The purpose of this study is to evaluate the safety and tolerability of MT-3724 in subjects with relapsed or refractory B-Cell NHL or relapsed and refractory CLL (Part 1 only) and relapsed and refractory DLBCL (Part 2 and Part 3). Part 3 evaluates the efficacy of MT-3724.
This is a three-part Phase 2 study Part 1: (MT-3724 Dose Escalation) Define the maximum tolerated dose (MTD) of MT-3724 \[Completed\] Part 2: (MTD Expansion Cohort) Confirm the safety and tolerability of the MTD of MT-3724 in the MTD Expansion Cohort. Part 3: (Phase 2 MTD Expansion Cohort) Determine the efficacy of MT-3724 as monotherapy in subjects with relapsed or refractory DLBCL based on the overall response rate (ORR) by the revised Lugano Classification for Lymphoma adjusted according to LYRIC. It is anticipated that up to 100 patients will be enrolled in Part 3. Treatment will continue for up to six 21 days cycles. If the subject exhibits SD, CR or PR after the end of Cycle 6 and the investigator determines that the benefit-risk ratio is favorable, then the treatment with MT-3724 may be continued after discussion with the sponsor.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Intravenous dosing Days 1, 3, 5, 8, 10 and 12; MT-3724 infusion over 2 hours on each dosing day over 28 day initial cycle and then 21 week repeat cycles for up to 5 total cycles.
Intravenous dosing on Days 1, 3, 5, 8, 10 and 12; MT-3724 infusion over 1 hour on each dosing day over 21 day cycle up to 6 cycles and then can be continued for 6 additional cycles.
University of Arizona
Tucson, Arizona, United States
Innovative Clinical Research Institute, LLC
Whittier, California, United States
21st Century Oncology - Jacksonville
Jacksonville, Florida, United States
Orlando Health, Inc.
Orlando, Florida, United States
Orlando Health, Inc.
Orlando, Florida, United States
Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724
The MTD is defined to be the dose cohort below which participants experience dose-limiting toxicities during cycle 1. Dose-limiting toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time frame: Days 1, 3, 5, 8, 10 and 12
Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274
Blood samples were collected at indicated timepoints for the determination of Cmax of MT-3274.
Time frame: Part 1 and 2 : Days 1, 3 and 12
Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724
Blood samples were collected at indicated timepoints for the determination of tmax.
Time frame: Part 1 and 2: Days 1, 3 and 12
Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724
Blood samples were collected at indicated timepoints for the determination of AUC (0-4), AUC (0-infinity) and AUClast.
Time frame: Part 1 and 2: Days 1, 3 and 12
Part 1 and 2: Half Life (t1/2) of MT-3724
Blood samples were collected at indicated timepoints for the analysis of t1/2 of MT-3724.
Time frame: Part 1 and 2: Days 1, 3 and 12
Part 1 and 2: Volume of Distribution (Vz) of MT-3724
Blood samples were collected at indicated timepoints for the analysis of Vz of MT-3724.
Time frame: Part 1 and 2: Days 1, 3 and 12
Part 1 and 2: Clearance (CL) of MT-3724
Blood samples were collected at indicated timepoints for the analysis of CL of MT-3724.
Time frame: Part 1 and 2: Days 1, 3 and 12
Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes
CD19+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus
Time frame: Part 1 and 2: Cycle 1: Days 8 and 23; Cycle 3: Day1; Cycle 5: Day 1 and Day 120 (end of study)
Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed
Blood samples were collected to analyze the presence of ADA that bind MT-3724. Number of participants with positive ADA confirmed has been presented.
Time frame: Part 1 and 2: Cycle 1, Day 23; Cycle 2, Day 1; Cycle 3, Day 1; Cycle 4, Day 1; Cycle 5, Day 1 and Day 120 (end of study)
Part 3: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs
An adverse event is any untoward medical occurrence or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention.
Time frame: Up to Day 45
Part 3: Number of Participants With Clinically Significant Laboratory Parameters
Blood samples were collected at indicated timepoints for the analysis of laboratory parameters.
Time frame: Up to Day 45
Part 3: Number of Participants With Clinically Significant Electrocardiogram (ECG) Values
Standard resting 12-lead ECG assessments was performed after the participant has rested quietly for at least 5 minutes in supine or semi-recumbent position.
Time frame: Up to Day 26
Part 3: Number Participants With Clinically Significant Vital Signs
Vital signs including systolic and diastolic blood pressure, respiratory rate, heart rate and body temperature were assessed at indicated time points.
Time frame: Up to Day 45
Part 3: Number of Participants With Clinically Significant Physical Findings
Physical examination was performed by a physician or a qualified delegate at the investigating site.
Time frame: Up to Day 26
Part 4: Overall Response Rate (ORR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Overall response rate is defined as the percentage of participants with either a CR or a PR as determined by independent, blinded central review.
Time frame: Up to Day 45
Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs
An adverse event is any untoward medical occurrence or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention.
Time frame: Up to Day 45
Part 3: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL by the Lugano Classification for Lymphoma
Overall response rate is defined as the percentage of participants with either a complete response (CR) or a partial response (PR) as determined by independent, blinded central review board.
Time frame: Up to Day 45
Part 3: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Overall response rate is defined as the percentage of participants with either a CR or a PR as determined by investigator assessment.
Time frame: Up to Day 45
Part 3: Duration of Tumor Response (DOR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
DOR defined as time from initial documentation of tumor response (CR or PR) to disease progression.
Time frame: Up to Day 45
Part 3: Disease Control Rate (DCR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
DCR defined as percentage of participants who have achieved CR, PR and stable disease.
Time frame: Up to Day 45
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BRCR Medical Center
Plantation, Florida, United States
ASCLEPES Research Centers
Weeki Wachee, Florida, United States
Columbus Regional Research Institute
Columbus, Georgia, United States
University of Illinois, Cancer Center
Chicago, Illinois, United States
Healthcare Research Network III, LLC
Tinley Park, Illinois, United States
...and 31 more locations
Part 3: Cmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of Cmax of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 3: Tmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of tmax of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 3: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 3: t1/2 of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of t1/2 of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 3: Vz of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of Vz of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 3: CL of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of CL of MT-3724 monotherapy
Time frame: Up to Day 45
Part 3: PD of MT-3724 Measured by B-cell Count in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by B-cell count in participants with relapsed of refractory DCBCL using flow cytometry.
Time frame: Up to Day 45
Part 3: PD of MT-3724 Measured by Immunophenotyping in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by immunophenotyping in participants with relapsed of refractory DCBCL using flow cytometry.
Time frame: Up to Day 45
Part 3: PD of MT-3724 Measured by Circulating Immunoglobulins in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by circulating immunoglobulins in participants with relapsed of refractory DCBCL.
Time frame: Up to Day 45
Part 3: Number of Participants With ADA When Treated With MT-3724
Blood samples were planned to be collected to analyze the presence of ADA that bind MT-3724.
Time frame: Up to Day 45
Part 4: DOR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Duration of response was defined as the time from the first occurrence of either complete or partial response to first documented evidence of disease recurrence or progression. Participants without evidence of progression were planned to be censored at time of last disease assessment. Only responders (CR or PR) were planned to be included for this analysis.
Time frame: Up to Day 45
Part 4: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs
An adverse event is any untoward medical occurrence or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention.
Time frame: Up to Day 45
Part 4: Number of Participants With SAEs
A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement or is associated with liver injury and impaired liver function.
Time frame: Up to Day 45
Part 4: Number of Participants With Clinically Significant Laboratory Parameters
Blood samples were planned to be collected for the analysis of laboratory parameters.
Time frame: Up to Day 45
Part 4: Number Participants With Clinically Significant Vital Signs
Vital signs parameters including systolic and diastolic blood pressure, heart rate, respiration rate, body temperature and body weight were planned to be analyzed.
Time frame: Up to Day 45
Part 4: Number of Participants With Clinically Significant ECG Values
Standard resting 12-lead ECG assessments was planned to be performed after the participant has rested quietly for at least 5 minutes in supine or semi-recumbent position.
Time frame: Up to Day 26
Part 4: Number of Participants With Adverse Events Suggestive of Cardiotoxicity
Number of participants with any adverse events leading to cardiotoxicity when treated with MT-3724 was planned to be analyzed.
Time frame: Up to Day 26
Part 4: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Overall response rate was defined as the percentage of participants with either a CR or a PR as determined by investigator assessment.
Time frame: Up to Day 45
Part 4: DCR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
DCR was defined as percentage of participants who has achieved CR, PR and stable disease.
Time frame: Up to Day 45
Part 4: Progression-free Survival (PFS) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Progression-free survival was defined as the time from study enrollment to the earliest date of disease progression or death from any cause.
Time frame: Up to Day 45
Part 4: Overall Survival (OS) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Overall survival was defined as the time from study enrollment to death from any cause.
Time frame: Up to Day 45
Part 4: Cmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of Cmax of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 4: Tmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of Tmax of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 4: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 4: t1/2 of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of t1/2 of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 4: Vz of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of Vz of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 4: CL of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of CL of MT-3724 monotherapy.
Time frame: Up to Day 45
Part 4: PD of MT-3724 Measured by B-cell Count in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by B-cell count in participants with relapsed of refractory DCBCL using flow cytometry.
Time frame: Up to Day 45
Part 4: PD of MT-3724 Measured by Immunophenotyping in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by immunophenotyping in participants with relapsed of refractory DCBCL using flow cytometry.
Time frame: Up to Day 45
Part 4: PD of MT-3724 Measured by Circulating Immunoglobulins in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by circulating immunoglobulins in participants with relapsed of refractory DCBCL.
Time frame: Up to Day 45
Part 4: Number of Participants With ADA When Treated With MT-3724
Blood samples were planned to be collected to analyze the presence of ADA that bind MT-3724.
Time frame: Up to Day 45