Safety, PK, PD, Clinical Activity of KT-333 in Adult Patients With Refractory Lymphoma, Large Granular Lymphocytic Leukemia, Solid Tumors
Non Hodgkin Lymphoma (NHL), Peripheral T-cell Lymphoma (PTCL), Cutaneous T-Cell Lymphoma (CTCL)
About this trial
This is an interventional treatment trial for Non Hodgkin Lymphoma (NHL)
Eligibility Criteria
Inclusion Criteria:
- Phase 1a Only: Histologically or pathologically confirmed Lymphomas (including Hodgkin's, B-cell, T-cell, Small Lymphocytic, or NK-cell Lymphomas and LGL-L) and solid tumors with the exception of chronic lymphocytic leukemia (CLL) Note: Patients with indolent NHL and small lymphocytic lymphoma (SLL) are only eligible if not require immediate cytoreductive therapy or if there are no available treatments with potential benefit.
- Phase 1b Only: Histologically or pathologically confirmed PTCL, CTCL, LGL-L [T-cell LGL-L or Chronic Lymphoproliferative Disorder of NK-cells (CLPD-NK)], or solid tumors.
- Fresh or archival formalin fixed paraffin embedded (FFPE) tumor tissue or 15 slides preferably collected within 6 months or 2 years prior to first dose of the study drug (for lymphoma and solid tumor patients respectively).
- Phase 1a only: Lymphoma and Solid Tumor: Relapsed and/or refractory disease to at least 2 prior systemic standard of care treatments or for whom standard therapies are not available.
- Phase 1a: LGL-L: Relapsed and/or refractory disease to at least 1 prior systemic standard of care treatment or for whom standard therapies are not available.
- Phase 1b only: All disease types: Relapsed and/or refractory disease to at least 1 prior systemic standard of care treatments or for whom standard therapies are not available.
LGL-L patients only (hematology specific criteria):
One of the following:
- Severe neutropenia < 500/mm3, or,
- Symptomatic anemia and/or,
- Transfusion-dependent anemia.
- ANC ≥ 200/μL at Screening and C1D1 (pre dose)
- Platelet count ≥ 100,000/μL (assessed ≥ 7 days following last platelet transfusion in patients with thrombocytopenia requiring platelets).
LGL-L Patients Only (baseline disease characteristics):
- CD3+CD8+ cell population >650/mm3;
- CD3+CD8+CD57+ population >500/mm3;
- Presence of a clonal T-cell receptor (within 1 month of diagnosis);
- Note: patients with T-LGLL may be included with PI approval even if CD3+CD8+ cell population is<650/mm3 or CD3+CD8+CD57+ population is <500/mm3, though +TCR is required;
- Natural-Killer (NK) LGL is also permitted, provided there is a clonal NK-cell population noted with>500 cells/mm3
- PTCL and solid tumors Only: Measurable disease at Screening. Solid tumor patients with non-measurable disease are allowed in Phase1a
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening and C1D1 (pre-dose).
- Adequate bone marrow function at Screening and C1D1 (pre-dose) for all patients except those with LGL-L Adequate liver/kidney organ function at Screening and C1D1 (pre-dose) for all patients. Women of childbearing potential (WOCBP) must agree to use highly effective contraceptive methods for the duration of study treatment and 6 months after the last dose of KT333.
Exclusion Criteria:
- History or suspicion of central nervous system (CNS) metastases.
- Diagnosis of Chronic Lymphocytic Leukemia (CLL).
- History of or active concurrent malignancy other than lymphoma or solid tumors unless the patient has been disease-free for ≥ 2 years.
- Patient has not recovered from any clinically significant adverse events (AEs) of previous treatments to pretreatment baseline or Grade 1 prior to first dose of study drug.
- Ongoing unstable cardiovascular function.
- Autologous hematopoietic stem cell transplant less than 3 months prior to first dose of study drug.
- Prior allogenic hematopoietic or bone marrow transplant.
Sites / Locations
- UC Irvine Health-Chao Family Comprehensive Cancer CenterRecruiting
- Norton Cancer InstituteRecruiting
- Henry Ford HospitalRecruiting
- Hackensack University Medical Center, John Theurer Cancer CenterRecruiting
- Montefiore Medical Center, The University Hospital for Albert Einstein College of MedicineRecruiting
- The Christ Hospital Cancer CenterRecruiting
- Ohio State University Wexner Medical CenterRecruiting
- Abramson Cancer Center of the University of Pennsylvania Perelman Center for Advanced MedicineRecruiting
- Thomas Jefferson University, Sidney Kimmel Cancer CenterRecruiting
- Rhode Island HospitalRecruiting
- MD Anderson Cancer CenterRecruiting
- University of Virginia, Emily Couric Cancer CenterRecruiting
- University of WA/Seattle Cancer Care AllianceRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Phase 1a Dose Escalation Lymphomas
Phase 1a Dose Escalation Solid Tumors
Phase 1b Dose Expansion PTCL
Phase 1b Dose Expansion CTCL
Phase 1b Dose Expansion LGL-L
Phase 1b Dose Expansion Solid Tumor
Phase 1a Dose Escalation LGL-L
Phase 1a Dose Escalation T-PLL
KT-333 dosed IV weekly in 28 day cycles
KT-333 dosed IV weekly in 28 day cycles
KT-333 dosed IV weekly in 28 day cycles
KT-333 dosed IV weekly in 28 day cycles
KT-333 dosed IV weekly in 28 day cycles
KT-333 dosed IV weekly in 28 day cycles
KT-333 dosed IV weekly in 28 day cycles
KT-333 dosed IV weekly in 28 day cycles