Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

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.

Official Title

A Phase 1 Study of SEA-CD70 in Myeloid Malignancies

Details

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.

Keywords

Myelodyspastic Syndrome Acute Myeloid Leukemia Seattle Genetics SEA-CD70

Eligibility

For people ages 18 years and up

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

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

Locations

  • City of Hope National Medical Center accepting new patients
    Duarte California 91010-3000 United States
  • Colorado Blood Cancer Institute accepting new patients
    Denver Colorado 80218 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Seagen Inc.
ID
NCT04227847
Phase
Phase 1 research study
Study Type
Interventional
Participants
Expecting 60 study participants
Last Updated