Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
by Caspian Oliai (ucla)

Description

Summary

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.

Official Title

A Phase 1 Study of SEA-CD70 in Myeloid Malignancies

Details

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.

Keywords

Myelodyspastic Syndrome, Acute Myeloid Leukemia, Seattle Genetics, Azacitidine, SEA-CD70

Eligibility

For people ages 18 years and up

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

Locations

  • UCLA Department of Medicine - Hematology & Oncology accepting new patients
    Los Angeles California 90095 United States
  • City of Hope National Medical Center accepting new patients
    Duarte California 91010-3000 United States

Lead Scientist at University of California Health

  • Caspian Oliai (ucla)
    HS Assistant Clinical Professor, Medicine. Authored (or co-authored) 16 research publications

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 140 study participants
Last Updated