We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 3 for:    molecular templates [Lead]

PK, PD, Safety, Tolerability of Multiple Dose Regimens of MT-3724 for the Treatment of Patients With Relapsed Non-Hodgkin's B-Cell Lymphoma and B-Cell Chronic Lymphocytic Leukemia (MT-3724NHL001)

This study is currently recruiting participants.
Verified December 2017 by Molecular Templates, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02361346
First Posted: February 11, 2015
Last Update Posted: December 11, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Molecular Templates, Inc.
  Purpose
This Phase I, multiple ascending dose study will seek to enroll subjects with progressive B cell non-Hodgkin's lymphoma with measurable disease (lesion > 1.5 cm) (including SLL) OR relapsed/refractory B-cell CLL who have received standard treatment with at least one anti-CD20 antibody (e.g.; rituximab, ofatumumab)) containing front-line regimen that resulted in initial response, followed by relapse/recurrence and who are not eligible for any further approved biologic therapy, chemotherapy and/or autologous stem transplantation and/or refuse alternative approved therapies and/or are unlikely to achieve clinical benefit from any therapy of higher priority by Investigator assessment.

Condition Intervention Phase
Non-Hodgkin's B-cell Lymphoma Leukemia, Lymphocytic, Chronic, B-Cell Small Lymphocytic Leukemia Drug: MT-3724 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Multiple Dose Regimens of MT-3724 for the Treatment of Patients With Relapsed Non-Hodgkin's B-Cell Lymphoma and B-Cell Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Molecular Templates, Inc.:

Primary Outcome Measures:
  • Tolerability as measured by number of subjects with dose limiting toxicities [ Time Frame: 28 days ]
    Evaluation of tolerability of MT-3724 measured by number of subjects with dose limiting toxicities (DLTs)

  • Safety as measured by number of subjects with Adverse Events using CTCAE [ Time Frame: 28 days and then every 6 months for up to 24 months following first dose if subject does not continue into Phase Ib ]
    Safety measured by number of subjects with Adverse Events using CTCAE Version 4.03

  • Tolerability as measured by adverse events using CTCAE and clinical laboratory parameters [ Time Frame: 2-3 weeks following last dose and then every 6 months for up to 24 months following first dose ]
    Evaluation of tolerability of MT-3724 given for up to 4 additional cycles measured by number, nature and severity of Adverse Events using CTCAE Version 4.03


Secondary Outcome Measures:
  • PK as measured by concentrations of free MT-3724 (Cmax, AUC, tmax, Cinf) [ Time Frame: Days 1, 5, 8, 12, 23, and 28 ]
    Evaluation of the pharmacokinetic profile of MT-3724

  • PD as measured by clinical symptoms, tumor response, immunogenicity [ Time Frame: Days 1, 5, 8, 12, 23, and 28 ]
    Evaluation of the pharmacodynamic profile of MT-3724

  • Tumor Response as measured by PET or CT scan [ Time Frame: Days 43 and 86 ]
    Evaluation of tumor response using International Working Group Response Criteria


Estimated Enrollment: 60
Study Start Date: February 2015
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MT-3724 Phase 1 5 mcg/kg/dose
Phase 1: MT-3724 5 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks), followed by dose escalations (Phase 1) until recommended phase 2 dose of MT-3724 is determined
Drug: MT-3724
Intravenous dosing M-W-F X 2 weeks; MT-3724 infusion over 2 hours on each dosing day over 4 week initial cycle and then 3 week repeat cycles for up to 5 total cycles.
Experimental: MT-3724 Phase 1b
Phase 1b: MT-3724 IV for 6 doses over 12 days 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 Phase 1 portion of the study)
Drug: MT-3724
Intravenous dosing M-W-F X 2 weeks; MT-3724 infusion over 2 hours on each dosing day over 4 week initial cycle and then 3 week repeat cycles for up to 5 total cycles.
Experimental: MT-3724 Phase 1 10 mcg/kg/dose
Phase 1: MT-3724 10 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks), followed by dose escalations (Phase 1) until recommended phase 2 dose of MT-3724 is determined
Drug: MT-3724
Intravenous dosing M-W-F X 2 weeks; MT-3724 infusion over 2 hours on each dosing day over 4 week initial cycle and then 3 week repeat cycles for up to 5 total cycles.
Experimental: MT-3724 Phase 1 20 mcg/kg/dose
Phase 1: MT-3724 20 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks), followed by dose escalations (Phase 1) until recommended phase 2 dose of MT-3724 is determined
Drug: MT-3724
Intravenous dosing M-W-F X 2 weeks; MT-3724 infusion over 2 hours on each dosing day over 4 week initial cycle and then 3 week repeat cycles for up to 5 total cycles.
Experimental: MT-3724 Phase 1 50 mcg/kg/dose
Phase 1: MT-3724 50 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks), followed by dose escalations (Phase 1) until recommended phase 2 dose of MT-3724 is determined
Drug: MT-3724
Intravenous dosing M-W-F X 2 weeks; MT-3724 infusion over 2 hours on each dosing day over 4 week initial cycle and then 3 week repeat cycles for up to 5 total cycles.
Experimental: MT-3724 Phase 1 100 mcg/kg/dose
Phase 1: MT-3724 100 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks), followed by dose escalations (Phase 1) until recommended phase 2 dose of MT-3724 is determined
Drug: MT-3724
Intravenous dosing M-W-F X 2 weeks; MT-3724 infusion over 2 hours on each dosing day over 4 week initial cycle and then 3 week repeat cycles for up to 5 total cycles.
Experimental: MT-3724 Phase 1 75 mcg/kg/dose
Phase 1b: MT-3724 IV for 6 doses over 12 days 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 Phase 1 portion of the study)
Drug: MT-3724
Intravenous dosing M-W-F X 2 weeks; MT-3724 infusion over 2 hours on each dosing day over 4 week initial cycle and then 3 week repeat cycles for up to 5 total cycles.

Detailed Description:

This is a two-part study intended to provide investigators and sponsor with the following information regarding the investigational new drug MT-3724:

Part 1[COMPLETED]: in patients with relapsed/refractory non-Hodgkin's B cell lymphoma (including SLL) OR relapsed/refractory B-cell CLL

  1. The maximum dose of a single course of MT-3724 given as intravenous (IV) infusions on Days 1, 3, 5, 8, 10 and 12 at which there are negligible side effects and/or at which maximum serum levels and/or at which maximum effect on blood lymphocytes are observed. Six dose levels will be investigated.
  2. The changes in MT-3724 serum levels and blood lymphocytes over time following IV doses at different points in the study.
  3. The changes and kinds of clinical and laboratory effects and side effects that may occur over repeated courses of MT-3724.
  4. The changes in each subject's immune status and their non-Hodgkin's lymphoma following one or more cycles of 6 infusions.

Part 2: An expansion of the maximum tolerated dose cohort in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL)

  1. Identify the frequency of nature of clinical and laboratory adverse events that may occur over repeated courses of MT-3724 at the maximum tolerated dose.
  2. Define the PK and PD profiles of MT-3724 at the maximum tolerated dose.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men or women, age 18 years or older

Part 1:

  • Histologic diagnosis of B-Cell NHL. Histology based upon bone marrow biopsies and/or fine needle aspirates as the sole means of diagnosis are not acceptable. All patients must have measurable disease. Any tumor mass of at least 1.5 cm is acceptable.
  • Presence of lymphadenopathy and/or splenomegaly with histopathological evaluation of a lymph node biopsy consistent with CLL. Clonality of the circulating B-lymphocytes should be confirmed at screening. Previously confirmed immunohistological diagnosis with a characteristic CD5+/CD20+ B--cell immunophenotype according to WHO criteria. CLL diagnosis requires an absolute peripheral blood monoclonal CD20+/CD5+ B-lymphocyte count ≥ 5000 cells/μL for the duration of at least 3 months.

Part 2:

  • 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.
  • Subject must have the following staging requirements:

    1. CLL (Part 1): Rai Stage III or IV disease, or stage 0-II disease that meets National Cancer Institute Working Group (NCIWG) criteria for active disease requiring therapy that may include either of the following disease-related symptoms:

      • Progressive lymphadenopathy including bulky disease as defined by mass, lymph node or lymph node cluster > 10 cm.
      • Progressive lymphocytosis with > 50% increase over a 2-month period, or anticipated doubling time < 6 months.
    2. NHL (Part 1 and 2): Intermediate or high risk by Ann Arbor Staging with Cotswald Modifications that meets criteria for active disease requiring therapy.
  • History of at least one anti-CD20 antibody containing regimen that resulted in initial measurable response (partial or complete remission), followed by relapse/recurrence.
  • Patients must have received all approved therapies known to provide clinical benefit for their disease subtype and for which they are eligible or must have refused these treatment options prior to consideration for enrolment. In the case of patients who have lymphomas for which high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) is considered a standard curative therapy, eligibility for this study requires that the patient's disease has relapsed after HD-ASCT, that the patient is not eligible for HD-ASCT, or that the patient has refused HD-ASCT.
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of < 2.
  • Patients must be at least 28 days past their last course of lymphoma or CLL treatment, at least 84 days past their last course of rituximab treatment. Patients with pre-existing severe or life threatening side effects/conditions from prior therapy or due to other diseases may not be enrolled
  • Part 2: Subjects who have received any amount of rituximab within 256 days (37 weeks; 8 half-lives) of planned dose day 1 must have a serum rituximab level of <500 ng/mg documented by the study's reference laboratory prior to the initiation of dosing. Potential subjects who have received any other anti CD20 MAb therapy (obinutuzumab, ofatumumab, or ibritumomab tiuxetan) must be at least 8 half-lives past their last dose prior to initiation of study drug dosing. Washout periods for these drugs are as follows:

    1. obinutuzumab (terminal half-life in NHL = 36.8 days); required washout = 184 days (26 weeks)
    2. ofatumumab (terminal half-life in CLL = 17.6 days); required washout = 88 days (13 weeks)
    3. ibritumomab tiuxetan (biologic half-life in NHL = 1.9 days [based upon measurement of radioactivity from administered [111In]-ibritumomab tiuxetan]; required washout = 10 days (1.5 weeks)
  • 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 while on study therapy and for 12 week following their last dose of study medication.

Exclusion Criteria:

  • Patients who cannot comply with protocol requirements including clinic visits for intravenous infusions and birth control measures may not be enrolled.
  • Female patients who are pregnant or are breast feeding.
  • Potential patients with a history of another cancer other than basal cell carcinoma or cervical intraepithelial neoplasia (cervical cancer in situ) may not be enrolled unless it is documented that their previous cancer was treated, they have been disease free for five or more years prior to starting this study and they are in their doctor's judgment at less than 30% risk of relapse of this previous malignancy.
  • Patients with a peripheral blood total lymphocyte count of higher than 25,000/mm3 may not be enrolled.
  • Patients cannot have experienced a significant (CTCAE Grade 3 or 4 with or without neutropenia) infection within 2 weeks of their first dose of MT-3724.
  • Patients are not eligible if they are using any other approved or investigational anti-neoplastic therapies or any other investigational therapies for any other reason.
  • Patients may not be receiving systemic corticosteroid therapy at a prednisone dose > 20 mg/day (or steroid equivalent) within 2 weeks of starting study.
  • 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.
  • 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.
  • Patients with known active Hepatitis C, HIV or a present history of Hepatitis B
  • Patients 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.
  • Patients with a suspected allergy or sensitivity to any component of MT-3724 drug preparation based upon known allergies to compounds of a similar class who have had an anaphylactic or other severe infusion reaction to human immunoglobulin or monoclonal antibody administration are n ot eligible.
  • Patients who have had an allogeneic hematopoietic stem cell transplantation are not eligible.
  • Patients 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 after MT-3724 has finished.
  Contacts and Locations
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


Contacts
Contact: Nenad Sarapa, MD nenad.sarapa@mtem.com
Contact: Kristina Dabovic, PharmD kristina.dabovic@mtem.com

Locations
United States, Arizona
University of Arizona Recruiting
Tucson, Arizona, United States, 85724
Contact: Daniel Persky, MD         
Contact: Diane Rensvold    520-684-9055    drensvold@uacc.arizona.edu   
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States
Contact: Paul Hamlin, MD         
New York University Langone Medical Center Suspended
New York, New York, United States
United States, North Carolina
University of North Carolina Suspended
Chapel Hill, North Carolina, United States, 27599
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States
Contact: Michelle Fanale, MD         
Sponsors and Collaborators
Molecular Templates, Inc.
Investigators
Study Director: Nenad Sarapa, MD Molecular Templates, Inc.
  More Information

Responsible Party: Molecular Templates, Inc.
ClinicalTrials.gov Identifier: NCT02361346     History of Changes
Other Study ID Numbers: MT-3724_NHL_001
First Submitted: February 3, 2015
First Posted: February 11, 2015
Last Update Posted: December 11, 2017
Last Verified: December 2017

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

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, Non-Hodgkin