A Phase 1 Study of SEA-CD70 in Myeloid Malignancies

Recruiting

Conditions: Acute Myeloid Leukemia
Myelodisplastic syndrome
10024324

Registration Number: NL-OMON54392

Lead Sponsor: Seagen Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 8

Inclusion Criteria

SEA-CD70 dose-escalation cohort in relapsed/refractory (HMA-failure) MDS, Part
A:
1. Subjects 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 (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)
* 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 hematologic improvement [HI]
per 2006 IWG criteria) after at least 6 cycles of azacitidine (or equivalent
oral HMA) or 4 cycles of decitabine (or equivalent oral 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).
* Subjects with isolated 5q-/5q- syndrome must have progressed, failed,
relapsed, or not tolerated lenalidomide in addition to HMA.
2. 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.
3. Age >=18 years.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1

SEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS, Part B:
5. Subjects with cytologically/histologically confirmed MDS according to the
2016 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)
* 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 equivalent oral HMA) or 4 cycles of
decitabine (or equivalent oral 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).
* Subjects with isolated 5q-/5q- syndrome must have progressed, failed,
relapsed, or not tolerated lenalidomide in addition to HMA.
6. 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.
7. At least one cytopenia (ANC <1800/µL or platelet count <100,000/µL or
hemoglobin [Hgb] <10 g/dL).
8. Age >=18 years.
9. ECOG Performance Status of 0-2

SEA-CD70 expansio

Exclusion Criteria

1. 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 (e.g., 5-year OS >=90%), such as adequately treated carcinoma in situ of
the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal
carcinoma in situ, or Stage I uterine cancer.
2. Previous exposure to CD70-targeted agents.
3. Prior allogeneic hematopoietic stem cell transplant, for any condition.
4. Central nervous system leukemia based on imaging or documented positive
cytology in cerebral spinal fluid.
5. Any uncontrolled Grade 3 or higher (per the National Cancer Institute*s
Common Terminology Criteria for Adverse Events [NCI CTCAE], version 5.0) 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.
6. 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. Subjects must have recovered adequately from the surgery/injury, or
complications thereof, prior to starting treatment.
7. 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.
8. Known to be positive for human immunodeficiency virus (HIV).
9. Known active or latent tuberculosis.
10. History of clinically significant sickle cell anemia, autoimmune hemolytic
anemia, or idiopathic thrombocytopenic purpura.
11. History of clinically significant chronic liver disease (e.g., liver
cirrhosis) and/or ongoing alcohol abuse.
12. 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 (Appendix F) within 6
months prior to their first dose of SEA-CD70.
13. 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.
14. Subjects with either of the following:
a. 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 (inhaled, topical, intraocular, intranasal, and
intraarticular steroids are permitted in the absence of active immune disease,
and steroid premedication for prevention of hypersensitivity reactions to
radiographic contrast is permitted).
b. Active known or suspected clinically significant autoimmune disease or
cl