A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients
- Conditions
- B Cell Precursor Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT04521231
- Lead Sponsor
- Amgen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 125
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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:
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Either refractory to primary induction therapy or refractory to at least 1 salvage therapy OR
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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
-
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Relapsed or Refractory at any time after first salvage therapy.
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Relapse at any time after allogenic hematopoietic stem cell transplant (HSCT).
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Greater than or equal to 5% blasts in the Bone Marrow (Exception: Isolated Non-central nervous system (CNS) extramedullary disease [EMD]).
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Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
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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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion Phase: Blinatumomab SC1 Blinatumomab 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. Dose Escalation Phase: Blinatumomab Subcutaneous Formulation 1 (SC1) Blinatumomab 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. Ph-IIC: Clinical PK Evaluation of SC Blinatumomab Formulations Blinatumomab 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.
- Primary Outcome Measures
Name Time Method 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) of Interest (AEIs) 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
Name Time Method 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 AEIs 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 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 Escalation Phase: Minimum concentration over the dosing interval (Cmin) 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: 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
Trial Locations
- Locations (43)
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Andalucía, Spain
Complejo Asistencial Universitario de Salamanca Hospital Universitario de Salamanca
🇪🇸Salamanca, Castilla León, Spain
Institut Catala d Oncologia Badalona Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Cataluña, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Comunidad Valenciana, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Bagcilar Medipol Mega Universite Hastanesi
🇹🇷Istanbul, Turkey
Izmir Ekonomi Universitesi Medical Point Hastanesi
🇹🇷Izmir, Turkey
New York University Grossman School of Medicine and New York University Langone Hospitals
🇺🇸New York, New York, United States
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Arthur J E Child Comprehensive Cancer Centre
🇨🇦Calgary, Alberta, Canada
University of Alberta
🇨🇦Edmonton, Alberta, Canada
Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
🇨🇦Vancouver, British Columbia, Canada
Universitaetsklinikum Augsburg
🇩🇪Augsburg, Germany
Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin
🇩🇪Berlin, Germany
Universitaetsklinikum Jena
🇩🇪Jena, Germany
Universitaetsklinikum Koeln
🇩🇪Koeln, Germany
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
Universitatsklinikum Ulm
🇩🇪Ulm, Germany
Azienda Socio Sanitaria Territoriale Papa Giovanni xxiii
🇮🇹Bergamo, Italy
IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant Orsola
🇮🇹Bologna, Italy
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
🇮🇹Brescia, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedaliera Policlinico Umberto I
🇮🇹Roma, Italy
Akita University Hospital
🇯🇵Akita-shi, Akita, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Chiba, Japan
Austin Health, Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Universitaetsklinikum Allgemeines Krankenhaus Wien
🇦🇹Wien, Austria
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
🇫🇷Lille, France
Centre Hospitalier Universitaire de Nice
🇫🇷Nice cedex 3, France
Hopital Saint Antoine
🇫🇷Paris, France
Institut Universitaire du Cancer Toulouse Oncopole
🇫🇷Toulouse cedex 9, France
Fukushima Medical University Hospital
🇯🇵Fukushima-shi, Fukushima, Japan
Yokohama City University Medical Center
🇯🇵Yokohama-shi, Kanagawa, Japan