Details

Details

Title A phase 1b dose-escalation study of SGN-CD33A in combination with standard-of-care for patients with newly diagnosed acute myeloid leukemia (AML)

IRB SEGE1914

CC 15-144

Hospital Main Campus

Phase Phase 1

Disease Leukemia - Acute Myeloid (AML)

Drug SGN-CD33A

Description

Description

Primary Objectives
  • Evaluate safety and tolerability of SGN-CD33A in combination with standard induction and consolidation therapy and as maintenance monotherapy
  • Identify MTD of SGN-CD33A in combination with standard induction and consolidation therapy and determine the recommended dose for maintenance monotherapy
Secondary Objectives
  • To assess the antitumor activity of SGN-CD33A
  • To evaluate the pharmacokinetics (PK) of SGN-CD33A
  • To evaluate the immunogenicity of SGN-CD33A
Additional Objectives
  • To evaluate minimal residual disease (MRD) after induction, consolidation, and maintenance therapy with SGN-CD33A
  • To explore the relationship between the PK of SGN-CD33A, CD33 saturation, and antitumor response
  • To explore the relationship between molecular disease characteristics with efficacy endpoints
Inclusion Criteria

Inclusion Criteria

  1. All subtypes of AML, with the exception of acute promyelocytic leukemia (APL).
  2. The following part-specific criteria:
    1. Parts A, D, E, and F: Eligible to receive induction therapy.
    2. Part B: Achieved a CR/CRi with standard induction therapy and eligible to receive consolidation.
    3. Part C, all enrolled:
      • Completed induction therapy and, if indicated, consolidation therapy, and in CR with documented hematopoietic and peripheral blood count recovery (ANC ≥1000/mm3 and transfusion independent platelets ≥50,000/mm3).
    4. Part C, post allogeneic stem cell transplant (alloSCT):
      • In CR1 with documented hematopoietic and peripheral blood count recovery (ANC ≥1000/mm3 and transfusion independent platelets ≥50,000/mm3).
      • At least 60 days but no more than 100 days post-transplant.
  3. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 (See Appendix D).
  4. Age 18-65 years. There is no upper age limit for patients enrolled to Part C.
  5. The following baseline laboratory data:
    • Serum bilirubin of ≤1.5x upper limit of normal (ULN) or ≤3x ULN for patients with Gilbert's disease
    • serum creatinine ≤2.5x ULN and creatinine clearance ≥30 mL/min
    • alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x ULN
  6. Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (β-hCG) pregnancy test result within 7 days prior to the first dose of SGN-CD33A and must agree to use an effective contraception method during the study and for 6 months following the last dose of study drug. Females of nonchildbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
  7. Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of study drug.
  8. Patients must provide written informed consent.
Exclusion Criteria

Exclusion Criteria

  1. Parts A and B dose-escalation only: previously received treatment for antecedent myelodysplastic syndrome (MDS) such as hypomethylating agents, etc.
  2. History of confirmed or suspected diagnosis of idiopathic pulmonary fibrosis or unclassifiable interstitial lung disease.
  3. Central nervous system leukemia strongly suspected based on altered neurologic status or documented by positive cytology in cerebral spinal fluid.
  4. Receipt of prior therapy for AML, with the exception of induction therapy for patients in Part B, induction with or without consolidation and prior allogeneic stem cell transplant (alloSCT) for patients in Part C. Patients in Part B and C may not have received SGNCD33A previously. Hydroxyurea or 6-mercaptopurine used for cytoreduction may be given up to 1 day prior to treatment. Prophylactic intrathecal chemotherapy may be administered prior to study treatment.
  5. Left ventricular ejection fraction less than 45%, or previous treatment with complete cumulative doses of doxorubicin or other anthracyclines.
  6. Any uncontrolled Grade 3 or higher (per NCI CTCAE, Version 4.03) viral, bacterial, or fungal infection ongoing prior to the first dose of any component of study treatment. Antimicrobial prophylaxis or ongoing treatment of resolving/controlled infection is permitted.
  7. 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 (NYHA) Class III-IV within 6 months prior to the first dose of any component of study treatment (See Appendix E).
  8. Any known history of Hepatitis B (HBSAg positive), Hepatitis C, or HIV.
  9. Current therapy with other systemic anti-neoplastic, immunosuppressive, or investigational agents, other than as described in Section 5.3.2
  10. Known hypersensitivity to monoclonal antibodies or excipient contained in the drug formulations of SGN-CD33A, cytarabine, daunorubicin, or idarubicin, as applicable to the appropriate cohort.
  11. Females who are breastfeeding.
  12. History of another primary invasive malignancy that has not been in remission for at least 3 years. The following are exempt from the 3-year limit: curatively treated nonmelanoma skin cancer; curatively treated, localized prostate cancer and low grade prostate cancer suitable for active surveillance.
  13. History of myeloproliferative neoplasm (MPN).
  14. Part C, post alloSCT:
    • Active graft -versus -host disease (GVHD) Grade 2 or higher.
    • History of hepatic GVHD.
    • Concurrent use of corticosteroids equivalent of prednisone at a dose of >0.5 mg/kg.