Blinatumomab: Blinatumomab will be administered as a subcutaneous (SC) injection.
Study summary
The Phase I part of the study aims to evaluate the safety, efficacy, and tolerability of subcutaneous (SC) blinatumomab for treatment of Relapsed or Refractory B cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL), to determine the maximum tolerated dose (MTD), and recommended phase 2 dose(s) (RP2D) of SC administered blinatumomab.
The Phase II part of the study will evaluate the safety, efficacy, and tolerability of SC blinatumomab for treatment of R/R B-ALL and Minimum Residual Disease Positive (MRD+) B-ALL in participants 12 years old and greater. It will also conduct a clinical pharmacokinetic (PK) evaluation of SC1 and SC2 blinatumomab formulations.
Eligibility
Sex
ALL
Min age
12 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Ph-IIC, Dose Escalation and Dose Expansion: Aged 18 years or older (or same or greater than legal age within the country if it is older than 18 years).
* Ph-IIRa and Ph-IIMa: Aged ≥ 17 years at time of informed consent.
* Ph-IIRb and Ph-IIMb: Age ≥ 12 years and \< 17 years at time of informed consent.
* Ph-IIR, Ph-IIC, Dose escalation, Dose Expansion: Participants with R/R B-precursor ALL.
* Relapsed or Refractory B-precursor ALL at any time after first salvage therapy.
* Relapsed B-precursor ALL at any time after allogenic hematopoietic stem cell transplant (HSCT).
* Ph-IIR, Ph-IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the Bone Marrow per local assessment.
* Ph-IIM: B-precursor ALL and bone marrow blasts (BMB) ≥ 0.01% and \< 5% per local assessment.
* Ph-IIM: Availability of an appropriate archival BM specimen from initial or relapse diagnosis and the screening BM sample.
* Participants aged ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
* Participants aged 16 to \< 18 years old: Karnofsky Performance Score ≥ 50%.
* Participants aged \< 16 years old: Lansky Performance Score ≥ 50%.
* Any Ph+ participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
* Ph-IIM: BM function as follows:
* Absolute Neutrophil Count (ANC) ≥ 500/μL
* Platelet count ≥ 50 000/μL (transfusion permitted)
* Hemoglobin level ≥ 9 g/dL (transfusion permitted)
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. If CSF leukemia is present subjects will have to receive intrathecal therapy and have documented negative CSF prior to enrolling.
* History or presence of clinically relevant CNS pathology (excluding headache) 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.
* For Ph-IIM only: Current EM disease or presence of circulating leukemia blasts.
* Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
* Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication.
* 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 (with demonstrated continued CD19+ expression), if treatment ended more than 4 weeks prior to start of protocol 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: Pregnant or breastfeeding or planning to become pregnant or donate eggs, or 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 outcome measure(s)
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 TEAEs — 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 and Phase 2 Ph-IIR cohort: Number of participants who achieve complete remission (CR) / complete remission with partial hematological recovery (CRh) — Up to 10 weeks
Phase 2 Ph-IIC cohort: Maximum concentration (Cmax) of blinatumomab SC1 and SC2 — Up to approximately 4 weeks
Phase 2 Ph-IIC cohort: Average concentration (Cavg) of blinatumomab SC1 and SC2 — Up to approximately 4 weeks
Phase 2 Ph-IIC cohort: Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2 — Up to approximately 4 weeks
Phase 2 Ph-IIC cohort: Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2 — Up to approximately 4 weeks
Phase 2 Ph-IIM cohort: Number of participants who achieve CR with MRD-negative response — Up to 10 weeks
Trial sites (109)
Facility
City
Region
Status
University of California San Francisco Fresno at Community Cancer Institute
Clovis
California
City of Hope National Medical Center
Duarte
California
University of Illinois Chicago
Chicago
Illinois
Johns Hopkins University
Baltimore
Maryland
C.S. Mott Children's Hospital - University of Michigan
Ann Arbor
Michigan
Roswell Park Comprehensive Cancer Center
Buffalo
New York
New York University Grossman School of Medicine and New York University Langone Hospitals
New York
New York
Albert Einstein College of Medicine - Montefiore Medical Center
The Bronx
New York
Childrens Hospital of Philadelphia
Philadelphia
Pennsylvania
St Jude Childrens Research Hospital
Memphis
Tennessee
University of Texas MD Anderson Cancer Center
Houston
Texas
Fred Hutchinson Cancer Center
Seattle
Washington
The Medical College of Wisconsin
Milwaukee
Wisconsin
Hospital Italiano de Buenos Aires
Ciudad Autonoma de Buenos Aires
Buenos Aires
Sanatorio Allende
Córdoba
Córdoba Province
Instituto Alexander Fleming
Buenos Aires
Argentina
Cemic - Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno
Ciudad Autonoma Buenos Aires
Argentina
Sydney Childrens Hospital
Randwick
New South Wales
Westmead Hospital
Westmead
New South Wales
Queensland Childrens Hospital
South Brisbane
Queensland
Royal Adelaide Hospital
Adelaide
South Australia
Monash Medical Centre
Clayton
Victoria
Austin Health, Austin Hospital
Heidelberg
Victoria
The Alfred Hospital
Melbourne
Victoria
Perth Childrens Hospital
Nedlands
Western Australia
Universitaetsklinikum Allgemeines Krankenhaus Wien
Vienna
Austria
Centre Hospitalier Universitaire-Universite Catholique de Louvain Namur-Site Godinne
Yvoir
Belgium
Hospital Sirio Libanes Brasilia
Brasília
Federal District
Instituto Medicina Integral Imip
Recife
Pernambuco
Hosp de Clinicas de Porto Alegre
Porto Alegre
Rio Grande do Sul
Fundacao Amaral Carvalho
Jaú
São Paulo
Hosp Clin Fac Med Ribeirao Preto Usp
Ribeirão Preto
São Paulo
Instituto Onco Ped Graac Unifesp
São Paulo
São Paulo
Arthur J E Child Comprehensive Cancer Centre
Calgary
Alberta
University of Alberta
Edmonton
Alberta
Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
Vancouver
British Columbia
The Hospital for Sick Children
Toronto
Ontario
Princess Margaret Cancer Centre
Toronto
Ontario
Beijing Childrens Hospital, Capital Medical University
Beijing
Beijing Municipality
Fujian Medical University Union Hospital
Fuzhou
Fujian
+ 69 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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