HM2023-05: GTB-3650 Trike for High Risk MDS and R/R AML

Inclusion criteria

• Diagnosis of a high risk myelodysplastic syndromes (MDS), treatment related MDS, OR relapsed/refractory acute myelogenous leukemia (AML).
• Absolute lymphocyte count (ALC) ≥ 200 cells/µL OR absolute circulating CD56+/CD3- NK cell count >25 cells/µL within the 14 days prior to Cycle 1 Day 1.
• Peripheral blasts ≤20,000 at the time of treatment start. Hydroxyurea may be used up to Day 1 of the 1st cycle to achieve this threshold and continued for the 1st two weeks of Cycle 1 to maintain it.
• Karnofsky performance status ≥ 70%
• Adequate organ function within 14 days (30 days for cardiac) of Cycle 1 Day 1
• Sexually active persons of childbearing potential or persons with partners of childbearing potential must agree to use a highly effective form of contraception during study treatment and for at least 4 months after the last dose of GTB-3650. Non-childbearing is defined as >1 year postmenopausal or surgically sterilized.

-For the Dose Finding Component Only: Must agree to stay within a 60- minute drive of the Study Center through the Cycle 1 Day 29 visit (end of the Dose Limiting Toxicity period).

• Provides voluntary written consent prior to the performance of any research related activity.
• Pulmonary: room air 0 2 saturation at ≥ 95%

Exclusion criteria

• Pregnant or breast-feeding. The effect of GTB-3650 TriKE on the fetus is unknown. Persons of childbearing potential must have a negative serum or urine test within 7 days prior to Cycle 1 Day 1 to rule out pregnancy.
• A candidate for hematopoietic stem cell transplant (HSCT) or newly relapsed after HSCT (e.g. no post-HSCT therapy given).
• Bi-phenotypic acute leukemia or mixed lineage leukemia.
• Acute promyelocytic leukemia (APL).
• No anticancer therapy within 14 days of Cycle 1 Day 1; any AEs from therapy given prior must have resolved to Grade 1 or baseline
• New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan unless cleared for study by Pulmonary. Infiltrates attributed to infection must be stable/improving with associated clinical improvement after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
• Active systemic infection requiring parenteral antibiotic therapy. Any prior systemic infections must have resolved following optimal therapy.
• Known history of HIV.
• Active Hepatitis B or Hepatitis C (virus detectable by PCR) - chronic asymptomatic viral hepatitis is allowed.
• Positive test results from chronic hepatitis B infection (defined as positive HBsAg serology) and/or positive test results for hepatitis C (HCV antibody serology test).
• Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer currently in complete remission, or any other cancer from which the patient has been disease-free for 1 year
• Active central nervous system (CNS) malignancy or symptoms of CNS spread or administration of IT chemotherapy within 14 days prior to Day 1.
• Extramedullary disease causing symptoms and/or involving the CNS or spinal canal - asymptomatic extramedullary disease outside the CNS and spinal canal is eligible provided the marrow has measurable disease.
• Known autoimmune disease requiring active treatment with steroids or other immunosuppressive medications within 14 days before Cycle 1 Day. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Persons with a condition requiring systemic treatment with steroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before Cycle 1 Day 1.
• The potential risk of QT/QTc prolongation is unknown in humans receiving

TriKE therefore either of the following is an exclusion criteria:

• QTc interval > 480 msec at screening
• A family history of long QT syndrome
• Psychiatric illness/social situations that, in the judgement of the enrolling Investigator, would limit compliance with study requirements.
• Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient from participating in this study.