Clinical trial NCT06649006: Study to Investigate Intravenous Blinatumomab in Japanese Adult Participants With Newly Diagnosed Philadelphia-negative B-precursor Acute Lymphoblastic Leukemia (B-ALL)
Official title: A Phase 1b Open-label Study to Investigate Safety, Tolerability and Pharmacokinetics of Intravenous Blinatumomab in Japanese Adult Subjects With Newly Diagnosed Philadelphia-negative B-precursor Acute Lymphoblastic Leukemia (B-ALL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: B-precursor Acute Lymphoblastic Leukemia
Keywords: Leukemia
Blincyto®
Blinatumomab
B-precursor Acute Lymphoblastic Leukemia
B-ALL
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-10-18
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main objective of the study is to evaluate safety and tolerability of blinatumomab in adult Japanese participants with newly diagnosed B-ALL.


Eligibility criteria: Inclusion Criteria:

* Japanese adult participants ≥ 18 years and ≤ 70 years at enrollment.
* Participant should have newly diagnosed B-cell precursor (BCP)
* Philadelphia-negative ALL in CR/CRh after induction/consolidation therapy with any MRD (+ or -).
* CR/CRh by the end of induction and 3 blocks of consolidation chemotherapy with ALL MRD2008/2019/2023 protocol regimen or 3 blocks of Hyper-CVAD.
* Bone marrow function as defined below:

  * Absolute neutrophil count (ANC) (Neutrophils) ≥500/μL
  * Platelets ≥50.000/μL (transfusion permitted)
* Adequate renal and hepatic function:

  * Total bilirubin (TBL) ≤ 2.0 x upper limit of normal (ULN) (ULN; unless Gilbert's Disease or if liver involvement with leukemia)
  * Creatinine clearance ≥50 mL/min/1.73 m\^2
* Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2.

Exclusion Criteria:

Disease Related • Current infiltration of cerebrospinal fluid (CSF) by ALL. If screening CSF demonstrates leukemic blasts, participants must receive intrathecal treatment and demonstrate negative CSF before enrollment and starting blinatumomab infusion.

Other Medical Conditions

* History of relevant central nervous system (CNS) pathology or current relevant CNS pathology (e.g., seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, or coordination or movement disorders).
* Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
* Active uncontrolled infection requiring therapy.
* History of other malignancy within the past 3 years, with the following exceptions:

  * 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 nonmelanoma 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.
  * Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.

Prior/Concomitant Therapy

* Systemic cancer chemotherapy within 2 weeks prior to study treatment (except for intrathecal prophylaxis)
* Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus. In Japan, follow the JSH Guidelines for the Management of Hepatitis B Virus Infection version 4 (The Japan Society of Hepatology, 2022) for the screening of Hepatis B virus infection.
* Radiotherapy within 4 weeks prior to study treatment.

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(ies). This does not apply to other investigational procedures or participation in observational research studies while participating in this study are excluded.

Other Exclusions

* Participants of childbearing potential unwilling to use protocol-specified method of contraception during treatment and for an additional 48 hours after the last dose of blinatumomab.
* Participants who are breastfeeding or who plan to breastfeed while on study through 48 hours after the last dose of blinatumomab.
* Participants planning to become pregnant or donate eggs while on study through 48 hours after the last dose of blinatumomab.
* Participants of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive urine or serum pregnancy test.
* Participant has known hypersensitivity to blinatumomab or to any component of the product formulation.
* Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (e.g., Clinical Outcome Assessments) to the best of the participant and investigator's knowledge.
* History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety, or interfere with the study evaluation, procedures, or completion.

Primary outcomes:
measure: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 31 weeks
measure: Number of Participants Experiencing Adverse Events of Interest (EOI)
timeFrame: Up to 31 weeks
Secondary outcomes:
measure: Steady-state Concentration (Css) of Blinatumomab
timeFrame: Day 1 pre-dose, 2 and 6 hours post-dose on Day 1, Day 2, Day 3, Day 29
measure: Clearance (CL) of Blinatumomab
timeFrame: Day 1 pre-dose, 2 and 6 hours post-dose on Day 1, Day 2, Day 3, Day 29
measure: Number of Participants Achieving Minimal Residual Disease (MRD) After Each Cycle of Blinatumomab
timeFrame: Cycles 1-4: Day 29 (each cycle is 6 weeks)
measure: Number of Participants Achieving Hematologic Complete Remission (CR)
timeFrame: Cycles 1-4: Day 29 (each cycle is 6 weeks)
measure: Number of Participants Achieving Hematologic CR with Partial Peripheral Count Recovery (CRh)
timeFrame: Cycles 1-4: Day 29 (each cycle is 6 weeks)
Other outcomes:
Locations:
city: Akita-shi
country: Japan
facility: Akita University Hospital
state: Akita
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital
state: Fukuoka
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Fukushima-shi
country: Japan
facility: Fukushima Medical University Hospital
state: Fukushima
city: Kanazawa-shi
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa
city: Yamagata-shi
country: Japan
facility: Yamagata University Hospital
state: Yamagata
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: