A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients

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)

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.

Study Overview

• Status: Recruiting
• Conditions: B Cell Precursor Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Blinatumomab

• Study Type: Interventional
• Enrollment (Estimated): 125
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Health, Austin Hospital
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital
• Austria
  • Wien, Austria, 1090
    • Completed
    • Universitaetsklinikum Allgemeines Krankenhaus Wien
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Recruiting
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 2P4
      • Recruiting
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Recruiting
      • Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
• France
  • Lille, France, 59000
    • Recruiting
    • Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez
  • Nice cedex 3, France, 06202
    • Recruiting
    • Centre Hospitalier Universitaire de Nice
  • Paris, France, 75012
    • Recruiting
    • Hopital Saint Antoine
  • Toulouse cedex 9, France, 31059
    • Recruiting
    • Institut Universitaire du Cancer Toulouse Oncopole
• Germany
  • Berlin, Germany, 12200
    • Recruiting
    • Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin
  • Jena, Germany, 07747
    • Recruiting
    • Universitaetsklinikum Jena
  • Koeln, Germany, 50937
    • Recruiting
    • Universitaetsklinikum Koeln
  • Leipzig, Germany, 04103
    • Recruiting
    • Universitaetsklinikum Leipzig
  • Tuebingen, Germany, 72076
    • Completed
    • Universitaetsklinikum Tuebingen
  • Ulm, Germany, 89081
    • Recruiting
    • Universitatsklinikum Ulm
• Italy
  • Bergamo, Italy, 24127
    • Recruiting
    • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant Orsola
  • Brescia, Italy, 25123
    • Recruiting
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Milano, Italy, 20132
    • Terminated
    • IRCCS Ospedale San Raffaele
  • Roma, Italy, 00161
    • Recruiting
    • Azienda Ospedaliera Policlinico Umberto I
• Japan
  • Akita
    • Akita-shi, Akita, Japan, 010-8543
      • Recruiting
      • Akita University Hospital
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Fukushima
    • Fukushima-shi, Fukushima, Japan, 960-1295
      • Recruiting
      • Fukushima Medical University Hospital
  • Kanagawa
    • Yokohama-shi, Kanagawa, Japan, 232-0024
      • Recruiting
      • Yokohama City University Medical Center
• Netherlands
  • Rotterdam, Netherlands, 3015 CN
    • Recruiting
    • Erasmus Medisch Centrum
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de octubre
  • Andalucía
    • Sevilla, Andalucía, Spain, 41013
      • Recruiting
      • Hospital Universitario Virgen del Rocio
  • Castilla León
    • Salamanca, Castilla León, Spain, 37007
      • Recruiting
      • Complejo Asistencial Universitario de Salamanca Hospital Universitario de Salamanca
  • Cataluña
    • Badalona, Cataluña, Spain, 08916
      • Recruiting
      • Institut Catala d Oncologia Badalona Hospital Universitari Germans Trias i Pujol
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Recruiting
      • Hospital Clínico Universitario de Valencia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra
• Turkey
  • Istanbul, Turkey, 34214
    • Recruiting
    • Bagcilar Medipol Mega Universite Hastanesi
  • Izmir, Turkey, 35575
    • Recruiting
    • Izmir Ekonomi Universitesi Medical Point Hastanesi
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University Langone Health
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Recruiting
      • University of Washington
    • Seattle, Washington, United States, 98109-1023
      • Completed
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 years or older.

• 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 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 treatment.

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Phase: Blinatumomab Subcutaneous Formulation 1 (SC1); Cohorts of at least 3 participants each will be treated with escalating doses of bilinatumomab to determine the maximum tolerated dose (MTD). The MTD will be defined as the dose for which the estimate of the toxicity rate from an isotonic regression (Yan et al, 2017) is closest to the target toxicity rate. Safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy will be assessed.	Drug: Blinatumomab; Blinatumomab will be administered as a subcutaneous (SC) injection.; Other Names: AMG 103; Blincyto®
Experimental: Dose Expansion Phase: Blinatumomab SC1; Up to 4 cohorts of participants with R/R B-ALL will be enrolled to the preliminary recommended phase 2 dose (RP2D) and schedule determined from dose escalation phase. Each cohort will aim to further assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy.	Drug: Blinatumomab; Blinatumomab will be administered as a subcutaneous (SC) injection.; Other Names: AMG 103; Blincyto®
Experimental: Ph-IIC: Clinical PK Evaluation of SC Blinatumomab Formulations; 1 cohort of participants will be enrolled into the Ph-IIC arm. The clinical PK evaluation cohort (Ph-IIC) will be conducted to compare the PK of SC1 and SC2 formulations at the RP2D determined from the dose expansion phase, in participants with R/R B-ALL.	Drug: Blinatumomab; Blinatumomab will be administered as a subcutaneous (SC) injection.; Other Names: AMG 103; Blincyto®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose Escalation Phase: Number of participants who experience dose limiting toxicities (DLTs)	Up to 29 days
Dose Escalation Phase: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)	Up to approximately 28 weeks
Dose Escalation Phase: Number of participants who experience one or more serious TEAEs	Up to approximately 28 weeks
Dose Escalation Phase: Number of participants who experience one or more treatment-related treatment-emergent adverse events	Up to approximately 28 weeks
Dose Escalation Phase: Number of participants who experience one or more adverse events (AEs)	Up to approximately 28 weeks
Dose Expansion Phase (R/R B-ALL): Number of participants who achieve complete remission (CR)	Up to 68 days
Dose Expansion Phase (R/R B-ALL): Number of participants who achieve complete remission with partial hematological recovery (CRh)	Up to 68 days
Phase 2 Ph-IIC: Maximum concentration (Cmax) of blinatumomab SC1 and SC2	Up to approximately 4 weeks
Phase 2 Ph-IIC: Average concentration (Cavg) of blinatumomab SC1 and SC2	Up to approximately 4 weeks
Phase 2 Ph-IIC: Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2	Up to approximately 4 weeks
Phase 2 Ph-IIC: Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2	Up to approximately 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Dose Escalation Phase: Minimum concentration over the dosing interval (Cmin) of blinatumomab	Up to approximately 28 weeks
Dose Expansion Phase: Cmin of blinatumomab	Up to approximately 28 weeks
Dose Expansion Phase: Cmax of blinatumomab	Up to approximately 28 weeks
Dose Expansion Phase: Tmax of blinatumomab	Up to approximately 28 weeks
Dose Expansion Phase: AUC of blinatumomab	Up to approximately 28 weeks
Dose Escalation Phase: Cmax of blinatumomab	Up to approximately 28 weeks
Dose Escalation Phase: Tmax of blinatumomab	Up to approximately 28 weeks
Dose Escalation Phase: AUC of blinatumomab	Up to approximately 28 weeks
Dose Escalation Phase and Phase 2 (Ph-IIC cohort): Number of participants who achieve CR/CRh	Up to 68 days
Dose Escalation, Dose Expansion, and Ph-IIC: Number of participants with incidence of anti-blinatumomab antibody formation	Up to approximately 28 weeks
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)	Up to 68 days
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Overall survival (OS)	Up to approximately 28 weeks
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Duration of complete response	Up to approximately 28 weeks
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more TEAEs	Up to approximately 28 weeks
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more serious treatment-emergent adverse event	Up to approximately 28 weeks
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more treatment-related treatment-emergent adverse events	Up to approximately 28 weeks
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more AEs	Up to approximately 28 weeks
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)	Baseline (Day 1) up to approximately 28 weeks
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Change from baseline of quality of life as assessed by the EORTC QLQ-C30	Baseline (Day 1) up to approximately 28 weeks

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Estimated): November 23, 2026
• Study Completion (Estimated): September 21, 2028

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Blinatumomab; R/R B-ALL; Blincyto®; AMG 103; Acute lymphoblastic leukemia (ALL)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: 20180257; 2019-004780-52 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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