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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
Study Type
Phase
Eligibility
Gender
Healthy Volunteers
Minimum Age
Maximum Age
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.
- Measurable disease per WHO MDS with excess blasts criteria as defined either:
- 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.
- Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria as defined either:
- 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
- MDS with excess blasts (MDS-EB), defined as either:
- 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)
- Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria as defined either:
- 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
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Study Stats
Protocol No.
21-001520
Category
Leukemia
Principal Investigator
Contact
Location
- UCLA Westwood