Pediatric Relapsed Acute Lymphoblastic Leukemia
Conditions
Interventions
Group A:venetoclax 240 mg/m2+ PVL chemotherapy
Group B-1:venetoclax360 mg/m2+PVL chemotherapy
Group B-2:venetoclax480 mg/m2+PVL chemotheraoy
Phase I escalation:venetoclax240/360480 mg/m2+PVL chemotheraoy
Sponsors
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Eligibility
Sex/Gender
All
Age
No minimum to 18 Years
Inclusion criteria
Inclusion criteria: 1. Diagnosis Relapsed or refractory B-cell precursor (Ph- and Ph+) or T-cell acute lymphoblastic leukemia >= 1% bone marrow disease as measured by flow cytometry, PCR, or next-generation sequencing. However, if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia with >= 5% blasts in the peripheral blood. (1) Patients with 1-4.99% bone marrow involvement must have disease confirmed in one of the following ways: an alternative minimal residual disease assay (e.g. flow cytometry and PCR or NGS), cytogenetic abnormality consistent with patients leukemia, FISH abnormality, or a second bone marrow with MRD >= 1% separated by 3-28 days. (2) Refractory disease is defined as residual leukemia >= 1% after at least 2 prior lines of frontline therapy with curative intent; 2. Age > 3 to 60%. The Lansky performance score should be used for participants = 16 years; 5. Participant has adequate organ function as defined by the following: (1) Direct bilirubin 1.5x the ULN. (2) Aspartate transaminase (AST) and alanine transaminase (ALT) = 60 mL/min/1.73 m^2. (4) Left ventricular ejection fraction >= 40% or shortening fraction >= 25%. 6. Patients must have fully recovered from the acute effects of all prior therapy (defined as resolution of all such toxicities to = 2 weeks; 8. Patients with Down Syndrome/ germline Trisomy 21 are eligible for Block 1 therapies but are ineligible for Block 2 therapy. Patients with Down Syndrome are off therapy after the response evaluation to Block 1.
Exclusion criteria
Exclusion criteria: 1. Known HIV infection or active hepatitis B (defined as hepatitis B surface antigen–positive) or C (defined as hepatitis C antibody–positive); 2. Pregnant or lactating (female participants of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to the start of treatment); 3. Male or female participants of reproductive potential must agree to use appropriate methods of contraception for the duration of study treatment and for at least 30 days after the last dose of protocol treatment; 4. Patients who had CNS involvement that requires radiation; 5. Prior and concomitant therapy; (1) >= 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of standard maintenance therapy (glucocorticoids, vincristine, methotrexate,6-mercaptopurine), tyrosine kinase inhibitors, and steroids). (2) Cytoreduction with prednisone or methylprednisolone for <= 120 hours (5 days) in patients with hyperleukocytosis or extramedullary disease compromising organ function can be initiated and continued for up to 24 hours prior to the start of protocol therapy. (3) At least 21 days must have elapsed since completion of therapy with a biologic agent excluding blinatumomab. For agents that have known adverse events occurring beyond 21 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur. At least 7 days must have elapsed since blinatumomab infusion and patients must have recovered from all toxicities as described above. (4) Intrathecal cytotoxic therapy: No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone. Intrathecal chemotherapy given at the time of diagnostic LP to evaluate for relapse prior to study enrollment is allowed. (5) Anticancer therapy including radiation therapy, other targeted small molecule agents, and investigational agents within 14 days or 5 half-lives, whichever is shorter (Exceptions Ph+ ALL subjects on TKIs at screening may enroll and remain on TKI therapy to control disease); (6) Patients with prior exposure to venetoclax are excluded. (7) Treatment with moderate or strong cytochrome P450 3A (CYP3A) inhibitors within 3 days of starting protocol therapy (see Appendix III for examples); (8) Treatment with moderate or strong CYP3A inducers within 7 days of starting protocol therapy (see Appendix III for examples); (9) Administration or consumption within 3 days prior to the first dose of the study drug of grapefruit or grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit; 6. Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Block 1 response;Block 2 response;Adverse events evaluation;R2PD; | — |
Countries
China
Contacts
Public ContactZhu Xiaofan
Institute of Hematology, Blood Disease Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed