Acute Myeloid Leukemia Myelodisplastic syndrome
Conditions
Interventions
Subjects will receive an active dose SEA-CD70
Sponsors
Seagen Inc
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: SEA-CD70 dose-escalation cohort in relapsed/refractory (HMA-failure) MDS, Part A: 1. Subjects with cytologically/histologically confirmed MDS according to the 2016 World Health Organization (WHO) classification with the following: * Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria as defined either: * 5%-9% blasts in the bone marrow or 2%-4% blasts in the peripheral blood (MDS-EB-1), or * 10%-19% blasts in the bone marrow or 5%-19% blasts in the peripheral blood (MDS-EB-2) * MDS that is relapsed or refractory and must not have other therapeutic options known to provide clinical benefit in MDS available. * Treatment failure after prior HMA therapy for MDS, defined as one of the following: * Progression (per 2006 IWG criteria) at any time after initiation of HMA therapy. * Lack of response (failure to achieve CR, PR, or hematologic improvement [HI] per 2006 IWG criteria) after at least 6 cycles of azacitidine (or equivalent oral HMA) or 4 cycles of decitabine (or equivalent oral HMA). * Relapse after achievement of CR, PR, or HI (per 2006 IWG criteria). * Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to treatment discontinuation). * Subjects with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA. 2. Must be off all treatments for MDS (including HMAs) for >=4 weeks; growth factors (e.g., G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed before and during the study as clinically indicated. 3. Age >=18 years. 4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1 SEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS, Part B: 5. Subjects with cytologically/histologically confirmed MDS according to the 2016 WHO classification with the following: * Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria as defined either: * 5%-9% blasts in the bone marrow or 2%-4% blasts in the peripheral blood (MDS-EB-1), or * 10%-19% blasts in the bone marrow or 5%-19% blasts in the peripheral blood (MDS-EB-2) * MDS that is relapsed or refractory and must not have other therapeutic options known to provide clinical benefit in MDS available. * Treatment failure after prior HMA therapy for MDS defined as one of the following: * Progression (per 2006 IWG criteria) at any time after initiation of HMA therapy. * Lack of response (failure to achieve CR, PR, or HI per 2006 IWG criteria) after at least 6 cycles of azacitidine (or equivalent oral HMA) or 4 cycles of decitabine (or equivalent oral HMA). * Relapse after achievement of CR, PR, or HI (per 2006 IWG criteria). * Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to treatment discontinuation). * Subjects with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA. 6. Must be off all treatments for MDS (including HMAs) for >=4 weeks; growth factors (e.g., G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed before and during the study as clinically indicated. 7. At least one cytopenia (ANC =18 years. 9. ECOG Performance Status of 0-2 SEA-CD70 expansio
Exclusion criteria
Exclusion criteria: 1. History of another malignancy within 3 years before the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS >=90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. 2. Previous exposure to CD70-targeted agents. 3. Prior allogeneic hematopoietic stem cell transplant, for any condition. 4. Central nervous system leukemia based on imaging or documented positive cytology in cerebral spinal fluid. 5. Any uncontrolled Grade 3 or higher (per the National Cancer Institute*s Common Terminology Criteria for Adverse Events [NCI CTCAE], version 5.0) viral, bacterial, or fungal infection within 14 days prior to the first dose of study treatment. Antimicrobial prophylaxis or ongoing treatment of resolving/controlled infection is permitted. 6. Subjects who have experienced major surgery (defined as requiring general anesthesia and hospitalization for >24 hours) or significant traumatic injury that would place the subject at undue risk from study procedures, in the opinion of the investigator, within 14 days before the first dose of study treatment. Subjects must have recovered adequately from the surgery/injury, or complications thereof, prior to starting treatment. 7. Positive for hepatitis B by surface antigen expression. Active hepatitis C infection (positive by PCR or on antiviral therapy for hepatitis C within the last 6 months). Subjects who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks. 8. Known to be positive for human immunodeficiency virus (HIV). 9. Known active or latent tuberculosis. 10. History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura. 11. History of clinically significant chronic liver disease (e.g., liver cirrhosis) and/or ongoing alcohol abuse. 12. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class III-IV (Appendix F) within 6 months prior to their first dose of SEA-CD70. 13. chemotherapy, systemic radiotherapy, biologics, other anti-neoplastic or investigational agents, and/or other antitumor treatment with immunotherapy that is not completed 4 weeks prior to first dose of SEA-CD70. Focal radiotherapy that is not completed 2 weeks prior to the first dose of SEA-CD70. Hydroxyurea or 6-mercaptopurine used for cytoreduction may be given up to 24 hours prior to treatment. 14. Subjects with either of the following: a. A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 2 weeks of first dose of SEA-CD70 (inhaled, topical, intraocular, intranasal, and intraarticular steroids are permitted in the absence of active immune disease, and steroid premedication for prevention of hypersensitivity reactions to radiographic contrast is permitted). b. Active known or suspected clinically significant autoimmune disease or cl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CR rate, CRh rate, ORR, MRD-negative ORR, rate of conversion to TI, and maintenance of TI will be presented with corresponding binomial exact 95% Cis using the All Treated Subjects set. For MDS, binomial exact 95% Cis will also be provided for HI rate and blast clearance rate. For AML, binomial exact 95% Cis will also be provided for CRi rate. DOR, EFS, TTR, and OS will be estimated using the all treated subjects set using Kaplan-Meier methodology, and Kaplan-Meier plots will be provided. Medians will be calculated, where possible. The 95% Cis may also be calculated, as appropriate. Detailed methodology will be provided in the SAP. | — |
Countries
Netherlands
Outcome results
None listed