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Purpose

This trial will look at a drug called SEA-CD70 with and without azacitidine, to find out if it is safe for participants with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It will study SEA-CD70 to find out what its side effects are and if it works for AML and MDS. A side effect is anything the drug does besides treating cancer. This study will have seven groups or "parts." - Part A will find out how much SEA-CD70 should be given to participants - Part B will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat participants with MDS. - Part C will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat participants with AML. - Part D will find out how much SEA-CD70 with azacitidine should be given to participants - Part E will use the dose found in Part D to find out how safe SEA-CD70 with azacitidine is and if it works to treat participants with MDS or MDS/AML that has not been treated. - Part F will use the dose found in Part D to find out how safe SEA-CD70 with azacitidine is and if it works to treat participants with MDS or MDS/AML. - Part G will find out how much SEA-CD70 with azacitidine and with venetoclax should be given to participants with AML. Also, to evaluate safety and tolerability of PF-08046040 in combination with azacitidine and venetoclax in participants with previously untreated AML who are unfit for standard induction chemotherapy.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Participants with cytologically/histologically confirmed MDS (2016 World Health Organization (WHO) classification) with - Measurable disease per WHO MDS with excess blasts criteria - MDS that is relapsed or refractory and must not have other therapeutic options - Treatment failure after prior hypomethylating agent (HMA) therapy for MDS - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Part B Inclusion Criteria - Participants with cytologically/histologically confirmed MDS (WHO classification) with: - Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria - MDS that is relapsed or refractory and must not have other therapeutic options - Treatment failure after prior HMA therapy for MDS - ECOG Performance Status of 0-2 Part C Inclusion Criteria - Participants with relapsed or refractory AML (ICC 2022) (except for acute promyelocytic leukemia [APL]): - Who have received either 2 or 3 previous regimens - Who have received 1 previous regimen to treat active disease and have at least one of the following: - Age > 60 and ≤75 years. - Primary resistant AML or secondary AML - First CR duration <6 months - Adverse-risk per European Leukemia Network genetic risk stratification - Age 18-75 years - ECOG performance status of 0-2 Parts D and F Inclusion Criteria - Participants with diagnosis of MDS or MDS/AML (ICC 2022 criteria) - Disease which has relapsed, failed to respond after minimum of 6 cycles, or progressed following an HMA in the immediately preceding line of therapy. - Eligible for continued therapy with azacitidine - ECOG Performance Status 0-2 Parts D and E Inclusion Criteria - Participants with diagnosis of MDS or MDS/AML (ICC 2022 criteria), previously untreated. - Participants with higher-risk per IPSS-M MDS and MDS/AML - ECOG Performance Status 0-2 Part G Inclusion Criteria - Participants with diagnosis of AML (ICC 2022 criteria), previously untreated and ineligible for standard induction chemotherapy. - Age ≥18 years. - ECOG Performance Status of 0-2.

Exclusion Criteria

(All Parts) - Previous exposure to CD70-targeted agents - Prior allogeneic hematopoietic stem cell transplant, for any condition - Central nervous system leukemia - History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura - Parts D, F and G only: Prior oral HMA or oral HMA-combinations - Part G: conditions that preclude enteral route of administration; concomitant use of strong/moderate CYP3A inducers; history of myeloproliferative neoplasm

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Parts B and C may enroll in parallel after enrollment of Part A is complete. Part D will enroll after Part A is complete. Parts E, F and Part G will enroll in parallel once Part D is complete.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part A 		SEA-CD70 dose escalation cohort in relapsed/refractory (HMA-failure) MDS
  • Drug: SEA-CD70
    Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
Experimental
Part B 		SEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS
  • Drug: SEA-CD70
    Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
Experimental
Part C 		SEA-CD70 expansion cohort in relapsed/refractory AML
  • Drug: SEA-CD70
    Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
Experimental
Part D 		SEA-CD70 + azacitidine dose-finding/dose optimization cohorts in relapsed/refractory MDS or MDS/AML, and previously untreated higher-risk MDS or MDS/AML
  • Drug: SEA-CD70
    Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
  • Drug: azacitidine
    75mg/m^2 injected under the skin (SC; subcutaneous) or given into the vein (IV; intravenously) on Days 1 through 7 of each treatment cycle.
    Other names:
    • VIDAZA
Experimental
Part E 		SEA-CD70 + azacitidine expansion cohort in previously untreated higher-risk MDS or MDS/AML
  • Drug: SEA-CD70
    Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
  • Drug: azacitidine
    75mg/m^2 injected under the skin (SC; subcutaneous) or given into the vein (IV; intravenously) on Days 1 through 7 of each treatment cycle.
    Other names:
    • VIDAZA
Experimental
Part F 		SEA-CD70 + azacitidine expansion cohort in relapsed/refractory MDS or MDS/AML
  • Drug: SEA-CD70
    Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
  • Drug: azacitidine
    75mg/m^2 injected under the skin (SC; subcutaneous) or given into the vein (IV; intravenously) on Days 1 through 7 of each treatment cycle.
    Other names:
    • VIDAZA
Experimental
Part G 		SEA-CD70 + azacitidine +venetoclax dose-finding/dose optimization in previously untreated and unfit for induction therapy AML
  • Drug: SEA-CD70
    Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
  • Drug: azacitidine
    75mg/m^2 injected under the skin (SC; subcutaneous) or given into the vein (IV; intravenously) on Days 1 through 7 of each treatment cycle.
    Other names:
    • VIDAZA
  • Drug: Venetoclax
    400 mg /day PO, continuously; administered with ramping
    Other names:
    • Venclexta

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
Seagen, a wholly owned subsidiary of Pfizer

Study Contact

Seagen Pfizer CT.gov Call Center
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com

Detailed Description

This is a phase 1, open-label, multicenter, dose-finding, and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SEA-CD70 monotherapy and SEA-CD70 in combination with azacitidine in adults with myeloid malignancies. The study will be conducted in up to 6 parts. - Part A is a dose-escalation cohort designed to identify the MTD or recommended expansion dose of SEA-CD70 monotherapy in participants with relapsed/refractory (hypomethylating agent [HMA]-failure) MDS. - Part B is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 monotherapy in participants with relapsed/refractory (HMA-failure) MDS. - Part C is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 monotherapy in participants with relapsed/refractory AML. - Part D contains dose-finding/dose optimization cohorts designed to evaluate the safety/tolerability and identify the recommended expansion dose of SEA-CD70 in combination with azacitidine in participants with 1) relapsed/refractory (HMA-failure) MDS or MDS/AML, and 2) previously untreated higher-risk per IPSS-M (Moderate High, High or Very High) MDS or MDS/AML. - Part E is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in combination with azacitidine in participants with previously untreated higher-risk per IPSS-M (Moderate High, High, or Very High) MDS or MDS/AML. - Part F is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in combination with azacitidine in participants with relapsed/refractory (HMA-failure) MDS or MDS/AML. - Part G will find out how much SEA-CD70 with azacitidine and with venetoclax should be given to participants with previously untreated AML who are unfit for standard of care induction chemotherapy

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.