Myelodysplastic SyndromePhase 1NCT04227847
A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies
A Phase 1 study testing SEA-CD70, azacitidine and Venetoclax in people with Myelodysplastic Syndrome and Acute Myeloid Leukemia, run by Seagen, a wholly owned subsidiary of Pfizer at 52 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- What is being tested?
- SEA-CD70, azacitidine and Venetoclax
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 52 sitesin 3 countries
- Study dates
- 7 Aug 2020to 3 Jul 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Trial locations and contacts
52 sites in 3 countries.
52 sites in 3 countries
United States47 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Dept. of Medicine, UAB ONeal Comprehensive Cancer Center
Birmingham, Alabama, 35294
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber/Mass General Brigham Cancer Care, Inc
Boston, Massachusetts, 02215
Hollings Cancer Center
Charleston, South Carolina, 29425
Medical University of South Carolina- Ashley River Tower
Charleston, South Carolina, 29425
Medical University of South Carolina- Investigational Drug Services
Charleston, South Carolina, 29425
Medical University of South Carolina- University Hospital
Charleston, South Carolina, 29425
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
The Ohio State University Wexner Medical Center/James Cancer Hospital
Columbus, Ohio, 43210
Baylor Research Institute
Dallas, Texas, 75204
Baylor University Medical Center, Investigational Drug Services, Department of Pharmacy
Dallas, Texas, 75246
Baylor University Medical Center
Dallas, Texas, 75246
Colorado Blood Cancer Institute, Lab
Denver, Colorado, 80218
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Presbyterian/St. Luke's Medical Center
Denver, Colorado, 80218
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010
IP Address: City of Hope Investigational Drug Services(IDS)
Duarte, California, 91010
The University of Kansas Cancer Center ,Investigational Drug Services
Fairway, Kansas, 66205
The University of Kansas Clinical Research Center
Fairway, Kansas, 66205
Karmanos Cancer Institute Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
The University of Kansas Hospital
Kansas City, Kansas, 66160
University of Kansas Hospital Cambridge North Tower A
Kansas City, Kansas, 66160
University of Kansas Medical center Medical office building
Kansas City, Kansas, 66160
University of Kansas Medical Center Research Institute
Kansas City, Kansas, 66160
The University of Kansas Cancer Center - Medical Oncology Clinic
Kansas City, Missouri, 64116
The University of Kansas Cancer Center -North
Kansas City, Missouri, 64154
The University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
UCLA Hematology-Oncology Clinic
Los Angeles, California, 90095
Norton Hospitals, Inc
Louisville, Kentucky, 40202
Norton Cancer Institute, St. Matthews Campus, Attn. Becky Champion, PharmD
Louisville, Kentucky, 40207
Norton Cancer Institute, St. Matthews Campus
Louisville, Kentucky, 40207
Norton Women & Children's Hospital
Louisville, Kentucky, 40207
Columbia University Irving Medical Center
New York, New York, 10032
CUIMC Research Pharmacy
New York, New York, 10032
The New York and Presbyterian Hospital
New York, New York, 10032
The University of Kansas Cancer Center - Overland Park
Overland Park, Kansas, 66210
The University of Kansas Cancer Center - Indian Creek Campus
Overland Park, Kansas, 66211
Swedish Cancer Institute
Seattle, Washington, 98104
Swedish Medical Center
Seattle, Washington, 98122
The University of Kansas Cancer Center
Westwood, Kansas, 66205
Japan3 sites
Nippon Medical School Hospital
Bunkyo-ku, Tokyo, 113-8603
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Yamagata University Hospital
Yamagata, 990-9585
Netherlands2 sites
Pharmacy - UMC Utrecht t.a.v. Apotheek KGO
Utrecht, 3584 CW
University Medical Center (UMC) Utrecht
Utrecht, 3584 CX
About this study
Official title: A Phase 1 Study of SEA-CD70 in Myeloid Malignancies
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 compared to azacitidine alone 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.
Read the 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 vs 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
- Conditions
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- Being tested
- SEA-CD70, azacitidine, Venetoclax
- Keywords
- Seattle Genetics
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SEA-CD70Drug
Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
azacitidineDrug
Also called VIDAZA
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.
VenetoclaxDrug
Also called Venclexta
400 mg /day PO, continuously; administered with ramping
| Study group | Role | What they receive |
|---|---|---|
| Part A | Experimental | SEA-CD70 dose escalation cohort in relapsed/refractory (HMA-failure) MDS Receives: Drug: SEA-CD70 |
| Part B | Experimental | SEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS Receives: Drug: SEA-CD70 |
| Part C | Experimental | SEA-CD70 expansion cohort in relapsed/refractory AML Receives: Drug: SEA-CD70 |
| Part D | Experimental | SEA-CD70 + azacitidine dose-finding/dose optimization cohorts in relapsed/refractory MDS or MDS/AML, and previously untreated higher-risk MDS or MDS/AML Receives: Drug: SEA-CD70; Drug: azacitidine |
| Part E | Experimental | SEA-CD70 + azacitidine vs azacitidine expansion cohort in previously untreated higher-risk MDS or MDS/AML Receives: Drug: SEA-CD70; Drug: azacitidine |
| Part F | Experimental | SEA-CD70 + azacitidine expansion cohort in relapsed/refractory MDS or MDS/AML Receives: Drug: SEA-CD70; Drug: azacitidine |
| Part G | Experimental | SEA-CD70 + azacitidine +venetoclax dose-finding/dose optimization in previously untreated and unfit for induction therapy AML Receives: Drug: SEA-CD70; Drug: azacitidine; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events (AEs)
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.
Measured: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Number of participants with laboratory abnormalities
To be summarized using descriptive statistics.
Measured: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Number of participants with a dose-limiting toxicity (DLT) at each dose level (Parts A and D only)
To be summarized using descriptive statistics.
Measured: Though end of DLT evaluation period; up to approximately 4 weeks
Secondary outcomes (20)
AUC - Area under the plasma concentration-time curve
To be summarized using descriptive statistics.
Measured: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Tmax - Time to maximum concentration attained
To be summarized using descriptive statistics.
Measured: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Cmax - Maximum observed plasma concentration
To be summarized using descriptive statistics.
Measured: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Ctrough - Minimum plasma concentration per dosing interval
To be summarized using descriptive statistics.
Measured: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
T1/2 - Terminal elimination half-life
To be summarized using descriptive statistics.
Measured: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Incidence of antidrug antibodies (ADA)
To be summarized using descriptive statistics.
Measured: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Complete remission (CR) Rate and complete remission equivalent (CReq) rate
Proportion of participants with AML, MDS/AML or MDS who achieve CR or CReq
Measured: Up to approximately 4 years
Complete remission with incomplete blood count recovery (CRi) rate
Proportion of participants with AML who achieve CRi
Measured: Up to approximately 4 years
Complete remission with limited count recovery (CRL) rate for participants with MDS or MDS/AML
Proportion of participants with MDS or MDS/AML who achieve CRL
Measured: Up to approximately 4 years
Complete remission with partial hematologic recovery (CRh) rate
Proportion of participants with AML, MDS/AML, or MDS who achieve CRh
Measured: Up to approximately 4 years
Hematologic response (HI) rate
Proportion of participants with MDS or MDS/AML with HI
Measured: Up to approximately 4 years
Overall response rate (ORR)
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
Measured: Up to approximately 4 years
Duration of remission (DOR)
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
Measured: Up to approximately 4 years
Overall survival (OS)
Time from start of study treatment to the date of death due to any cause
Measured: Up to approximately 4 years
Event-free survival (EFS)
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.
Measured: Up to approximately 4 years
Progression-free survival (PFS)
Time from first dose to the first documentation of progression, disease relapse, or death from any cause, whichever comes first
Measured: Up to approximately 4 years
MRD-negative ORR
Proportion of participants with AML or MDS who achieve MRD-negative ORR
Measured: Up to approximately 4 years
Time to response (TTR)
Time from start of study treatment to the first documentation of objective response
Measured: Up to approximately 4 years
Rate of conversion to transfusion independence (TI)
Proportion of participants who convert from transfusion dependence at baseline to TI post-baseline
Measured: Up to approximately 4 years
Rate of TI maintenance
Proportion of participants who were TI at baseline and maintain TI post-baseline
Measured: Up to approximately 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2020
- Study start7 Aug 2020
- Primary completion4 Jul 2027 (estimated)
- Study completion3 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by Seagen, a wholly owned subsidiary of PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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.
- Masking
- None (open label)
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seagen, a wholly owned subsidiary of Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04227847
- Sponsor's protocol ID
- SGNS70-101
- Other IDs
- C5781001, 2023-506945-42-00, 2023
- Status last verified
- Sep 2026
- First submitted
- 10 Jan 2020
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Dewulf J, Flieswasser T, Delahaye T, Vangestel C, Miranda A, de Haard H, Jacobs J, Smits E, Van den Wyngaert T, Elvas F. Site-specific 68Ga-labeled nanobody for PET imaging of CD70 expression in preclinical tumor models. EJNMMI Radiopharm Chem. 2023 Apr 24;8(1):8. doi: 10.1186/s41181-023-00194-3.
PubMed 37093350