A phase 1/2 study of subcutaneous blinatumomab administration in adults with R/R B-A

Phase 1

• Conditions: MedDRA version: 21.0Level: LLTClassification code 10000844Term: Acute lymphoblastic leukaemiaSystem Organ Class: 100000004864; Adults with relapsed or refractory B-precursor ALL (R/R B-ALL); MedDRA version: 21.0Level: LLTClassification code 10063621Term: Acute lymphoblastic leukaemia recurrentSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-004780-52-NL
• Lead Sponsor: Amgen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-04-04
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 245

Inclusion Criteria

Subjects are eligible to be included in the study only if all of the following criteria apply:
101 Subject has provided informed consent prior to initiation of any study specific activities/procedures and/or the subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent.
111 Subjects enrolled in SC1 and SC2 comparison cohort (Ph-IIC) must provide consent to participate in the additional PK sample collection requirements.
102 Age = 18 years at time of informed consent
Disease status: All subjects must fulfill at least 1 of inclusion criteria 103, 104, or 105 for eligibility.
For Ph-IIM cohort (subjects with MRD+ ALL [phase 2]) only: Subjects will be eligible for Ph-IIM if they have B-ALL and meet the MRD criteria defined in inclusion criterion #109 below. With the exception of disease status criteria (ie, inclusion criteria #103, #104, #105, #106), Ph-IIM cohort subjects must satisfy all other inclusion criteria to be eligible.
103 Subjects 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 achievement of first 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
104 Relapsed or Refractory at any time after first salvage therapy
105 Relapse at any time after allogenic HSCT.
106 Greater than or equal to 5% blasts in the BM. (Exception: Isolated Non CNS extramedullary disease [EMD]).
107 Eastern Cooperative Oncology Group (ECOG) Performance Status = 2.
108 Subjects with relapse or refractory B Cell ALL Ph+ disease and that are intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
109 For subjects in the MRD cohorts only (cohort Ph-IIM), BMB must be <5% and =0.1%. This will replace inclusion criterion #106 for subjects in this cohort
112 Subjects with Isolated (< 5% BMB) Non CNS Extra Medullary Disease (EMD) are eligible in phase 2 cohorts Ph-IIR and Ph-IIM only.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion Criteria

Disease Related
- Active ALL in the CNS. Presence of > 5 white blood cells (WBC) per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present (confirmed by CSF analysis) 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.
Other Medical Conditions
- History or presence of clinically relevant CNS pathology or event 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 ICANS from prior CD19 CART or other T cell engager therapies.
- 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.
- Known hypersensitivity to blinatumomab or to any component of the product formulation.
- Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus.
- Symptoms and/or clinical signs and/or radiological and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol.
- History of malignancy other than ALL within 3 years prior to start of protocol-specified therapy except for:
Malignancy treated with curative intent and with no known active disease present for 3 years before enrollment and felt to be at low risk for recurrence by the treating physician.
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
Adequately treated cervical carcinoma in situ without evidence of disease.
Adequately treated breast ductal carcinoma in situ without evidence of disease.
Prostatic intraepithelial neoplasia without evidence of prostate cancer.

- 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 the exception of intrathecal chemotherapy and/or low dose maintenance therapy for example vinca alkaloids, mercaptopurine, methotrexate, or hydroxyurea (any low dose chemotherapy as stated above must be discontinued before starting pre-phase) or pre-phase chemotherapy and/or dexamethasone.
- Immunotherapy (eg, rituximab, alemtuzumab) within 4 weeks before start of protocol-specified therapy. Prior failed CD19 directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed (with demonstrated continued CD19+ expression), if treatment ended > 4 weeks prior to start of protocol therapy. and no prior CNS complications (see exclusion criteria 202).
Prior/Concurrent Clinical Study Experience
- Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study. Other investigational studies are not permitted while participating in this study.
Diagnostic Assessments
- Abnormal screening laboratory values as defined below:
Total bilirubin >3.0 mg/dL prior to start of treatment (unless related to Gilbert’s or Meulengracht disease)
Estimated Creatinine clearance < 60 mL/min
Other Exclusions
- Female subject is pregnant or breastfe

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified