A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies

March 29, 2024 updated by: Seagen Inc.

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 patients 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 six groups or "parts."

  • Part A will find out how much SEA-CD70 should be given to patients.
  • Part B will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat patients 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 patients with AML.
  • Part D will find out how much SEA-CD70 with azacitidine should be given to patients.
  • 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 patients with MDS 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 patients with MDS or AML.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 AML arising from MDS, and 2) previously untreated higher-risk (IPSS intermediate-2 or high risk) MDS.
  • 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 (IPSS intermediate-2 or high risk) MDS.
  • 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 AML arising from MDS.

Study Type

Interventional

Enrollment (Estimated)

140

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Netherlands
    • Other
      • Leiden, Other, Netherlands, 2333 ZA
        • Completed
        • Leids Universitair Medisch Centrum ( LUMC)
      • Utrecht, Other, Netherlands, 3584 CX
        • Recruiting
        • University Medical Center (UMC) Utrecht
        • Principal Investigator:
          • Anna van Rhenen, MD
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249
        • Recruiting
        • University of Alabama at Birmingham
        • Principal Investigator:
          • Pankit Vachhani
        • Contact:
          • Caroline Durena
          • Phone Number: 205-934-0306
    • California
      • Duarte, California, United States, 91010-3000
        • Recruiting
        • City of Hope
        • Contact:
        • Principal Investigator:
          • Ahmed M Aribi
      • Los Angeles, California, United States, 90095
        • Recruiting
        • UCLA Department of Medicine - Hematology & Oncology
        • Principal Investigator:
          • Caspian Oliai
        • Contact:
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Colorado Blood Cancer Institute
        • Principal Investigator:
          • Marcello Rotta
        • Contact:
    • Kansas
      • Fairway, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Cancer Center
        • Principal Investigator:
          • Abdulraheem Yacoub
        • Contact:
    • Kentucky
      • Louisville, Kentucky, United States, 40207
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Principal Investigator:
          • Amir Fathi
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
        • Principal Investigator:
          • Jessica Liegel
        • Contact:
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Institute / Wayne State University
        • Principal Investigator:
          • Jay Yang
        • Contact:
    • New Mexico
      • Farmington, New Mexico, United States, 87401
        • Recruiting
        • San Juan Oncology Associates
        • Principal Investigator:
          • Sardar Z Imam
        • Contact:
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center
        • Principal Investigator:
          • Joseph Jurcic
        • Contact:
          • Caroline Dicker
          • Phone Number: 212-305-2696
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • University Hospitals Cleveland Medical Center
        • Contact:
        • Principal Investigator:
          • Benjamin K Tomlinson
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic, The
        • Principal Investigator:
          • Anjali Advani
        • Contact:
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • James Cancer Hospital / Ohio State University
        • Principal Investigator:
          • Nicole Grieselhuber
        • Contact:
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina/Hollings Cancer Center
        • Contact:
        • Principal Investigator:
          • Praneeth Baratam
      • Greenville, South Carolina, United States, 29607
        • Recruiting
        • Saint Francis Hospital / Bon Secours - South Carolina
        • Contact:
          • Sharon (Nikki) N Thompson
          • Phone Number: 864-603-6238
        • Principal Investigator:
          • Sharif S Khan
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Completed
        • Tennessee Oncology-Nashville/Sarah Cannon Research Institute
    • Texas
      • Dallas, Texas, United States, 75246
        • Recruiting
        • Texas Oncology - Fort Worth
        • Contact:
        • Principal Investigator:
          • Edward J Pearson
      • Houston, Texas, United States, 77030-4095
        • Completed
        • MD Anderson Cancer Center / University of Texas
      • Houston, Texas, United States, 77007
        • Recruiting
        • Houston Methodist Cancer Center
        • Principal Investigator:
          • Shilpan S. Shah, MD
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Swedish Cancer Institute
        • Contact:
        • Principal Investigator:
          • Daniel Egan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Part A Inclusion Criteria

  • Participants 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 criteria as defined either:

      • 5%-9% blasts in the bone marrow or 2%-4% blasts in the peripheral blood or
      • 10%-19% blasts in the bone marrow or 5%-19% blasts in the peripheral blood
    • 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 hypomethylating agent (HMA) therapy for MDS, defined as one of the following:

      • Progression (per 2006 International Working Group [IWG] criteria) at any time after initiation of HMA therapy.
      • Lack of response (failure to achieve complete remission [CR], partial response [PR], or hematologic improvement [HI] per 2006 IWG criteria) after at least 6 cycles of azacitidine (or equivalent HMA) or 4 cycles of decitabine (or equivalent 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).
      • Participants with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA.
  • Must be off HMA therapy ≥ 2 weeks and must be off any other treatments for MDS for ≥ 4 weeks prior to first dose of SEA-CD70; growth factors and transfusions are allowed before and during the study as clinically indicated
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Part B Inclusion Criteria

  • Participants with cytologically/histologically confirmed MDS according to the 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, or
      • 10%-19% blasts in the bone marrow or 5%-19% blasts in the peripheral blood
    • 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 4 cycles of decitabine.
      • 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).
      • Participants with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA.
  • Must be off HMA therapy ≥ 2 weeks and must be off any other systemic treatments for MDS for ≥ 4 weeks prior to first dose of SEA-CD70; growth factors and transfusions are allowed before and during the study as clinically indicated.
  • ECOG Performance Status of 0-2

Part C Inclusion Criteria

  • Participants with relapsed or refractory AML according to the WHO 2016 classification (except for acute promyelocytic leukemia [APL]):

    • Who have received either 2 or 3 previous regimens to treat active disease. Post-remission treatments, intrathecal chemotherapy, and radiotherapy are not considered 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 (defined as failure to achieve CR after 1-2 courses of induction therapy)
      • First CR duration <6 months
      • Adverse-risk per European Leukemia Net (ELN) genetic risk stratification
      • Secondary AML (prior history of MDS or therapy-related)
  • Age 18-75 years
  • ECOG performance status of 0-2

Parts D and F Inclusion Criteria

  • Participants with one of the following confirmed diagnoses:

    • MDS with excess blasts (MDS-EB), defined as 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)
    • AML with ≤ (less than or equal to) 30% blasts in the peripheral blood or bone marrow, with known history of MDS
  • 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
  • Must be off any other systemic treatment for AML/MDS. Must be off HMA therapy ≥ (greater than or equal to) 2 weeks and any other systemic treatments for MDS for ≥ (greater than or equal to) 4 weeks prior to first dose of SEA-CD70
  • ECOG Performance Status 0-2

Parts D and E Inclusion Criteria

  • Participants with previously untreated, cytologically/histologically confirmed MDS according to 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)
  • Participants with higher-risk MDS per International Prognostic Scoring System (IPSS)
  • ECOG Performance Status 0-2

Exclusion Criteria (All Parts)

  • 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.
  • Previous exposure to CD70-targeted agents
  • Prior allogeneic hematopoietic stem cell transplant, for any condition
  • Central nervous system leukemia based on imaging or documented positive cytology in cerebral spinal fluid
  • History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura
  • Parts D and F only: Prior oral HMA or oral HMA-combinations

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 AML arising from MDS, and previously untreated higher-risk MDS
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
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 AML arising from MDS
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events (AEs)
Time Frame: 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.
Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Number of participants with laboratory abnormalities
Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
To be summarized using descriptive statistics.
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)
Time Frame: Though end of DLT evaluation period; up to approximately 4 weeks
To be summarized using descriptive statistics.
Though end of DLT evaluation period; up to approximately 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AUC - Area under the plasma concentration-time curve
Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
To be summarized using descriptive statistics.
Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Tmax - Time to maximum concentration attained
Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
To be summarized using descriptive statistics.
Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Cmax - Maximum observed plasma concentration
Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
To be summarized using descriptive statistics.
Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Ctrough - Minimum plasma concentration per dosing interval
Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
To be summarized using descriptive statistics.
Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
T1/2 - Terminal elimination half-life
Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
To be summarized using descriptive statistics.
Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Incidence of antidrug antibodies (ADA)
Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
To be summarized using descriptive statistics.
Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Complete remission (CR) Rate
Time Frame: Up to approximately 4 years
Proportion of participants with AML or MDS who achieve CR
Up to approximately 4 years
Complete remission with incomplete blood count recovery (CRi) rate
Time Frame: Up to approximately 4 years
Proportion of participants with AML who achieve CRi
Up to approximately 4 years
Complete remission with partial hematologic recovery (CRh) rate
Time Frame: Up to approximately 4 years
Proportion of participants with AML or MDS who achieve CRh
Up to approximately 4 years
Hematologic response (HI) rate
Time Frame: Up to approximately 4 years
Proportion of MDS participants with HI
Up to approximately 4 years
Overall response rate (ORR)
Time Frame: 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, CRh, or PR.
Up to approximately 4 years
Blast clearance rate for participants with MDS
Time Frame: Up to approximately 4 years
Proportion of participants with MDS who achieve a best response of CR, CRh, or Marrow CR
Up to approximately 4 years
Duration of remission (DOR)
Time Frame: Up to approximately 4 years
For AML, the time from first CR, CRi, CRh, or PR to the first documentation of disease progression or death due to any cause. For MDS, the time from first documentation of PR, CR, or CRh to the first documentation of disease progression or death due to any cause.
Up to approximately 4 years
Overall survival (OS)
Time Frame: Up to approximately 4 years
Time from start of study treatment to the date of death due to any cause
Up to approximately 4 years
Event-free survival (EFS)
Time Frame: Up to approximately 4 years
Time from first dose to the first documentation of progression, failure to achieve remission within the first 6 cycles, disease relapse, or death due to any cause, whichever comes first.
Up to approximately 4 years
MRD-negative ORR
Time Frame: Up to approximately 4 years
Proportion of participants with AML or MDS who achieve objective response and MRD-negative status
Up to approximately 4 years
Time to response (TTR)
Time Frame: Up to approximately 4 years
Time from start of study treatment to the first documentation of objective response
Up to approximately 4 years
Rate of conversion to transfusion independence (TI)
Time Frame: Up to approximately 4 years
Proportion of participants who convert from transfusion dependence at baseline to TI post-baseline
Up to approximately 4 years
Rate of TI maintenance
Time Frame: Up to approximately 4 years
Proportion of participants who were TI at baseline and maintain TI post-baseline
Up to approximately 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seagen Inc.

Investigators

  • Study Director: Juan Pinelli, PA-C, MMSc, Seagen Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 7, 2020

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

November 30, 2026

Study Registration Dates

First Submitted

January 10, 2020

First Submitted That Met QC Criteria

January 10, 2020

First Posted (Actual)

January 14, 2020

Study Record Updates

Last Update Posted (Actual)

April 2, 2024

Last Update Submitted That Met QC Criteria

March 29, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SGNS70-101
  • 2019-001917-18 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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