Relapsed or refractory CD22-positive ALL Relapsed or refractory CD22-positive lymphoblastic lymphoma and bone marrow involvement
Conditions
Interventions
For the dose level 1 (starting dose), pediatric patients with ALL will be treated with 1.8 mg/m2 inotuzumab ozogamicin per cycle with a fractionated dose regimen. Patients will receive 0.8 mg/m2 on Da
Sponsors
National Cancer Center Hospital Nagoya Medical Center Osaka City General Hospital Kyushu Cancer Center Hyogo Prefectural Kobe Children's Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Relapsed or refractory CD22-positive ALL (>=5% marrow blasts, assessed by morphology), or relapsed or refractory CD22-positive lymphoblastic lymphoma and bone marrow involvement >=5% lymphoblasts by morphologic assessment. 2. Ph+ ALL patients must have failed treatment with at least 1 second or third generation tyrosine kinase inhibitor and standard multi-agent induction chemotherapy; 3. Patients with late relapse should be deemed poor candidates for reinduction with initial therapy; 4. Patients from 1 to 17 years old at the timing of informed consent. 5. Karnofsky performance status 60% to 100% for patients >=17 years of age and Lansky performance status 60% to 100% for patients <=16 years of age 6. Adequate liver function, including total serum bilirubin <=1.5 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) <=2.5 x ULN. If organ function abnormalities are considered due to tumor, total serum bilirubin must be <=2 x ULN and AST/ALT <=2.5 x ULN. Pediatric reference ranges will be used. 7. Serum creatinine <=1.5 x upper limit of normal (ULN) (pediatric reference ranges will be used) or estimated creatininee clearance of >=40 mL/min by standard calculation method of site. 8. Pregnant, lactating, childbearing potential female or childbearing potential male must agree to use a highly effective method of contraception throughout the study and for a minimum of 90 days after the last dose of treatment. 9. Evidence that an informed consent document personally signed and dated by the patient or the legal representative such as parents indicates that the patient has been informed of all pertinent aspects of the study before any study specific activity is performed; 10. Patients who are able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 11. Asian patient.
Exclusion criteria
Exclusion criteria: 1. Isolated extramedullary relapse (testicular or CNS) 2. Burkitt's or mixed phenotype acute leukemia (WHO 2008 criteria) 3. Active central nervous system leukemia. Prophylactic intrathecal medication is not excluded. 4. Having undergone prior chemotherapy at enrollment excluding therapy to reduce the circulating lymphoblast count or palliation: steroids, hydroxycarbamide, or vincristine 5. Prior administration of monoclonal antibodies within 4 weeks of enrollment 6. Prior rituximab treatment at enrollment 7. Prior allogeneic HSCT or other anti-CD22 immunotherapy <=4 months before enrollment 8. Having completed immunosuppression therapy in GvHD prior to enrollment. With >= Grade 2 acute GvHD, or extensive chronic GvHD at enrollment 9. Systemic vasculitides, or primary or secondary immunodeficiency 10. Active HbsAg B or HCV C infection or seropositivity for HIV 11. Major surgery within <=4 weeks before enrollment 12. Unstable or severe uncontrolled medical condition 13. Concurrent active malignancy excluding non-melanoma skin cancer that has been definitely treated with radiation or surgery, calculated cervical high grade squamous intraepithelial lesion (CIN2, CIN3), or localized prostate cancer. Those with previous malignancies in disease free for >=2 years 14. <45% cardiac function (left ventricular ejection fraction), or class >=3 (Modified Ross Heart Failure Classification) 15. Active heart disease 16. Myocardial infarction <=6 months before enrollment 17. History of chronic liver disease 18. History of hepatic veno-occlusive disease or sinusoidal obstruction syndrome 19. Live vaccine administration <=6 weeks before enrollment 20. Evidence of serious active infection 21. History of severe allergic or anaphylactic reaction to any humanized monoclonal antibodies 22. Participation in other studies 23. History of Inotuzumab ozogamicin administration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of first cycle dose limiting toxicities (DLTs) of inotuzumab ozogamicin | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) PK profile of inotuzumab ozogamicin 2) Safety profile, including VOD/SOS 3) Complete remission rate (CR/CRi ) 4) Minimal residual disease (MRD) status in patients achieving a CR/CRi 5) Overall survival (OS) | — |
Countries
Japan
Contacts
Public ContactYutaka Ito
National Hospital Organization Nagoya Medical Center Department of Clinical Research Planning and Management, Clinical Research Center
Outcome results
None listed