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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02361346
Other study ID # MT-3724_NHL_001
Secondary ID
Status Terminated
Phase Phase 1/Phase 2
First received
Last updated
Start date February 2015
Est. completion date March 22, 2021

Study information

Verified date July 2022
Source Molecular Templates, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


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Study Design


Intervention

Drug:
MT-3724 Phase 1
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.
MT-3724 Phase 2
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.

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Sponsors (1)

Lead Sponsor Collaborator
Molecular Templates, Inc.

Countries where clinical trial is conducted

United States,  Belarus,  Canada,  Georgia,  Israel,  Moldova, Republic of,  Poland,  Serbia,  Spain,  Ukraine, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Days 1, 3, 5, 8, 10 and 12
Primary 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. Part 1 and 2 : Days 1, 3 and 12
Primary Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724 Blood samples were collected at indicated timepoints for the determination of tmax. Part 1 and 2: Days 1, 3 and 12
Primary 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. Part 1 and 2: Days 1, 3 and 12
Primary 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. Part 1 and 2: Days 1, 3 and 12
Primary 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. Part 1 and 2: Days 1, 3 and 12
Primary Part 1 and 2: Clearance (CL) of MT-3724 Blood samples were collected at indicated timepoints for the analysis of CL of MT-3724. Part 1 and 2: Days 1, 3 and 12
Primary 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 Part 1 and 2: Cycle 1: Days 8 and 23; Cycle 3: Day1; Cycle 5: Day 1 and Day 120 (end of study)
Primary 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. 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)
Primary 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. Up to Day 45
Primary Part 3: Number of Participants With Clinically Significant Laboratory Parameters Blood samples were collected at indicated timepoints for the analysis of laboratory parameters. Up to Day 45
Primary 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. Up to Day 26
Primary 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. Up to Day 45
Primary 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. Up to Day 26
Primary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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 Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary Part 4: Number of Participants With Clinically Significant Laboratory Parameters Blood samples were planned to be collected for the analysis of laboratory parameters. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 26
Secondary 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. Up to Day 26
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
Secondary 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. Up to Day 45
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