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Safety, PD & Efficacy of MT-3724 for the Treatment of Patients With Relapsed or Refractory DLBCL (MT-3724NHL001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02361346
Recruitment Status : Terminated (Sponsor decision following clinical hold)
First Posted : February 11, 2015
Results First Posted : August 18, 2022
Last Update Posted : August 18, 2022
Sponsor:
Information provided by (Responsible Party):
Molecular Templates, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Non-Hodgkin's B-cell Lymphoma Leukemia, Lymphocytic, Chronic, B-Cell Small Lymphocytic Leukemia Diffuse Large B Cell Lymphoma Blood Cancer Hematological Malignancy Drug: MT-3724 Phase 1 Drug: MT-3724 Phase 2 Phase 1 Phase 2

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety, Pharmacodynamics and Efficacy of MT-3724 for the Treatment of Patients With Relapsed or Refractory DLBCL
Actual Study Start Date : February 2015
Actual Primary Completion Date : March 22, 2021
Actual Study Completion Date : March 22, 2021


Arm Intervention/treatment
Experimental: Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose)
Part 1: MT-3724 5 mcg/kg/dose IV for 6 doses over 12 days, followed by dose escalations (Part 1) until recommended phase 2 dose of MT-3724 is determined
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.

Experimental: Part 1: Cohort 2- 10 mcg/kg/Dose
Part 1: MT-3724 10 mcg/kg/dose IV for 6 doses over 12 days, followed by dose escalations (Part) until recommended phase 2 dose of MT-3724 is determined
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.

Experimental: Part 1: Cohort 3- 20 mcg/kg/Dose
Part 1: MT-3724 20 mcg/kg/dose IV for 6 doses over 12 days, followed by dose escalations (Part 1) until recommended phase 2 dose of MT-3724 is determined
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.

Experimental: Part 1: Cohort 4- 50 mcg/kg/Dose
Part 1: MT-3724 50 mcg/kg/dose IV for 6 doses over 12 days, followed by dose escalations (Part 1) until recommended phase 2 dose of MT-3724 is determined
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.

Experimental: Part 1: Cohort 5- 100 mcg/kg/Dose
Part 1: MT-3724 100 mcg/kg/dose IV for 6 doses over 12 days, followed by dose escalations (Phase 1) until recommended phase 2 dose of MT-3724 is determined
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.

Experimental: Part 1: Cohort 6- 75 mcg/kg/Dose
Part 1b: MT-3724 75 mcg/kg/dose IV for 6 doses over 12 days of 21-Day cycle for up to 4 additional cycles to explore safety, tolerability and tumor response to repeat doses of MT-3724 (subject will continue with dose that was tolerated in the Part 1 portion of the study)
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.

Experimental: Part 2: Cohort 7- MTD Expansion Cohort
Part 2: MT-3724 IV for 6 doses administered within 14 days of 21-Day cycle up to 6 Cycles. If the Subject exhibits stable disease or PR after end of Cycle 6 and investigator determines ratio is favorable, treatment with MT- 3724 may be continued for up to additional 6 cycles.
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.

Drug: 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.

Experimental: Part 3: All MT-3724 Treated Participants
Part 3: MT-3724 IV 50 µg/kg/dose administered on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle. Treatment will continue until death, disease progression, unacceptable toxicity, withdrawal of consent, or another reason for withdrawal, or until study discontinuation
Drug: 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.

Experimental: Part 4: All MT-3724 Treated Participants
Part 4: In this arm, subjects were planned to receive all doses of MT-3724 as IV infusion as confirmed in Part 3.
Drug: 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.




Primary Outcome Measures :
  1. Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724 [ Time Frame: Days 1, 3, 5, 8, 10 and 12 ]
    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

  2. Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274 [ Time Frame: Part 1 and 2 : Days 1, 3 and 12 ]
    Blood samples were collected at indicated timepoints for the determination of Cmax of MT-3274.

  3. Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724 [ Time Frame: Part 1 and 2: Days 1, 3 and 12 ]
    Blood samples were collected at indicated timepoints for the determination of tmax.

  4. 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 [ Time Frame: Part 1 and 2: Days 1, 3 and 12 ]
    Blood samples were collected at indicated timepoints for the determination of AUC (0-4), AUC (0-infinity) and AUClast.

  5. Part 1 and 2: Half Life (t1/2) of MT-3724 [ Time Frame: Part 1 and 2: Days 1, 3 and 12 ]
    Blood samples were collected at indicated timepoints for the analysis of t1/2 of MT-3724.

  6. Part 1 and 2: Volume of Distribution (Vz) of MT-3724 [ Time Frame: Part 1 and 2: Days 1, 3 and 12 ]
    Blood samples were collected at indicated timepoints for the analysis of Vz of MT-3724.

  7. Part 1 and 2: Clearance (CL) of MT-3724 [ Time Frame: Part 1 and 2: Days 1, 3 and 12 ]
    Blood samples were collected at indicated timepoints for the analysis of CL of MT-3724.

  8. Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes [ 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) ]
    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

  9. Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed [ 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) ]
    Blood samples were collected to analyze the presence of ADA that bind MT-3724. Number of participants with positive ADA confirmed has been presented.

  10. Part 3: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs [ Time Frame: Up to Day 45 ]
    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.

  11. Part 3: Number of Participants With Clinically Significant Laboratory Parameters [ Time Frame: Up to Day 45 ]
    Blood samples were collected at indicated timepoints for the analysis of laboratory parameters.

  12. Part 3: Number of Participants With Clinically Significant Electrocardiogram (ECG) Values [ Time Frame: Up to Day 26 ]
    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.

  13. Part 3: Number Participants With Clinically Significant Vital Signs [ Time Frame: Up to Day 45 ]
    Vital signs including systolic and diastolic blood pressure, respiratory rate, heart rate and body temperature were assessed at indicated time points.

  14. Part 3: Number of Participants With Clinically Significant Physical Findings [ Time Frame: Up to Day 26 ]
    Physical examination was performed by a physician or a qualified delegate at the investigating site.

  15. Part 4: Overall Response Rate (ORR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Overall response rate is defined as the percentage of participants with either a CR or a PR as determined by independent, blinded central review.


Secondary Outcome Measures :
  1. Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs [ Time Frame: Up to Day 45 ]
    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.

  2. Part 3: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL by the Lugano Classification for Lymphoma [ Time Frame: Up to Day 45 ]
    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.

  3. Part 3: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Overall response rate is defined as the percentage of participants with either a CR or a PR as determined by investigator assessment.

  4. Part 3: Duration of Tumor Response (DOR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    DOR defined as time from initial documentation of tumor response (CR or PR) to disease progression.

  5. Part 3: Disease Control Rate (DCR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    DCR defined as percentage of participants who have achieved CR, PR and stable disease.

  6. Part 3: Cmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected at indicated timepoints for the analysis of Cmax of MT-3724 monotherapy.

  7. Part 3: Tmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected at indicated timepoints for the analysis of tmax of MT-3724 monotherapy.

  8. Part 3: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    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.

  9. Part 3: t1/2 of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected at indicated timepoints for the analysis of t1/2 of MT-3724 monotherapy.

  10. Part 3: Vz of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected at indicated timepoints for the analysis of Vz of MT-3724 monotherapy.

  11. Part 3: CL of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected at indicated timepoints for the analysis of CL of MT-3724 monotherapy

  12. Part 3: PD of MT-3724 Measured by B-cell Count in Participants With Relapsed or Refractory DCBCL [ Time Frame: Up to Day 45 ]
    Pharmacodynamics of MT-3724 was planned to be measured by B-cell count in participants with relapsed of refractory DCBCL using flow cytometry.

  13. Part 3: PD of MT-3724 Measured by Immunophenotyping in Participants With Relapsed or Refractory DCBCL [ Time Frame: Up to Day 45 ]
    Pharmacodynamics of MT-3724 was planned to be measured by immunophenotyping in participants with relapsed of refractory DCBCL using flow cytometry.

  14. Part 3: PD of MT-3724 Measured by Circulating Immunoglobulins in Participants With Relapsed or Refractory DCBCL [ Time Frame: Up to Day 45 ]
    Pharmacodynamics of MT-3724 was planned to be measured by circulating immunoglobulins in participants with relapsed of refractory DCBCL.

  15. Part 3: Number of Participants With ADA When Treated With MT-3724 [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected to analyze the presence of ADA that bind MT-3724.

  16. Part 4: DOR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    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.

  17. Part 4: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs [ Time Frame: Up to Day 45 ]
    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.

  18. Part 4: Number of Participants With SAEs [ Time Frame: Up to Day 45 ]
    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.

  19. Part 4: Number of Participants With Clinically Significant Laboratory Parameters [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected for the analysis of laboratory parameters.

  20. Part 4: Number Participants With Clinically Significant Vital Signs [ Time Frame: Up to Day 45 ]
    Vital signs parameters including systolic and diastolic blood pressure, heart rate, respiration rate, body temperature and body weight were planned to be analyzed.

  21. Part 4: Number of Participants With Clinically Significant ECG Values [ Time Frame: Up to Day 26 ]
    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.

  22. Part 4: Number of Participants With Adverse Events Suggestive of Cardiotoxicity [ Time Frame: Up to Day 26 ]
    Number of participants with any adverse events leading to cardiotoxicity when treated with MT-3724 was planned to be analyzed.

  23. Part 4: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Overall response rate was defined as the percentage of participants with either a CR or a PR as determined by investigator assessment.

  24. Part 4: DCR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    DCR was defined as percentage of participants who has achieved CR, PR and stable disease.

  25. Part 4: Progression-free Survival (PFS) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Progression-free survival was defined as the time from study enrollment to the earliest date of disease progression or death from any cause.

  26. Part 4: Overall Survival (OS) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Overall survival was defined as the time from study enrollment to death from any cause.

  27. Part 4: Cmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected at indicated timepoints for the analysis of Cmax of MT-3724 monotherapy.

  28. Part 4: Tmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected at indicated timepoints for the analysis of Tmax of MT-3724 monotherapy.

  29. Part 4: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    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.

  30. Part 4: t1/2 of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected at indicated timepoints for the analysis of t1/2 of MT-3724 monotherapy.

  31. Part 4: Vz of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected at indicated timepoints for the analysis of Vz of MT-3724 monotherapy.

  32. Part 4: CL of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected at indicated timepoints for the analysis of CL of MT-3724 monotherapy.

  33. Part 4: PD of MT-3724 Measured by B-cell Count in Participants With Relapsed or Refractory DCBCL [ Time Frame: Up to Day 45 ]
    Pharmacodynamics of MT-3724 was planned to be measured by B-cell count in participants with relapsed of refractory DCBCL using flow cytometry.

  34. Part 4: PD of MT-3724 Measured by Immunophenotyping in Participants With Relapsed or Refractory DCBCL [ Time Frame: Up to Day 45 ]
    Pharmacodynamics of MT-3724 was planned to be measured by immunophenotyping in participants with relapsed of refractory DCBCL using flow cytometry.

  35. Part 4: PD of MT-3724 Measured by Circulating Immunoglobulins in Participants With Relapsed or Refractory DCBCL [ Time Frame: Up to Day 45 ]
    Pharmacodynamics of MT-3724 was planned to be measured by circulating immunoglobulins in participants with relapsed of refractory DCBCL.

  36. Part 4: Number of Participants With ADA When Treated With MT-3724 [ Time Frame: Up to Day 45 ]
    Blood samples were planned to be collected to analyze the presence of ADA that bind MT-3724.



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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must be informed about the study and fully consent to participation as demonstrated by signing the written ICF before any screening procedure.
  • Male and female participants >= 18 years of age at the time of informed consent.
  • Participants must have relapsed or refractory Diffuse large B cell lymphoma (DLBCL) according to the Revised European American Lymphoma/World Health Organization classification. Participants must have proof of cluster of differentiation 20 plus (CD20+) DLBCL, based on either:

    • a. historical biopsies (obtained with diagnosis of relapsed or refractory disease), or
    • b. fresh biopsies
    • c. bone marrow biopsy, excisional lymph node biopsy, and core biopsy of any involved organ are all acceptable methods; Fine Needle Aspirate is not acceptable.
  • Participants must have received at least 2 standard of care (SoC) regimens (including anti-CD20 antibody therapy) appropriate for DLBCL treatment.

    • a. Participants whose prior therapy includes chimeric antigen receptor T-cell (CAR-T-cell) therapy are eligible.
    • b. Participants who underwent stem cell transplant (SCT) > 100 days for autologous SCT or > 180 days for allogeneic SCT before study drug administration.
    • c. Participants who have been ineligible for SoC DLBCL treatments may be eligible at the investigator's discretion, upon sponsor approval.
  • Participants must have at least 1 bi-dimensional tumor lesion at screening that is measurable by computerized tomography (CT) and/or magnetic resonance imaging (MRI) according to the Lugano criteria. Bi-dimensionally measurable tumor lesion by CT and/or MRI is defined as longest diameter of > 1.5 centimeters (cm) for lymph nodes and > 1.0 cm for extranodal disease.
  • Participants must have life expectancy of > 3 months from the start of treatment.
  • Participants must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Participants must have met ALL the following laboratory criteria:

    • a. absolute neutrophil count (ANC) >= 1.0 × 10^9 cells per liter with no myeloid growth factors (granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor preparations) administered within 2 weeks of Cycle 1 Day 1.
    • b. platelet count >= 50 × 10^9 cells per liter with no Thrombopoietin-receptor agonists agents or platelet transfusions given within 2 weeks of Cycle 1 Day 1.
    • c. hemoglobin >= 8.0 grams per deciliter (g/dL) with no erythropoietin stimulating agents or peripheral red blood cell (PRBC) transfusions within 2 weeks of Cycle 1 Day 1
    • d. creatinine clearance (CLcr) to be >= 50 milliliter per minute (ml/min) either measured or estimated using the Cockcroft-Gault formula.
    • e. total bilirubin (or direct bilirubin for patients with Gilbert's disease < 1.5 × upper limit of normal (ULN)
    • f. alanine transaminase (ALT) ≤ 3.0 × ULN (or <= 5.0 x ULN if liver involvement).
    • g. aspartate aminotransferase (AST) <= 3.0 × ULN (or <= 5.0 x ULN if liver involvement).
    • h. international normalized ratio (INR) or prothrombin time (PT) <= 1.5 x ULN (unless on therapeutic anticoagulants).
    • i. Activated partial thromboplastin time <= 1.5 x ULN (unless on therapeutic anticoagulants).
  • Have adequate serum albumin, as determined by: a. albumin >= 3.0 g/dL.
  • QT interval correction for heart rate using Fridericia's formula (QTcF) <= 480 milliseconds determined as the average of 3 QTcF values from the triplicate electrocardiogram (ECG) obtained at screening.
  • Women of reproductive potential must have a negative highly sensitive pregnancy test within 72 hours before the start of treatment. Women who are postmenopausal or permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy) may be considered as not of reproductive potential.
  • Participants of reproductive potential must agree either to abstain continuously from heterosexual intercourse or to use a highly effective birth control method from signing the informed consent until the short term follow-up (STFU) visit for females and until 90 days after the last dose of MT-3724 for males.
  • Participants must be able to comply with all study-related procedures and medication use.

Exclusion Criteria

Prior or Current Therapies

  • Received any amount of anti-CD20 monoclonal antibodies (mAbs) within the following periods before the start of treatment:

    • a. Rituximab (Rituxan®/MabThera® or rituximab biosimilar): within 84 days (12 weeks); if a participant has received rituximab within 37 weeks before the start of treatment, then serum rituximab level must be negative (< 500 nanograms per milliliter [ng/mL]) at screening.
    • b. Obinutuzumab (Gazyva®/Gazyvaro®): 184 days c. Ofatumumab (Arzerra®): 88 days d. Any other anti-CD20 agents (eg, investigational agents), the washout period is 5 half-lives. The investigator must contact the medical monitor to discuss the most Compound: MT-3724 appropriate washout for non-approved CD20-targeting agents, where the half-life (t1/2) is not known.
  • Received approved or investigational treatment for DLBCL within 4 weeks before the start of treatment. For small molecules (MW < 0.9 kilodaltons [kDa]), the washout is 5 half-lives or at least 2 weeks. Radioimmunoconjugates are excluded within 12 weeks before the start of treatment.
  • Received radiation therapy to tumor lesions that would serve as target lesions (measurable disease) within 4 weeks before the start of treatment, unless the lesion exhibited objective progression between radiation therapy and screening according to the Lugano Classification

    o a. Palliative radiation therapy to non-target lesions may be permitted at the investigator's discretion after consultation with the medical monitor and sponsor.

  • Require the use of systemic immune modulators during study treatment:

    • a. Systemic immune modulators include, but are not limited to, systemic corticosteroids at doses > 20 milligrams per day (mg/day) of prednisone equivalent, cyclosporine and tacrolimus.
    • b. The use of non-steroidal anti-inflammatory drugs (NSAIDS) is permitted.
  • Received any live vaccines within 4 weeks before the start of treatment.
  • Prior treatment with MT-3724.

Medical History

  • Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1 toxicity (due to prior anticancer therapy) before the start of treatment, except for hair loss and those Grade 2 toxicities listed as permitted in other eligibility criteria.
  • Current evidence of significant (CTCAE Grade ≥ 2) infection or wound within 4 weeks before the start of treatment. a. Participants with Grade 2 infection that has stabilized or improved with oral anti-infectives before the start of treatment may be eligible at the sponsor's discretion.
  • Known or suspected hypersensitivity to the study drug or excipients contained in the study drug formulation.
  • Current evidence of hypersensitivity or other underlying illness requiring systemic corticosteroids at doses > 20 mg/day prednisone equivalent.
  • Current evidence of uncontrolled human immunodeficiency syndrome (HIV), hepatitis B virus (HBV) or /hepatitis C virus (HCV) at screening. Serology testing is not required if seronegativity is documented in the medical history, and if there are no clinical signs suggestive of HIV or hepatitis infections, or suspected exposure. The following exceptions apply for participants with positive viral serology:

    • a. Participants with HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts >= 350 cells per milliliter may be enrolled, but must be taking appropriate opportunistic infection prophylaxis, if clinically relevant.
    • b. Participants with positive HBV serology are eligible if they have an undetectable viral load and the participant will receive antiviral prophylaxis for potential HBV reactivation per institutional guidelines.
    • c. Participants with positive HCV serology are eligible if quantitative polymerase chain reaction (PCR) for plasma HCV ribonucleic acid (RNA) is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.
  • Current evidence of incomplete recovery from surgery or radiotherapy before start of treatment, or planned surgery or radiotherapy from the start of treatment until the end of treatment (EoT) visit, except minor elective surgery deemed acceptable by the investigator or palliative radiation therapy to non-target lesions.
  • History of cardiovascular, renal, hepatic or any other disease within 3 months before the start of treatment that in the investigator's opinion, may increase the risks associated with study participation or require treatments that may interfere with the conduct of the study or the interpretation of study results.
  • History or current evidence of neoplastic disease that is histologically distinct from NHL, except cervical carcinoma in situ, superficial noninvasive bladder tumors, curatively treated Stage I-II non-melanoma skin cancer. Participants with prior, curatively treated cancer > 2 years ago before the start of treatment can be enrolled.
  • Current evidence of new or growing brain or spinal metastases during screening. Participants with known brain or spinal metastases may be eligible if they:

    • a. Had radiotherapy or another appropriate therapy for the brain or spinal metastases; concurrent prophylactic treatment is allowed
    • b. Neurologic symptoms must be stable and no worse than Grade 2
    • c. Have evidence of stable brain or spinal disease on CT or MRI scan obtained within 4 weeks before signing the informed consent and compared with prior imaging results
    • d. Do not require steroid therapy (or, if applicable, have been stable on dose of no more than prednisone 20 mg/day or equivalent by C1D1)
  • Women who are pregnant or breastfeeding.
  • History of non-adherence to the schedule of procedures or medication use. 18. Current evidence of Graft vs Host Disease
  • History or current evidence of significant cardiovascular disease including, but not limited to, the following conditions:

    • a. Unstable angina (symptoms of angina at rest) or new-onset angina within 3 months before the start of treatment.
    • b. Arterial thrombosis or pulmonary embolism within 3 months before the start of treatment.
    • c. Myocardial infarction or stroke within 3 months before the start of treatment.
    • d. Pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade >= 2), non-malignant pleural effusion (CTCAE Grade ≥ 2) or malignant pleural effusion (CTCAE Grade >= 3) within 3 months before the start of treatment with MT-3724.
    • e. Congestive heart failure (New York Heart Association [NYHA] Class III or IV) at screening or left ventricular ejection fraction (LVEF) <= 45 percent (%), assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 1 month before starting study treatment (inclusion of participants with LVEF between 40% to 45% should be discussed with the medical monitor and approved by the sponsor). (ECHO or MUGA performed within 6 months before screening and at least 28 days after the last cancer therapy is acceptable provided the participant has not received any potentially cardiotoxic agents since then).
    • f. Cardiac arrhythmia requiring anti-arrhythmic therapy at screening. Participants receiving digoxin, calcium channel blockers, or beta-adrenergic blockers are eligible at the investigator's discretion after consultation with medical monitor and sponsor if the dose has been stable for >= 2 weeks before the start of treatment with MT-3724. Participants with sinus arrhythmia and infrequent premature ventricular contractions are eligible at the investigator's discretion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02361346


Locations
Show Show 41 study locations
Sponsors and Collaborators
Molecular Templates, Inc.
  Study Documents (Full-Text)

Documents provided by Molecular Templates, Inc.:
Study Protocol  [PDF] February 12, 2021
Statistical Analysis Plan  [PDF] August 15, 2018

Layout table for additonal information
Responsible Party: Molecular Templates, Inc.
ClinicalTrials.gov Identifier: NCT02361346    
Other Study ID Numbers: MT-3724_NHL_001
First Posted: February 11, 2015    Key Record Dates
Results First Posted: August 18, 2022
Last Update Posted: August 18, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Molecular Templates, Inc.:
CD20
immunotoxin
NHL
non-Hodgkin's lymphoma
lymphoma
cancer
antibodies
immunotherapy
safety
pharmacokinetics
maximum tolerated dose
MT-3724
relapsed
refractory
leukemia
CLL
SLL
DLBCL
efficacy
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Leukemia, Lymphoid
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Hematologic Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Neoplasms by Site
Hematologic Diseases
Leukemia, B-Cell