Health Condition 1: C858- Other specified types of non-Hodgkin lymphoma
Conditions
Interventions
Intervention1: AUR104:5mg and 20mg Tablets: Once or Twice Daily approximately 6 cycles (ie.,168 days)
Control Intervention1: Not Applicable: Not Applicable
Sponsors
Aurigene Oncology Limited
Aurigene Oncology Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1) Males and females >= 18 years of age. 2) Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1. 3) Acceptable bone marrow and organ function at screening as described below: - ANC >= 1000/μL (without WBC growth factor support) - Platelet count: For patients with CLL >= 50,000/μL, For patients with lymphomas >= 75,000/μL without bone marrow involvement and >= 50,000/μL with bone marrow involvement. These thresholds should be qualified without current transfusion support. - Hemoglobin >= 9 g/dL (Transfusion is allowed to achieve this Hb). - Total Bilirubin - AST (SGOT) - ALT (SGPT) - Creatinine clearance (CrCl) >= 60 mL/min (either measured or estimated by the Cockcroft-Gault formula). Cockcroft-Gault formula for estimated creatinine clearance (eCrCl):(140 â?? Age) Ã? Weight (kg) Ã? (0.85 if Female)/(72 Ã? serum creatinine in mg/dL). 4) Ability to swallow and retain oral medications. 5) Histopathological diagnosis of Non-Hodgkin Lymphoma (NHL) or Chronic Lymphocytic Leukemia (CLL) or Hodgkin disease. Note: 5a. The lymphoma should be either in Stage III or IV according to Lugano classification at screening. 5b. The lymphomas included in this study must fall within one of the following 2017 World Health Organization categories except lymphoma mentioned in Exclusion criterion #5: -Mature B-cell neoplasms (excluding plasma cell neoplasms, heavy chain disease, and primary central nervous system [CNS] lymphoma). -Mature T- and NK-cell neoplasms. -Hodgkin lymphomas. 5c. The CLL should be Binet Stage C/Rai stage III or IV, as per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines. 6) In the case of patients who have lymphoid malignancies for which high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) is considered standard curative therapy, eligibility for this study requires that the subjectâ??s disease has relapsed after HD-ASCT, or the subject is not eligible for HD-ASCT, or the subject has refused HD-ASCT. 7) In the case of patients who have lymphoid malignancies for which CAR-T therapy is indicated, eligibility for this study requires that the disease has relapsed after CAR-T, or the patient is not eligible for CAR-T, or the patient has refused CAR-T, or the CAR-T is not available locally. 8) Evidence of measurable disease as per Lugano Criteria for Lymphoma or evidence of measurable disease as per iwCLL Criteria for CLL. Note: Patients with Small Lymphocytic Lymphoma (SLL) alone or in combination with CLL are allowed. 9) Standard curative measures do not exist, and the patient must have exhausted all effective therapies available locally. At a minimum, the patients must have relapsed or refractory disease to at least 2 prior lines of systemic therapies for NHL or CLL, or Hodgkinâ??s disease. Note: Any cancer patient with access to any effective therapy locally must not be enrolled.
Exclusion criteria
Exclusion criteria: 1) Systemic anti-cancer therapy, such as chemotherapy, biological therapy, or immunomodulatory drug therapy, received within the past 28 days or 5 half-lives, whichever is longer, from Cycle 1 Day 1 of the study. Note: Concomitant use of low-dose prednisone (up to 10 mg/day) is allowed. 2) Presence of acute or chronic toxicity resulting from prior anti-cancer treatment, except for alopecia or nail changes that have not resolved to Grade 3) Definitive Radiotherapy within the last 21 days of Cycle 1 Day 1 (limited field palliative radiation is allowed and no restrictions during the screening period or during the trial). 4) Use of any investigational agent within 28 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1. 5) Patients with Burkittâ??s lymphoma, Burkitt-like lymphoma, post-transplant lymphoproliferative disease, primary mediastinal large-B cell lymphoma, cutaneous lymphomas, mycosis fungoides (MF), or Sezary syndrome (SS). 6) Known symptomatic or untreated or recently treated ( 7) Patients with lymphoma requiring immediate cytoreductive therapy. 8) Patients with low-grade or indolent lymphoma not meeting conventional criteria for treatment. 9) Elevated Serum cardiac Troponin I or troponin T more than ULN at screening. 10) Serum magnesium and calcium levels more than 1.2 x ULN or less than 0.8x LLN. 11) Serum Potassium more than 1.0x ULN or less than 1.0x LLN. Note: Patients experiencing hypokalemia are permitted to undergo treatment to attain normal potassium levels during the screening period. 12) Mean Heart Rate less than 60 at screening or Cycle 1 Day 1 (to be recorded at least 3 times at least 5 minutes apart) in ECG. 13) Left ventricular ejection fraction (LVEF) less than 50% as determined by an echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan. 14) QTcF (Fridericia) interval more than 450 ms for patients on ECG at screening and/or at Cycle 1 Day 1. 15) Uncontrolled arterial hypertension defined as supine SBP of >= 140 mm Hg AND/OR supine DBP >= 90 mmHg on stable doses of three or lesser different classes of antihypertensive drugs. Notes: - Patients taking 4 or more classes of antihypertensives are excluded. Diuretics (such as furosemide or spironolactone) are considered as one class of anti-hypertensives. - The blood pressure has to be recorded 3 times at least 10 minutes apart during Screening and Cycle 1 Day 1 (before dosing) in the supine position. Among these recordings, a single instance of SBP >=140 mm Hg or DBP >= 90 mmHg will exclude the patient. Note: A patient excluded on these criteria can be re-screened after optimal BP management. 16) Current or past history of heart failure (NYHA Class 2 or higher) 17) Having a history of moderate to severe cardiovascular disease including unstable angina, myocardial infarction, cerebrovascular accident, or transient ischemic attack (TIA), within 1 year prior to Cycle 1 Day 1. 18) Ongoing cardiac arrhythmias or conduction blocks. 19) History of any ventricular arrhythmia including supraventricular or ventricular premature contract
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoints - First cycle DLT. - Safety and tolerability of AUR104 as measured by NCI CTCAE v 5.0. - PK parameters including but not limited to AUC(0-12), AUC (0-24), AUC0-t, Cmax, Cmin, Tmax, MRT, and t½.Timepoint: 28 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory Endpoints - PD biomarkers. - Efficacy assessments of overall response rates (ORR), duration of response (DOR), Progression Free Survival (PFS), etc., as measured by Lugano Criteria for NHL/ Hodgkin lymphoma or iwCLL criteria for CLL.Timepoint: PD biomarkers: 28 days Efficacy: Baseline, Cycle 2, 4, 6, 9, 12 and then every 3 months thereafter | — |
Countries
India
Contacts
Public ContactOduru Suresh Reddy
Aurigene Oncology Limited
Outcome results
None listed