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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04227847
Recruitment Status : Recruiting
First Posted : January 14, 2020
Last Update Posted : May 10, 2022
Sponsor:
Information provided by (Responsible Party):
Seagen Inc.

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.


Condition or disease Intervention/treatment Phase
Myelodyspastic Syndrome Acute Myeloid Leukemia Drug: SEA-CD70 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
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
Official Title: A Phase 1 Study of SEA-CD70 in Myeloid Malignancies
Actual Study Start Date : August 7, 2020
Estimated Primary Completion Date : November 30, 2022
Estimated Study Completion Date : October 31, 2024


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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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 ]
    To be summarized using descriptive statistics.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Complete remission (CR) Rate [ Time Frame: Up to approximately 4 years ]
    Proportion of participants with AML or MDS who achieve CR

  8. Complete remission with incomplete blood count recovery (CRi) rate [ Time Frame: Up to approximately 4 years ]
    Proportion of participants with AML who achieve CRi

  9. 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

  10. Hematologic response (HI) rate [ Time Frame: Up to approximately 4 years ]
    Proportion of MDS participants with HI

  11. 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, CRh, or PR.

  12. 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

  13. Duration of response (DOR) [ Time Frame: Up to approximately 4 years ]
    For AML, the time from first CR, CRi, or 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, or CRh to the first documentation of disease progression, start of new therapy, or death due to any cause.

  14. 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

  15. 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.

  16. MRD-negative ORR [ Time Frame: Up to approximately 4 years ]
    Proporation of participants with AML or MDS who achieve MRD-negative ORR

  17. Time to response (TTR) [ Time Frame: Up to approximately 4 years ]
    Time from start of study treatment to the first documentation of objective response

  18. 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

  19. Maintenance of TI [ Time Frame: Up to approximately 4 years ]
    Number of subjects who were TI at baseline and maintain TI post-baseline



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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% 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 (e.g., G-CSF, erythropoietin and thrombopoietin) 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 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
  • History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04227847


Contacts
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Contact: Seagen Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35249
Contact: Hilary Avery    205-934-7167    hilaryavery@uabmc.edu   
Principal Investigator: Pankit Vachhani         
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010-3000
Contact: Lucia Magos    626-256-4673    lmagos@coh.org   
Principal Investigator: Ahmed M Aribi         
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: James Vick    720-754-4800    James.Vick@sarahcannon.com   
Principal Investigator: Marcello Rotta         
United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40207
Contact: Joshua Roberts    502-899-2673      
Principal Investigator: Don A Stevens         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Meghan Burke    617-726-1599      
Principal Investigator: Amir Fathi         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Kayla Loycano    617-667-9920      
Principal Investigator: Jessica Liegel         
United States, Michigan
Karmanos Cancer Institute / Wayne State University Recruiting
Detroit, Michigan, United States, 48201
Contact: Mary Domagalski    313-576-9767    domagalm@karmanos.org   
Principal Investigator: Jay Yang         
United States, Ohio
Case Western Reserve University / University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Sarah Housour    216-286-7082    Sarah.Housour@uhhospitals.org   
Principal Investigator: Benjamin K Tomlinson         
Cleveland Clinic, The Recruiting
Cleveland, Ohio, United States, 44195
Contact: Taussig Research group email    866-223-8100    TaussigResearch@ccf.org   
Principal Investigator: Anjali Advani         
James Cancer Hospital / Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Shayla Thompson    614-293-5655      
Principal Investigator: Alice Mims         
Principal Investigator: Nicole Grieselhuber         
United States, South Carolina
Medical University of South Carolina/Hollings Cancer Center Recruiting
Charleston, South Carolina, United States, 29425
Contact: Shanta Salzer    843-792-1463      
Principal Investigator: Robert K Stuart         
Principal Investigator: Praneeth Baratam         
Saint Francis Hospital / Bon Secours - South Carolina Recruiting
Greenville, South Carolina, United States, 29607
Contact: Sharon (Nikki) N Thompson    864-603-6238      
Principal Investigator: Howland Crosswell         
Principal Investigator: Sharif S Khan         
United States, Tennessee
Tennessee Oncology-Nashville/Sarah Cannon Research Institute Completed
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology - Fort Worth Recruiting
Dallas, Texas, United States, 75246
Contact: Joyce Ghormley    214-818-8961      
Principal Investigator: Edward J Pearson         
MD Anderson Cancer Center / University of Texas Recruiting
Houston, Texas, United States, 77030-4095
Contact: Heather Schneider    713-792-4478    hnschneider@mdanderson.org   
Principal Investigator: Guillermo Garcia-Manero         
Netherlands
Leids Universitair Medisch Centrum ( LUMC) Recruiting
Leiden, Other, Netherlands, 2333 ZA
Principal Investigator: Hendrik J Veelken         
Sponsors and Collaborators
Seagen Inc.
Investigators
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Study Director: Phoenix Ho, MD Seagen Inc.
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Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT04227847    
Other Study ID Numbers: SGNS70-101
2019-001917-18 ( EudraCT Number )
First Posted: January 14, 2020    Key Record Dates
Last Update Posted: May 10, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seagen Inc.:
Seattle Genetics