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

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Brief 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.

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase I

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
18 Years
Maximum Age
N/A

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

Join this Trial

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Study Stats
Protocol No.
21-001520
Category
Hematology-Oncology
Oncology
Contact
Bruck Habtemariam
Location
  • UCLA Westwood
For Providers
NCT No.
NCT04227847
For detailed technical eligibility, visit ClinicalTrials.gov.