A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies
- Conditions
- Myelodysplastic SyndromeAcute Myeloid Leukemia
- Interventions
- Registration Number
- NCT04227847
- Lead Sponsor
- Seagen, a wholly owned subsidiary of Pfizer
- Brief Summary
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.
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 178
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A SEA-CD70 SEA-CD70 dose escalation cohort in relapsed/refractory (HMA-failure) MDS Part B SEA-CD70 SEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS Part C SEA-CD70 SEA-CD70 expansion cohort in relapsed/refractory AML Part D SEA-CD70 SEA-CD70 + azacitidine dose-finding/dose optimization cohorts in relapsed/refractory MDS or MDS/AML, and previously untreated higher-risk MDS or MDS/AML Part D azacitidine SEA-CD70 + azacitidine dose-finding/dose optimization cohorts in relapsed/refractory MDS or MDS/AML, and previously untreated higher-risk MDS or MDS/AML Part E SEA-CD70 SEA-CD70 + azacitidine expansion cohort in previously untreated higher-risk MDS or MDS/AML Part E azacitidine SEA-CD70 + azacitidine expansion cohort in previously untreated higher-risk MDS or MDS/AML Part F SEA-CD70 SEA-CD70 + azacitidine expansion cohort in relapsed/refractory MDS or MDS/AML Part F azacitidine SEA-CD70 + azacitidine expansion cohort in relapsed/refractory MDS or MDS/AML Part G SEA-CD70 SEA-CD70 + azacitidine +venetoclax dose-finding/dose optimization in previously untreated and unfit for induction therapy AML Part G azacitidine SEA-CD70 + azacitidine +venetoclax dose-finding/dose optimization in previously untreated and unfit for induction therapy AML Part G Venetoclax SEA-CD70 + azacitidine +venetoclax dose-finding/dose optimization in previously untreated and unfit for induction therapy AML
- Primary Outcome Measures
Name Time Method Number of participants with adverse events (AEs) Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Number of participants with laboratory abnormalities Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years To be summarized using descriptive statistics.
Number of participants with a dose-limiting toxicity (DLT) at each dose level (Parts A and D only) Though end of DLT evaluation period; up to approximately 4 weeks To be summarized using descriptive statistics.
- Secondary Outcome Measures
Name Time Method Rate of TI maintenance Up to approximately 4 years Proportion of participants who were TI at baseline and maintain TI post-baseline
Complete remission with partial hematologic recovery (CRh) rate Up to approximately 4 years Proportion of participants with AML, MDS/AML, or MDS who achieve CRh
Overall response rate (ORR) Up to approximately 4 years For AML, the proportion of participants who achieve a best response of CR, CRi, CRh, or partial response (PR). For MDS, the proportion of participants who achieve a best response of CR, CReq, CRL, CRh, PR, or HI
AUC - Area under the plasma concentration-time curve Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years To be summarized using descriptive statistics.
Cmax - Maximum observed plasma concentration Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years To be summarized using descriptive statistics.
Incidence of antidrug antibodies (ADA) Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years To be summarized using descriptive statistics.
Complete remission with limited count recovery (CRL) rate for participants with MDS or MDS/AML Up to approximately 4 years Proportion of participants with MDS or MDS/AML who achieve CRL
Tmax - Time to maximum concentration attained Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years To be summarized using descriptive statistics.
Ctrough - Minimum plasma concentration per dosing interval Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years To be summarized using descriptive statistics.
Hematologic response (HI) rate Up to approximately 4 years Proportion of participants with MDS or MDS/AML with HI
Overall survival (OS) Up to approximately 4 years Time from start of study treatment to the date of death due to any cause
Event-free survival (EFS) Up to approximately 4 years Time from first dose to the first documentation of progression, failure to achieve remission within 6 months of study entry, disease relapse, or death due to any cause, whichever comes first.
T1/2 - Terminal elimination half-life Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years To be summarized using descriptive statistics.
Complete remission (CR) Rate and complete remission equivalent (CReq) rate Up to approximately 4 years Proportion of participants with AML, MDS/AML or MDS who achieve CR or CReq
Complete remission with incomplete blood count recovery (CRi) rate Up to approximately 4 years Proportion of participants with AML who achieve CRi
Duration of remission (DOR) Up to approximately 4 years For AML, the time from first CR/CRi/CRh/PR response to the first documentation of disease progression, start of new anticancer therapy, or death due to any cause. For MDS, the time from first CR (or Req)/CRL/CRh/PR to the first documentation of disease progression, start of new anticancer therapy, or death due to any cause
Time to response (TTR) Up to approximately 4 years Time from start of study treatment to the first documentation of objective response
Progression-free survival (PFS) Up to approximately 4 years Time from first dose to the first documentation of progression, disease relapse, or death from any cause, whichever comes first
MRD-negative ORR Up to approximately 4 years Proportion of participants with AML or MDS who achieve MRD-negative ORR
Rate of conversion to transfusion independence (TI) Up to approximately 4 years Proportion of participants who convert from transfusion dependence at baseline to TI post-baseline
Trial Locations
- Locations (49)
ONeal Comprehensive Cancer Center at UAB
🇺🇸Birmingham, Alabama, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
🇺🇸Duarte, California, United States
IP Address: City of Hope Investigational Drug Services(IDS)
🇺🇸Duarte, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
UCLA Hematology-Oncology Clinic
🇺🇸Los Angeles, California, United States
Colorado Blood Cancer Institute, Lab
🇺🇸Denver, Colorado, United States
Presbyterian/St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
The University of Kansas Cancer Center ,Investigational Drug Services
🇺🇸Fairway, Kansas, United States
The University of Kansas Clinical Research Center
🇺🇸Fairway, Kansas, United States
The University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
University of Kansas Hospital Cambridge North Tower A
🇺🇸Kansas City, Kansas, United States
University of Kansas Medical center Medical office building
🇺🇸Kansas City, Kansas, United States
The University of Kansas Cancer Center - Overland Park
🇺🇸Overland Park, Kansas, United States
The University of Kansas Cancer Center - Indian Creek Campus
🇺🇸Overland Park, Kansas, United States
Norton Cancer Institute, St. Matthews Campus, Attn. Becky Champion, PharmD
🇺🇸Louisville, Kentucky, United States
Norton Cancer Institute, St. Matthews Campus
🇺🇸Louisville, Kentucky, United States
Norton Women & Children's Hospital
🇺🇸Louisville, Kentucky, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Karmanos Cancer Institute Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
The University of Kansas Cancer Center - Medical Oncology Clinic
🇺🇸Kansas City, Missouri, United States
The University of Kansas Cancer Center - Radiation Oncology Clinic
🇺🇸Kansas City, Missouri, United States
The University of Kansas Cancer Center - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
The University of Kansas Cancer Center -North
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina- Investigational Drug Services
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina- University Hospital
🇺🇸Charleston, South Carolina, United States
St. Francis Hospital
🇺🇸Greenville, South Carolina, United States
St. Francis Cancer Center
🇺🇸Greenville, South Carolina, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
CUIMC Research Pharmacy
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
The Ohio State University Wexner Medical Center/James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina- Ashley River Tower
🇺🇸Charleston, South Carolina, United States
Baylor University Medical Center, Investigational Drug Services, Department of Pharmacy
🇺🇸Dallas, Texas, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Pharmacy - UMC Utrecht t.a.v. Apotheek KGO
🇳🇱Utrecht, Netherlands
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
UCLA Department of Medicine - Hematology & Oncology
🇺🇸Los Angeles, California, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
James Cancer Hospital / Ohio State University
🇺🇸Columbus, Ohio, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
University Medical Center (UMC) Utrecht
🇳🇱Utrecht, Netherlands