Newly Diagnosed Philadelphia (Ph)-Negative B-cell Precursor Acute Lymphoblastic Leukemia (ALL)
Conditions
Interventions
- Experimental: Safety Run-in: Blinatumomab alternating with low-intensity chemotherapy
The safety run-in will be performed prior to initiating the phase 3 randomized part of the study. This safety r
Sponsors
Oda Kazunori
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age >= 55 years at the time of informed consent. OR Age 40 to 10 x upper limit of normal (ULN) (liver cirrhosis must be confirmed by biopsy) - body mass index (BMI) >= 40 combined with relevant comorbidities such as metabolic syndrome - Any further combination of documented severe comorbidities that the investigator judges to be incompatible with administering an intensive pediatric based, adult adapted standard chemotherapy regimen but still compatible with the suggested protocol for older participants in both the experimental and the SOC arm. The participant history will be reviewed by the medical monitor during screening to determine enrollment acceptability based on a standard list with types of comorbidities allowed. 2. Participants with newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL) 3. Eastern Cooperative Oncology Group (ECOG) performance status = 50 mL/min/1.73 m^2 - liver function: total bilirubin 10 x ULN (liver cirrhosis must be confirmed by biopsy) - cardiac: left ventricular ejection fraction (LVEF) >= 50% and no clinically significant, uncontrolled, or active cardiovascular disease (eg, myocardial infarction or stroke within 3 months). Consult with medical monitor as needed.
Exclusion criteria
Exclusion criteria: 1. Active central nervous system (CNS) leukemia (i.e., CNS 3 leukemia, confirmed by lumbar puncture) not resolved with IT chemotherapy during screening. 2. 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 Note: History of other malignancy (eg, multiple myeloma) treated with immunomodulatory drugs (eg, lenalidomide, thalidomide) in the past 3 years is an exclusion. - 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 - Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ 3. 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, or psychiatric conditions that preclude the use of high dose of corticosteroids 4. Current autoimmune disease or history of autoimmune disease with potential CNS involvement 5. Known infection with human immunodeficiency virus (HIV) 6. Known infection with chronic or active infection with hepatitis B (eg, hepatitis b surface [HBs] antigen reactive or quantifiable hepatitis b virus [HBV] viral load) or hepatitis C virus (HCV) (eg, HCV RNA [qualitative] is detected). Active hepatitis B and C based on the following results: - positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B) - negative HepBsAg and positive for hepatitis B core antibody: negative HBV DNA by PCR result is necessary to enroll. - positive Hepatitis C virus antibody (HepCAb): negative hepatitis C virus RNA by PCR result is necessary to enroll. 7. Participant with symptoms and/or clinical signs and/or radiographic and/or sonographic signs that indicate an acute or uncontrolled chronic infection. 8. Cancer chemotherapy for this newly diagnosed B cell ALL before the start of protocol-required therapy with the exception of IT chemotherapy or optional pre-phase (debulking) chemotherapy. Radiation to a spot lesion such as chloroma or lytic lesion of bone or vertebrae for pain or vertebral stabilization is allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety run-in: Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) [Time Frame: Up to approximately 5 years] Number and percentage of participants who experience one or more TEAE, serious TEAE, treatment-related adverse events, and adverse events of interest. 2. Phase 3: Event-free Survival (EFS) [Time Frame: Up to approximately 5 years] Time from randomization (enrollment) until treatment failure, relapse or death from any cause, whichever is earlier. Treatment failure is defined as not achieving a hematological complete CR with MRD response = 10^-3), whichever occurs earlier, in participants with prior achievement of hematologic CR with MRD response <10^-4. Participants without an event will be censored at their last evaluable disease assessment date. 3. Phase 3: Overall Survival (OS) [Time Frame: Up to approximately 5 years] OS is defined as time from randomization (enrollment) until death due to any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety run-in: Complete Remission (CR) Rate by the End of Initial Disease Assessment Period [Time Frame: Baseline to Week 14] 2. Safety run-in: Minimal Residual Disease (MRD) Response by the End of Initial Disease Assessment Period [Time Frame: Baseline to Week 14] MRD response is defined as the percentage of participants who achieve a response of = 10^-3 and MRD>=10^-4. Participants without an event will be censored at their last evaluable disease assessment date. 5. Safety run-in: Steady State Concentration (Css) of Blinatumomab [Time Frame: Up to approximately 34 weeks] 6. Safety run-in: Clearance (CL) of Blinatumomab [Time Frame: Up to approximately 34 weeks] 7. Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Fatigue Score [Time Frame: Baseline to Week 14] Fatigue score will be measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue - Short Form 7a. 8. Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Pain Score [Time Frame: Baseline to Week 14] Pain score will be measured by Brief Pain Inventory - Short Form (BPI-SF); Item 3: pain at its worst in the last 24 hours. 9. Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Global Health Status [Time Frame: Baseline to Week 14] Global health status will be measured by the Quality of Life Questionnaire (QLQ)-C30 global health status quality of life scale. 10. Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Physical Function [Time Frame: Baseline to Week 14] Physical function will be measured by the QLQ-C30 functional scale. 11. Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Nausea and Vomiting [Time Frame: Baseline to Week 14] Nausea and vomiting will be measured by the QLQ-C30 symptom scale. 12. Phase 3: Complete Remission (CR) Rate by the End of Initial Disease Assessment Period [Time Frame: Baseline to Week 14] 13. Phase 3: Minimal Residu | — |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Portugal, Romania, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactContact Local
Amgen K.K.
Outcome results
None listed