recentelijk gediagnosticeerde Philadelphia-negatieve precursor B-cel acute lymfoblastische leukemie Leukemia / Philadelphia negative (Ph[-]) B-cell precursor acute lymphoblastic leukaemia (ALL)
Conditions
Interventions
In the phase 3 portion of the study, after completing the screening period,
eligible subjects will be randomized 1:1 between the experimental arm
consisting of blinatumomab alternating with low-inte
Sponsors
Amgen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • 101 Subject has provided informed consent prior to initiation of any study specific activities/procedures. OR Where permitted by local law, 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. • 102 Age >= 55 years at the time of informed consent. OR Age 40 to 10 x ULN (liver cirrhosis must be confirmed by biopsy) o body mass index (BMI) >= 40 combined with relevant comorbidities such as metabolic syndrome o 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 subjects in both the experimental and the SOC arm. The subject history will be reviewed by the medical monitor during screening to determine enrollment acceptability based on a standard list with types of comorbidities allowed. • 103 Subjects with newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL) • 104 Eastern Cooperative Oncology Group (ECOG) performance status = 50 mL/min/1.73 m2 o liver function: total bilirubin 10 x ULN (liver cirrhosis must be confirmed by biopsy) o cardiac: left ventricular ejection fraction (LVEF) >= 50%
Exclusion criteria
Exclusion criteria: Disease Related • 201 Active CNS leukemia not resolved with IT chemotherapy during screening. Other Medical Conditions • 202 History of other malignancy within the past 3 years, with the following exceptions: o 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. o Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. o Adequately treated cervical carcinoma in situ without evidence of disease. o Adequately treated breast ductal carcinoma in situ without evidence of disease. o Prostatic intraepithelial neoplasia without evidence of prostate cancer. o Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ. • 203 Clinically relevant CNS pathology requiring treatment (eg, unstable epilepsy). • 204 Current autoimmune disease or history of autoimmune disease with potential CNS involvement • 219 Known infection with human immunodeficiency virus (HIV) • 220 Known infection with chronic or active 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: o Positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B) o Negative HepBsAg and positive for hepatitis B core antibody: negative HBV DNA by PCR result is necessary to enroll. o Positive Hepatitis C virus antibody (HepCAb): negative hepatitis C virus RNA by PCR result is necessary to enroll. • 221 Subject with symptoms and/or clinical signs and/or radiographic and/or sonographic signs that indicate an acute or uncontrolled chronic infection. Prior/Concomitant Therapy • 207 Cancer chemotherapy for this newly diagnosed B cell ALL before the start of protocol-required therapy with the exception of IT chemotherapy or pre-phase chemotherapy. Radiation to a spot lesion such as chloroma or lytic lesion of bone or vertebrae for pain or vertebral stabilization is allowed. Prior/Concurrent Clinical Study Experience • 208 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). Other investigational procedures while participating in this study are excluded. Other Exclusions • 209 Female subjects of childbearing potential unwilling to use protocol specified method of contraception (see Section 11.5) during treatment and for an additional 12 months after the last dose of protocol-required therapy. • 210 Female subjects who are breastfeeding or who plan to breastfeed while on study through 12 months after the last dose of protocol-required therapy. • 211 Female subjects planning to become pregnant while on study through 12 months after the last dose of protocol-required therapy. • 212 Female subjects of childbearing potential with a positive pregnancy test assessed at screening and/or assessed within 3 days prior to starting study chemotherapy treatment on day 1 by a highly sensitive urine or serum pregnancy test. • 223 Male subjects with a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • EFS: time from randomization until treatment failure, relapse, or death from any cause, whichever is earlier. Subjects without an event will be censored at their last evaluable disease assessment date. • OS: time from randomization until death due to any cause. Subjects alive will be censored at the date last known to be alive. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary • change from baseline to end of the initial disease assessment period in fatigue score measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue - Short Form 7a • change from baseline to end of the initial disease assessment period in pain score measured by Brief Pain Inventory - Short Form (BPI-SF); Item 3: pain at its worst in the last 24 hours • change from baseline to end of the initial disease assessment period in global health status measured by the QLQ-C30 global health status quality of life scale • change from baseline to end of the initial disease assessment period in physical function measured by the QLQ-C30 functional scale • change from baseline to end of the initial disease assessment period in nausea/vomiting measured by the QLQ-C30 symptom scale Secondary • CR by the end of the initial disease assessment period • MRD response = 10-3 and MRD >= 10-4. Subjects without an event will be censored at their last evaluable disease assessment date. • MRD level over time • treatment-emergent adverse events (TEAEs), serious TEAEs, treatment related adverse events, and adverse events of interest • CD19 positive relapse and CD19 negative relapse identified by flow cytometry or immunocytochemistry for bone marrow (mandatory) • CD19 positive relapse and CD19 negative relapse identified by flow cytometry or immunohistochemistry for cerebrospinal fluid (mandatory) • CD19 positive relapse and CD19 negative relapse for extramedullary sites other than cerebrospinal fluid (optional - if data is available) • lineage switch to acute myeloid leukemia (AML) • localization of relapse by clinical assessment • Mortality in CR • autologous and allogeneic HSCT in continuous first CR* • mortality in CR after autologous and allogeneic HSCT* • mortality in CR after autologous and allogeneic HSCT* • time to deterioration and time to improvements for fatigue score measured by PROMIS Fatigue - Short Form 7a • | — |
Countries
Netherlands
Outcome results
None listed