Clinical Trials /

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

NCT04227847

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Secondary Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies
  • Official Title: A Phase 1 Study of SEA-CD70 in Myeloid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: SGNS70-101
  • SECONDARY ID: 2019-001917-18
  • NCT ID: NCT04227847

Conditions

  • Myelodyspastic Syndrome
  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
SEA-CD70Part A

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Part AExperimentalSEA-CD70 dose escalation cohort in relapsed/refractory (HMA-failure) MDS
  • SEA-CD70
Part BExperimentalSEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS
  • SEA-CD70
Part CExperimentalSEA-CD70 expansion cohort in relapsed/refractory AML
  • SEA-CD70

Eligibility Criteria

        Part A Inclusion Criteria

          -  Subjects with cytologically/histologically confirmed myelodysplastic syndrome (MDS)
             according to the World Health Organization (WHO) classification with the following:

               -  5%-20% bone marrow blasts.

               -  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 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).

                    -  Subjects 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

          -  Subjects with cytologically/histologically confirmed MDS according to the WHO
             classification with the following:

               -  5%-20% bone marrow blasts.

               -  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).

                    -  Subjects 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

          -  Subjects 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.

          -  Subjects who have experienced major surgery (defined as requiring general anesthesia
             and hospitalization for >24 hours) or significant traumatic injury that would place
             the subject 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).
             Subjects 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.

          -  Subjects 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

          -  Subjects who are breastfeeding, pregnant, or planning to become pregnant from time of
             informed consent until 2 months after final dose of study drug

          -  Known hypersensitivity to any excipient contained in the drug formulation of SEA-CD70

          -  Estimated life expectancy <12 weeks
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events (AEs)
Time Frame:Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Genetics, Inc.

Last Updated

January 10, 2020