Molecular Templates, Inc.

MT-3724 for Relapsed or Refractory DLBCL

Trial Summary

Official Title

Safety, Pharmacodynamics and Efficacy of MT-3724 for the Treatment of Patients With Relapsed or Refractory DLBCL

Status

Active, not recruiting

Condition

Non-Hodgkin's B-cell Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Small Lymphocytic Leukemia, Diffuse Large B Cell Lymphoma, Blood Cancer, Hematological Malignancy

Actual Start Date

February 2015

Estimated Primary Completion Date

June 2022

About the Trial

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

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.

Detailed Info

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.

Study Phase

Phase 1/Phase 2

Estimated Enrollment

130

Estimated Primary Completion Date

June 2022

Study Type

Interventional

Interventions

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

Sponsor

Molecular Templates, Inc.

Inclusion Criteria

Gender

Male & Female

Age

18 Years and older

  • Men or women, age 18 years or older

Part 1:

• Histology based upon bone marrow biopsies and/or fine needle aspirates as the sole means of diagnosis are not acceptable. All subtypes of B-cell NHL may be considered for the MT-3724 dose escalation. Presence of lymphadenopathy and/or splenomegaly with histopathological evaluation of a lymph node biopsy consistent with CLL.

Part 2:

  1. Diffuse large B cell lymphoma (DLBCL). Histology based upon bone marrow biopsies and/or fine needle aspirates as the sole means of diagnosis are not acceptable.
  2. Subjects must have received at least one anti-CD20 antibody containing regimen that resulted in initial measurable response (partial or complete remission), followed by relapse/ recurrence.
  3. Life expectancy > 3 months.
  4. Eastern Cooperative Oncology Group (ECOG) performance score of ≤2.
  5. All lymphoma subjects are required to have measurable disease
  6. Patients must be at least 28 days past their last course of lymphoma
  7. Received any amount of anti-CD20 MAb therapy within the following periods before the start of treatment
  8. Received any amount of anti-CD20 MAb within the following periods before the start of treatment:

    1. Rituximab (Rituxan®): if a subject had received any amount of rituximab within 365 days of planned dose day 1 then a serum rituximab level must be negative (<500 ng/ml) at the screening period
    2. Obinutuzumab (Gazyva®): 184 days
    3. Ofatumumab (Arzerra®): 88 days
    4. ibritumomab tiuxetan (Zevalin®): 10 days
  9. Adequate kidney function, assessed by the estimated glomerular filtration rate (eGFR) ≥60 mL/min
  10. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to initiating dosing. Male and female subjects with reproductive potential must agree to use acceptable contraceptive methods until the end of study visit.
  11. Patients with known central nervous system metastases may be enrolled if they have received radiotherapy, do not require chronic steroid therapy, have had computed tomography or magnetic resonance imaging of the brain within 1 month of study entry that shows stable disease and they have no neurological symptoms other than low grade neuropathy.

Part 3:

  1. Subjects must have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) according to the Revised European American Lymphoma/World Health Organization (REAL/WHO) classification.
  2. Subjects must have received at least 2 standard of care regimens for NHL treatment.
  3. Subjects must have at least one tumor lesion at screening
  4. Subjects must have life expectancy of >3 months from the start of treatment.
  5. Subjects must have ECOG performance status of 0-2.
  6. Adequate kidney function
  7. QTcF (Fridericia) ≤480 ms determined as the average of three QTcF values from the triplicate ECG obtained at screening.
  8. LVEF ≥45% by MUGA or echocardiogram obtained at screening.
  9. Female patients of childbearing potential must not be pregnant.. Male and female subjects with reproductive potential must agree to use acceptable contraceptive methods until the end of study visit.
  10. Subject must be able to comply with all study-related procedures and medication use.

Exclusion Criteria

  1. History of another cancer other than basal cell carcinoma or cervical intraepithelial neoplasia (CIN; i.e., cervical cancer in situ).
  2. Potential subjects cannot have experienced a significant (CTCAE Grade 3 or 4 with or without neutropenia) infection within 2 weeks of the first dose of MT-3724.
  3. Ongoing use of any approved or investigational antineoplastic therapies
  4. Systemic corticosteroid therapy at a prednisone dose > 20mg/day (or equivalent) within 14 days prior to study enrollment
  5. Potential subjects with pre-existing AEs at screening that are severe or life threatening by CTCAE, v. 4.03 should not be enrolled.
  6. Patients with uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to start of study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis may not be enrolled.
  7. Patients with a known history of drug abuse or any chronic neurologic, psychiatric, endocrine, metabolic, immunologic, hepatic or renal disease (including a history of hemolytic uremic syndrome) that in the opinion of the Investigator would adversely affect study participation.
  8. Potential subjects must not have received any vaccines for 28 days prior to administration of their first dose of MT-3724 and should not receive any vaccine during the study or within 28 days after their last dose of MT-3724. The single exception to this exclusion is for the annual influenza (flu) vaccine which can be given up to 14 days prior to first dose.
  9. History of hypersensitivity to study drug or to compounds of a similar class, or whose past history suggests an increased potential for an adverse hypersensitivity reaction to MT-3724 should not be enrolled.
  10. Patients with known active Hepatitis A or C, HIV or a present history of Hepatitis B
  11. Potential subjects who have undergone allogeneic hematopoietic stem cell transplantation.
  12. Women who are pregnant or breastfeeding.
  13. Potential subjects who have had major surgery within 6 weeks prior to the first dose of study drug or have major surgery planned during the first 12 weeks post MT 3724 exposure
  1. Received any amount of anti-CD20 MAb within the following periods before the start of treatment:
    1. Rituximab (Rituxan®/MabThera® or rituximab biosimilar): if administered within 12 to 37 weeks before the start of treatment, then serum rituximab level must be assessed during the screening and confirmed as negative (<500 ng/mL)
    2. Obinutuzumab (Gazyva®/Gazyvaro®): 184 days.
    3. Ofatumumab (Arzerra®): 88 days.
  2. Received approved or investigational treatment for NHL (except anti-CD20 MAb and radioimmunoconjugates) within 4 weeks before the start of treatment. Radioimmunoconjugates are excluded within 12 weeks before the start of treatment.
  3. Received radiation therapy to target lesions ) within 4 weeks before the start of treatment, unless the lesions exhibited objective progression between radiation therapy and screeninga. Palliative radiation therapy to non-target lesions within 4 weeks before the start of treatment may be permitted at the investigator's discretion.
  4. Received systemic immunosuppressive agents (except prescribed corticosteroids at doses ≤20 mg/day prednisone equivalent) within 2 weeks before the start of treatment
  5. Received any vaccines except injectable flu (inactivated or recombinant) vaccine within 4 weeks before the start of treatment, or likely to require any vaccines except injectable flu vaccine at any time from the start of treatment until 28 days after the last dose of MT-3724.
  6. Received allogeneic stem cell transplant.
  7. Current evidence of CTCAE Grade ≥2 (significant) 1 toxicity before the start of treatment, except for hair loss and those significant toxicities permitted in other eligibility criteria. Subjects with significant permitted in other eligibility criteria. Subjects with significant
  8. History or current evidence of significant infection, systemic infection or wound within 2 weeks before the start of treatment.a. Subjects with significant infection that has stabilized or improved with oral antibiotics before the start of treatment may be eligible at the investigator's discretion.
  9. Known or suspected hypersensitivity to the study drug or excipients contained in the study drug formulation.
  10. Current evidence of hypersensitivity or other underlying illness requiring systemic corticosteroids at doses >20 mg/day prednisone equivalent
  11. Patients with known active Hepatitis C, HIV or a present history of Hepatitis B
  12. Current evidence of incomplete recovery from surgery or radiotherapy at screening, or planned surgery or radiotherapy from the start of treatment until the short term follow-up visit, except minor elective surgery or palliative radiation therapy to non-target lesions deemed acceptable by the investigator.
  13. History of cardiovascular, renal, hepatic or any other disease within ≤3 months before the start of treatment
  14. History of another primary malignancy within the past 3 years (except for ductal breast cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and cervical carcinoma in situ) that required systemic drug therapy or radiotherapy.
  15. Current evidence of new or growing brain or spinal metastases during screening.
  16. Women who are pregnant or breastfeeding.
  17. History of non-adherence to the schedule of procedures or medication use

Location

The following cities have clinical trial sites. Please check back often as locations will be updated.

University of Arizona
Tucson, Arizona 85724
United States

Innovative Clinical Research Institute, LLC
Whittier, California 90602
United States

21st Century Oncology - Jacksonville
Jacksonville, Florida 32204
United States

Orlando Health, Inc.
Orlando, Florida 32806
United States

Orlando Health, Inc.
Orlando, Florida
United States

BRCR Medical Center
Plantation, Florida 33322
United States

ASCLEPES Research Centers
Weeki Wachee, Florida 34607
United States

Columbus Regional Research Institute
Columbus, Georgia 31904
United States

University of Illinois, Cancer Center
Chicago, Illinois 60612
United States

Healthcare Research Network III, LLC
Tinley Park, Illinois
United States

Carle Foundation Hospital
Urbana, Illinois
United States

Norton Healthcare, Inc
Louisville, Kentucky
United States

New York University Langone Medical Center
New York, New York 10016
United States

Memorial Sloan-Kettering Cancer Center
New York, New York 10065
United States

University of North Carolina
Chapel Hill, North Carolina 27599
United States

MD Anderson Cancer Center
Houston, Texas 77030
United States

UT Health San Antonio Cancer
San Antonio, Texas 78229
United States

Grodno University Hospital
Grodno,
Belarus

Minsk City Clinical Oncology Center
Minsk, 220013
Belarus

Cross Cancer Institute
Edmonton, Alberta
Canada

Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario K7L 2V7
Canada

Princess Margaret Cancer Centre
Toronto, Ontario M5G 2M9
Canada

Montreal Oncology Research
Quebec, H1M 1B1
Canada

LLC ARENSIA Exploratory Medicine
Tbilisi, 0112
Georgia

Rabin Medical Center, Davidoff Cancer Center, Hemato-Oncology Institute
Petah-Tikva, 49100
Israel

Chaim Sheba Medical Center, Department of Hematology
Ramat Gan,
Israel

The Tel Aviv Sourasky Medical Center, Department of Hematology and Bone Marrow Transplantation
Tel-Aviv,
Israel

ARENSIA Exploratory Medicine,
Chisinau, MD-2025
Moldova, Republic of

Maria Sklodowska-Curie National Institute of Oncology - National Research Institute
Gliwice,
Poland

University Hospital in Krakow, Teaching Unit of the Hematology Department
Kraków,
Poland

Frederic Chopin Provincial Teaching Hospital, Teaching Department of Hematology
Rzeszów, 35-055
Poland

Our Doctor Clinical Trials Center
Torun,
Poland

Institute of Hematology and Transfusion Medicine, Department of Hematology
Warsaw,
Poland

Jan Mikulicz Radecki University Hospital in Wroclaw, Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation
Wroclaw, 50-367
Poland

Clinical Center Kragujevac, Clinic of Hematology
Kragujevac,
Serbia

Clinical Center of Vojvodina, Clinic of Hematology
Novi Sad,
Serbia

Catalan Institute of Oncology (ICO) - Hospital Duran i Reynals, Department of Clinical Hematology
Barcelona,
Spain

University Hospital Vall d'Hebron (HUVH), Department of Hematology
Barcelona,
Spain

Hospital Universitario QuironSalud Madrid
Madrid, 28223
Spain

University Hospital Virgen del Rocio (HUVR), Department of Hematology
Seville,
Spain

Medical Center of Limited Liability Company "Medical Centre Named by Academician Yurii Spizhenko
Kyiv, 08112
Ukraine

Enrollment

For more information on enrollment in our current clinical trials, please visit clinicaltrials.gov for location information.

About Diffuse Large B-Cell Non-Hodgkin's Lymphoma

About Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a type of cancer that starts in white blood cells called lymphocytes. There are two types of lymphoma: Hodgkin's and non-Hodgkin's, and the each behave, grow, and respond to treatment differently. There are several types of DLBCL, with the most common being non-Hodgkin's lymphoma.

Frequently Asked Questions

A Clinical Trial is a type of research study that examines how well a potential therapy works in humans.
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 clinical trial has certain criteria that a person has to meet to determine if they can participate. After you have discussed the trial with your doctor, specific tests will be done to see if you qualify for this study.
Molecular Templates is sponsoring this clinical trial.
There will be a total of 130 patients enrolled in this clinical trial.
Have your physician complete the contact form.

The safety and efficacy of the investigational use of this product has not been determined. There is no guarantee that the investigational use listed will be filed with and/or approved for marketing by a regulatory agency.