| Eligibility |
Inclusion Criteria:
1. Men and women = 18 years of age with histologically or cytologically confirmed R/R
B-NHL, including but not limited to chronic lymphocytic leukemia/small lymphocytic
leukemia (CLL/SLL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL),
marginal zone lymphoma (MZL), diffuse large-b-cell lymphomas (DLBCL), and transformed
lymphoma who failed or are intolerant to = 1 prior standard of care regimens.
Notes:
- Patients with prior treatment of BTK inhibitors are eligible
- Patients with low grade lymphoma must be progressing and requiring treatment:
- Patients with CLL must have disease requiring treatment as specified in 2018
IWCLL Guidelines (Appendix 5)
- Patients with B-cell NHL must have measurable disease per 2014 Lugano
Classification (Appendix 6)
- Patients with WM must have minimum serum immunoglobulin M (IgM) level of = 2
times the upper limit of normal (ULN)
2. Body weight = 40 kg
3. Eastern Cooperative Oncology Group (ECOG) performance status of = 2
4. Adequate organ function, defined by the following laboratory parameters:
- Hematologic:
- Absolute neutrophil count (ANC) = 750/ul, unless due to bone marrow
involvement due to disease
- Platelets = 50,000/ul without transfusion within 7 days
- Hemoglobin = 80 mg/dl without transfusion within 7 days
- Coagulation:
- Prothrombin time (PT) = 1.5 × ULN
- Activated partial thromboplastin time (aPTT) = 1.5 × ULN
- Renal function:
o Creatinine clearance = 60 mL/min estimated glomerular filtration rate based on
Cockcroft-Gault formula or 24-hour urine collection
- Liver function:
- Total bilirubin = 1.5 × ULN (unless due to Gilbert's disease)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2.5 ×
ULN unless disease-related
5. Agreement to use contraception during the study and until at least 6 months after the
last dose of study drug if sexually active and able to bear children
6. Willing and able to participate in all required evaluations and procedures in the
study protocol including swallowing tablets without difficulty
7. Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information (in accordance
with national and local subject privacy regulations)
Exclusion Criteria:
1. Women who are pregnant or lactating
2. Prior malignancy, except for adequately treated basal cell or squamous cell skin
cancer, in situ cervical cancer, or other cancer from which the subject has been
disease-free for at least 2 years or which will not limit survival to < 2 years (Note:
these cases must be discussed with the Medical Monitor and/or Investigator)
3. A life-threatening illness, medical condition, or organ system dysfunction which, in
the investigator's opinion, could compromise the subject's safety, interfere with the
absorption or metabolism of TT-01488, or put the study outcomes at undue risk
4. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias,
congestive heart failure, or myocardial infarction within 6 months of screening, or
significant screening ECG abnormalities including left bundle branch block, 2nd degree
AV block type II, 3rd degree block, bradycardia, and corrected QT interval using
Fridericia's Formula (QTcF) > 470 msec, or any Class 3 or 4 cardiac disease as defined
by the New York Heart Association Functional Classification
5. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel or ulcerative colitis, symptomatic
inflammatory bowel disease, or partial or complete bowel obstruction
6. Any immunotherapy, , radiotherapy (limited-field radiation for palliation within 7
days), or experimental therapy within 4 weeks, or 5-half lives for chemotherapy and
small molecule agents (whichever is shorter), before first dose of study drug
(corticosteroids for disease-related symptoms allowed but require 1-week washout
before study drug administration)
7. History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen
receptor-modified T-cell (CAR-T) therapy within the past 60 days or with any of the
following:
- Active graft versus host disease (GvHD);
- Cytopenias from incomplete blood cell count recovery post-transplant;
- Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms
of neurotoxicity > Grade 1 from CAR-T therapy;
- Ongoing immunosuppressive therapy
8. Concomitant use of prohibited medications(Section 6.4.2), including:
- Therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative
anticoagulants
- Medications with known risk to cause QT prolongation or Torsades de pointes
- Strong CYP3A inhibitors and inducers (must be discontinued for at least 14 days
or 5 half-lives, whichever is longer, before study treatment)
- Proton pump inhibitors, histamine-2 blockers (H2 blockers), and locally acting
antacids (Note: For patients who are dependent upon this class of medications,
patients may be considered after consulting with the study investigator and
Sponsor. See Section 6.4.2 for more details).
9. Central nervous system involvement by lymphoma
10. Grade = 2 toxicity (other than alopecia) continuing from prior anticancer therapy,
including radiation
11. Known history of Human Immunodeficiency Virus (HIV) or active infection with
Cytomegalovirus (CMV), Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV), or any
uncontrolled active systemic infection
12. Major surgery within 4 weeks before first dose of study drug
|
