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

Amgen

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: B Cell Precursor Acute Lymphoblastic Leukemia

Treatments: Drug: Blinatumomab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04521231

20180257

2023-506136-32 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 125 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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125 participants in 3 patient groups

Dose Escalation Phase: Blinatumomab Subcutaneous Formulation 1 (SC1)

Experimental group

Description:

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.

Treatment:

Drug: Blinatumomab

Dose Expansion Phase: Blinatumomab SC1

Experimental group

Description:

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.

Treatment:

Drug: Blinatumomab

Ph-IIC: Clinical PK Evaluation of SC Blinatumomab Formulations

Experimental group

Description:

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.

Treatment:

Drug: Blinatumomab