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

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ClinicalTrials.gov Identifier: NCT04227847
Recruitment Status : Recruiting
First Posted : January 14, 2020
Last Update Posted : December 9, 2020
Sponsor:
Information provided by (Responsible Party):
Seagen Inc.

Tracking Information
First Submitted Date  ICMJE January 10, 2020
First Posted Date  ICMJE January 14, 2020
Last Update Posted Date December 9, 2020
Actual Study Start Date  ICMJE August 7, 2020
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
  • Number of participants with adverse events (AEs) [ Time Frame: 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 ]
  • Number of participants with a dose-limiting toxicity (DLT) at each dose level (Part A only) [ Time Frame: Though end of DLT evaluation period; up to approximately 4 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
  • 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 ]
  • Tmax - Time to maximum concentration attained [ Time Frame: 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 ]
  • Ctrough - Minimum plasma concentration per dosing interval [ Time Frame: 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 ]
  • Incidence of antidrug antibodies (ADA) [ Time Frame: 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
  • Complete remission with incomplete blood count recovery (CRi) rate [ Time Frame: Up to approximately 4 years ]
    Proportion of participants with AML who achieve CRi
  • 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
  • Hematologic response (HI) rate [ Time Frame: Up to approximately 4 years ]
    Proportion of MDS participants with HI
  • Objective 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 or PR.
  • Blast clearance rate for participants with MDS [ Time Frame: Up to approximately 4 years ]
    Proportion of participants with MDS who achieve CR, PR, Marrow CR, or CRh
  • Duration of response (DOR) [ Time Frame: Up to approximately 4 years ]
    For AML, the time from first CR/CRi/CRh response to the first documentation of disease progression, start of new therapy, or death due to any cause. For MDS, the time from first PR/CR to the first documentation of disease progression, start of new therapy, or death due to any cause.
  • 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
  • Event-free survival (EFS) [ Time Frame: Up to approximately 4 years ]
    Time from first dose to the first documentation of progression, disease relapse, or death due to any cause, whichever comes first.
  • MRD-negative ORR [ Time Frame: Up to approximately 4 years ]
    Proporation of participants with AML or MDS who achieve MRD-negative ORR
  • Time to response (TTR) [ Time Frame: Up to approximately 4 years ]
    Time from start of study treatment to the first documentation of objective response
  • 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
  • Maintenance of TI [ Time Frame: Up to approximately 4 years ]
    Number of subjects who were TI at baseline and maintain TI post-baseline
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies
Official Title  ICMJE A Phase 1 Study of SEA-CD70 in Myeloid Malignancies
Brief Summary

This trial will look at a drug called SEA-CD70 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 three 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.

Detailed Description

This is a phase 1, open-label, multicenter, dose-escalation, and cohort expansion study designed to evaluate the safety, tolerability, PK, and antitumor activity of SEA-CD70 in adults with myeloid malignancies. The study will be conducted in up to 3 parts.

Part A is a dose escalation cohort designed to identify the MTD or recommended expansion dose of SEA-CD70 in subjects with relapsed/refractory (HMA-failure) MDS. Part B is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in subjects with relapsed/refractory (HMA-failure) MDS. Part C is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in subjects with relapsed/refractory AML.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Part B and C will enroll in parallel after enrollment of Part A is complete.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myelodyspastic Syndrome
  • Acute Myeloid Leukemia
Intervention  ICMJE Drug: SEA-CD70
Intravenous (IV) infusion on Days 1 and 15 of each treatment cycle
Study Arms  ICMJE
  • Experimental: Part A
    SEA-CD70 dose escalation cohort in relapsed/refractory (HMA-failure) MDS
    Intervention: Drug: SEA-CD70
  • Experimental: Part B
    SEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS
    Intervention: Drug: SEA-CD70
  • Experimental: Part C
    SEA-CD70 expansion cohort in relapsed/refractory AML
    Intervention: Drug: SEA-CD70
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 10, 2020)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2024
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Part A Inclusion Criteria

  • Participants with cytologically/histologically confirmed myelodysplastic syndrome (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 marriw 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 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).
      • Participants with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA.
  • Must be off all treatments for MDS for ≥ 4 weeks; 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% 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 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.
  • At least one cytopenia (absolute neutrophil count [ANC] <1800/μL or platelet count <100,000/μL or hemoglobin [Hgb] <10 g/dL).
  • ECOG Performance Status of 0-2

Part C Inclusion Criteria

  • Participants with relapsed or refractory acute myeloid leukemia (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

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
  • Any uncontrolled Grade 3 or higher 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.
  • Participants who have experienced major surgery (defined as requiring general anesthesia and hospitalization for >24 hours) or significant traumatic injury that would place the participant at undue risk from study procedures, in the opinion of the investigator, within 14 days before the first dose of study treatment.
  • 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). Participants who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks.
  • Known to be positive for human immunodeficiency virus (HIV)
  • Known active or latent tuberculosis
  • History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura
  • History of clinically significant chronic liver disease (e.g. liver cirrhosis) and/or ongoing alcohol abuse
  • 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 within 6 months prior to their first dose of SEA-CD70.
  • 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.
  • Participants with either of the following:

    • 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
    • Active known or suspected clinically significant autoimmune disease or clinically significant autoimmune-related toxicity from prior immuno-oncology-based therapy
  • Known hypersensitivity to any excipient contained in the drug formulation of SEA-CD70
  • Estimated life expectancy <12 weeks
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Seagen Trial Information Support 866-333-7436 clinicaltrials@seagen.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04227847
Other Study ID Numbers  ICMJE SGNS70-101
2019-001917-18 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Seagen Inc.
Study Sponsor  ICMJE Seagen Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Phoenix Ho, MD Seagen Inc.
PRS Account Seagen Inc.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP