BridgeMD
A phase 1/2 study of subcutaneous blinatumomab administration in adults and adolescents with R/R and MRD+ B-ALL
EU CTIS ID: 2023-506136-32-00
What this study is testing
Dose escalation - Evaluate the safety and tolerability of subcutaneous (SC) blinatumomab for treatment of Relapsed or Refractory B cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL) Dose escalation - Determine the maximum tolerated dose (MTD) and preliminary recommended phase 2 dose(s) (RP2D) of SC administered blinatumomab Dose Expansion - Evaluate the efficacy of SC blinatumomab Phase 2 Ph-IIC (Subcutaneous Formulation 1 [SC1] and Subcutaneous Formulation 2 [SC2] Cohorts)a,b - Evaluate the PK following SC administration of SC1 and SC2 blinatumomab formulations Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - Evaluate the efficacy of SC blinatumomab Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) - Evaluate the efficacy of SC blinatumomab
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 101 Subject has provided informed consent before initiation of any study specific activities/procedures and/or the subject’s legally authorized 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 or the subject’s legally authorized representative has provided informed consent when the participant is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines before any study-specific activities/procedures being initiated.
- (Disease History) Ph-IIR, Ph IIC, Dose escalation, Dose Expansion: subjects must fulfill at least 1 of inclusion criteria 103, 104, or 105 for eligibility. 105 Relapsed B precursor ALL at any time after allogeneic HSCT.
- (Disease Status) 106 Ph IIR, Ph IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the BM per local assessment.
- 107 Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
- 114 (Age requirement) Ph-IIRa and Ph-IIMa: Age ≥ 17 years at time of informed consent.
- 113 (Age requirement) Ph-IIRb and Ph-IIMb: Age ≥ 12 years and <17 years at time of informed consent.
You likely can't join if
- 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.
- Isolated EM disease For Ph-IIM only: Current EM disease or presence of circulating leukemia blasts
- Testicular leukemia
- Cancer chemotherapy within 2 weeks before the start of protocolspecified 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 prephase) 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).
- Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives since ending treatment on another investigational device or drug study. Other investigational or observational studies are not permitted while participating in this study
See the full eligibility criteria
Who can join
- 101 Subject has provided informed consent before initiation of any study specific activities/procedures and/or the subject’s legally authorized 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 or the subject’s legally authorized representative has provided informed consent when the participant is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines before any study-specific activities/procedures being initiated.
- (Disease History) Ph-IIR, Ph IIC, Dose escalation, Dose Expansion: subjects must fulfill at least 1 of inclusion criteria 103, 104, or 105 for eligibility. 105 Relapsed B precursor ALL at any time after allogeneic HSCT.
- (Disease Status) 106 Ph IIR, Ph IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the BM per local assessment.
- 107 Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
- 114 (Age requirement) Ph-IIRa and Ph-IIMa: Age ≥ 17 years at time of informed consent.
- 113 (Age requirement) Ph-IIRb and Ph-IIMb: Age ≥ 12 years and <17 years at time of informed consent.
- 107 (Performance Status Requirement) Age ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
- 115 (Performance Status Requirement) Age 16 to <18 years old: Karnofsky Performance Score ≥ 50%
- 116 (Performance Status Requirement) Age < 16 years old: Lansky Performance Score ≥ 50%
- (Disease Status) 117 Ph IIM: Subjects must have B precursor ALL and BMB ≥ 0.01% and <5% per local assessment.
- (Disease Status) 118 Ph IIM: Availability of an appropriate archival bone marrow specimen from initial or relapse diagnosis and the screening BM sample.
- (Disease Status) 108 A Ph+ subject intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) is eligible.
- (Bone Marrow Function) 119 Ph-IIM: Bone marrow function as defined below: • Absolute Neutrophil Count (ANC) ≥500/µL • Platelet count ≥50,000/ µL (transfusion permitted) • Hemoglobin level ≥ 9g/dL (transfusion permitted)
- (Other) 120 Ph-IIRb extended cohort: Weight <45 kg at screening
- 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.
- 111 Ph-IIC only: Subject enrolled in SC1 and SC2 comparison cohort (Ph-IIC) must provide consent to participate in the additional PK sample collection requirements.
- 102 (Age requirement) Ph-IIC, Dose Escalation and Dose Expansion: Age ≥ 18 years (or ≥ legal age within the country if it is older than 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.
- (Disease History) Ph-IIR, Ph IIC, Dose escalation, Dose Expansion: subjects must fulfill at least 1 of inclusion criteria 103, 104, or 105 for eligibility. 103 Subjects with B precursor ALL with any of the following: • Either refractory to primary induction therapy or relapse after 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 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.
- (Disease History) Ph-IIR, Ph IIC, Dose escalation, Dose Expansion: subjects must fulfill at least 1 of inclusion criteria 103, 104, or 105 for eligibility. 104 Relapsed or Refractory B precursor ALL at any time after first salvage therapy
What rules you out
- 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.
- Isolated EM disease For Ph-IIM only: Current EM disease or presence of circulating leukemia blasts
- Testicular leukemia
- Cancer chemotherapy within 2 weeks before the start of protocolspecified 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 prephase) 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).
- Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives since ending treatment on another investigational device or drug study. Other investigational or observational studies are not permitted while participating in this study
- Dose Escalation, Dose Expansion, Ph IIC: Abnormal screening laboratory values as defined below: - Total bilirubin more than 3.0 mg/dL prior to start of treatment (unless related to Gilbert’s or Meulengracht disease) - Estimated Creatinine clearance less than 60 mL/min.
- Female subject is pregnant or breastfeeding or planning to become pregnant or donate eggs or breastfeed during treatment and for an additional 96 hours after the last dose of investigational product (SC blinatumomab)
- Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 96 hours after the last dose of investigational product (SC blinatumomab).
- Female subjects of childbearing potential with a positive pregnancy test assessed during Screening by a serum pregnancy test and/or urine pregnancy test.
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator’s awareness. Completion of patient reported outcomes questionnaires is not required and will not be prohibitive to enrollment in case patient has intellectual disability or cognitive impairment or in case instrument is unavailable in subject’s language
- 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 (excluding headache) including ICANS from prior CART or other T cell engager therapies.
- 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
- Ph IIR and Ph IIM: 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 < 30 mL/min per the Cockcroft-Gault equation for subjects ≥ 18 years and estimated Glomerular Filtration Rate (eGFR)< 30 mL/min per 1.73 m2 per the Revised Schwartz equation for subjects 12 to < 18 years.
- 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
The study team makes the final eligibility decision.
Where it's taking place
- Korea, Republic of
- Argentina
- United Kingdom
- Israel
- Japan
- Brazil
- Mexico
- Australia
- China
- Canada
- Hong Kong
- United States
- Turkey
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Korea, Republic of; Argentina; United Kingdom; Israel; Japan; Brazil and 7 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.