcutaneous (SC) blinatumomab for treatment of Acute Lymphoblastic Leukemia (ALL), to determine the maximum tolerated dose (MTD), and recommended phase 2 dose(s) (RP2D) of SC administered blinatumomab. It will also conduct a clinical PK evaluation of SC1 and SC2 blinatumomab formulations.


Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older (or same or greater than legal age within the country if it is older than 18 years).
* Participants with B-precursor ALL with any of the following:

  * Either refractory to primary induction therapy or refractory to at least 1 salvage therapy OR
  * In untreated first, second, third or greater relapse or refractory relapse

    * First Relapse is defined as achievement of first Complete Remission (CR) \[CR1\] during upfront therapy then relapse during or after continuation therapy
    * Primary Refractory disease is defined as the absence of CR after standard induction therapy
    * Refractory relapse is defined as lack of CR after salvage treatment
    * Second relapse or later relapse is defined as relapse after achieving a second CR (CR2) in first or later salvage
    * Refractory to salvage is defined as no attainment of CR after salvage
* Relapsed or Refractory at any time after first salvage therapy.
* Relapse at any time after allogenic hematopoietic stem cell transplant (HSCT).
* Greater than or equal to 5% blasts in the Bone Marrow (Exception: Isolated Non-central nervous system (CNS) extramedullary disease \[EMD\]).
* Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
* Participants with relapse or refractory B Cell ALL Ph+ disease and that are intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.

The above is a summary, other inclusion criteria details may apply.

Exclusion Criteria:

* Active ALL in the central nervous system (CNS). Presence of greater than 5 white blood cells per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present and/or clinical signs of CNS leukemia.
* History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis or severe (≥ grade 3) CNS events including immune effector cell-associated neurotoxicity syndrome (ICANS) from prior chimeric antigen receptor T-cell (CAR T) or other T cell engager therapies.
* Isolated Extramedullary (EM) Disease
* Symptoms and/or signs that indicate an acute or uncontrolled chronic infection, any other disease or condition that could be exacerbated by the treatment or would complicate protocol compliance.
* Testicular leukemia
* History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy.
* Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy.
* Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions).
* Immunotherapy within 4 weeks before start of protocol-specified therapy. Prior failed cluster of differentiation (CD19) directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed, if treatment ended more than 4 weeks prior to start of protocol therapy therapy and no prior CNS complications.
* Currently receiving treatment in or less than 30 days or 5 half lives since ending treatment on another investigational study(ies).
* Abnormal screening laboratory parameters.
* Female participant: Expected to breastfeed during treatment and for 96 hours after the last dose of investigational product (SC blinatumomab).

The above is a summary, other exclusion criteria details may apply.

Primary outcomes:
measure: Dose Escalation Phase: Number of participants who experience dose limiting toxicities (DLTs)
timeFrame: Up to 29 days
measure: Dose Escalation Phase: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)
timeFrame: Up to approximately 28 weeks
measure: Dose Escalation Phase: Number of participants who experience one or more serious TEAEs
timeFrame: Up to approximately 28 weeks
measure: Dose Escalation Phase: Number of participants who experience one or more treatment-related treatment-emergent adverse events
timeFrame: Up to approximately 28 weeks
measure: Dose Escalation Phase: Number of participants who experience one or more adverse events (AEs) of Interest (AEIs)
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase (R/R B-ALL): Number of participants who achieve complete remission (CR)
timeFrame: Up to 68 days
measure: Dose Expansion Phase (R/R B-ALL): Number of participants who achieve complete remission with partial hematological recovery (CRh)
timeFrame: Up to 68 days
measure: Phase 2 Ph-IIC: Maximum concentration (Cmax) of blinatumomab SC1 and SC2
timeFrame: Up to approximately 4 weeks
measure: Phase 2 Ph-IIC: Average concentration (Cavg) of blinatumomab SC1 and SC2
timeFrame: Up to approximately 4 weeks
measure: Phase 2 Ph-IIC: Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2
timeFrame: Up to approximately 4 weeks
measure: Phase 2 Ph-IIC: Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2
timeFrame: Up to approximately 4 weeks
Secondary outcomes:
measure: Dose Escalation Phase: Minimum concentration over the dosing interval (Cmin) of blinatumomab
timeFrame: Up to approximately 28 weeks
measure: Dose Escalation Phase: Cmax of blinatumomab
timeFrame: Up to approximately 28 weeks
measure: Dose Escalation Phase: Tmax of blinatumomab
timeFrame: Up to approximately 28 weeks
measure: Dose Escalation Phase: AUC of blinatumomab
timeFrame: Up to approximately 28 weeks
measure: Dose Escalation Phase and Phase 2 (Ph-IIC cohort): Number of participants who achieve CR/CRh
timeFrame: Up to 68 days
measure: Dose Escalation, Dose Expansion, and Ph-IIC: Number of participants with incidence of anti-blinatumomab antibody formation
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase: Cmin of blinatumomab
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase: Cmax of blinatumomab
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase: Tmax of blinatumomab
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase: AUC of blinatumomab
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Relapse-Free Survival in participants who achieve CR/CRh within the first 2 cycles(R/R B-ALL)
timeFrame: Up to 68 days
measure: Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Overall survival (OS)
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Duration of complete response
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more TEAEs
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more serious treatment-emergent adverse event
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more treatment-related treatment-emergent adverse events
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more AEIs
timeFrame: Up to approximately 28 weeks
measure: Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Summary scores of quality of life at each assessment as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30)
timeFrame: Baseline (Day 1) up to approximately 28 weeks
measure: Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Change from baseline of quality of life as assessed by the EORTC QLQ-C30
timeFrame: Baseline (Day 1) up to approximately 28 weeks
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: New York
country: United States
facility: New York University Grossman School of Medicine and New York University Langone Hospitals
state: New York
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health, Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Wien
country: Austria
facility: Universitaetsklinikum Allgemeines Krankenhaus Wien
city: Calgary
country: Canada
facility: Arthur J E Child Comprehensive Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
city: Nice cedex 3
country: France
facility: Centre Hospitalier Universitaire de Nice
city: Paris
country: France
facility: Hopital Saint Antoine
city: Toulouse cedex 9
country: France
facility: Institut Universitaire du Cancer Toulouse Oncopole
city: Augsburg
country: Germany
facility: Universitaetsklinikum Augsburg
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni xxiii
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant Orsola
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Roma
country: Italy
facility: Azienda Ospedaliera Policlinico Umberto I
city: Akita-shi
country: Japan
facility: Akita University Hospital
state: Akita
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Fukushima-shi
country: Japan
facility: Fukushima Medical University Hospital
state: Fukushima
city: Yokohama-shi
country: Japan
facility: Yokohama City University Medical Center
state: Kanagawa
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalucía
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca Hospital Universitario de Salamanca
state: Castilla León
city: Badalona
country: Spain
facility: Institut Catala d Oncologia Badalona Hospital Universitari Germans Trias i Pujol
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
state: Comunidad Valenciana
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Istanbul
country: Turkey
facility: Bagcilar Medipol Mega Universite Hastanesi
city: Izmir
country: Turkey
facility: Izmir Ekonomi Universitesi Medical Point Hastanesi
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Jabbour E, Zugmaier G, Agrawal V, Martinez-Sanchez P, Rifon Roca JJ, Cassaday RD, Boll B, Rijneveld A, Abdul-Hay M, Huguet F, Cluzeau T, Diaz MT, Vucinic V, Gonzalez-Campos J, Rambaldi A, Schwartz S, Berthon C, Hernandez-Rivas JM, Gordon PR, Bruggemann M, Hamidi A, Chen Y, Wong HL, Panwar B, Katlinskaya Y, Markovic A, Kantarjian H. Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia. Am J Hematol. 2024 Apr;99(4):586-595. doi: 10.1002/ajh.27227. Epub 2024 Feb 5.