Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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.

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.

Part 3

Inclusion Criteria:

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. 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 screening

a. 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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
MT-3724 Phase 1 5 mcg/kg/dose
Phase 1: MT-3724 5 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 M-W-F X 2 weeks; 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
MT-3724 Phase 1 10 mcg/kg/dose
Phase 1: MT-3724 10 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 M-W-F X 2 weeks; 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
MT-3724 Phase 1 20 mcg/kg/dose
Phase 1: MT-3724 20 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 M-W-F X 2 weeks; 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
MT-3724 Phase 1 50 mcg/kg/dose
Phase 1: MT-3724 50 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 M-W-F X 2 weeks; 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
MT-3724 Phase 1 100 mcg/kg/dose
Phase 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 M-W-F X 2 weeks; 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
MT-3724 Phase 1 75 mcg/kg/dose
Phase 1b: MT-3724 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 Phase 1 portion of the study)
  • Drug: MT-3724 Phase 1
    Intravenous dosing M-W-F X 2 weeks; 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
MT-3724 Phase 1b 50 mcg/kg/dose
Phase 1b: MT-3724 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
  • Drug: MT-3724 Phase 1
    Intravenous dosing M-W-F X 2 weeks; 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
MT-3724 Phase 2 50 mcg/kg/dose
Phase 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 2
    Intravenous dosing on M-W-F x 2 weeks; 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.

Recruiting Locations

UT Health San Antonio Cancer
San Antonio, Texas 78229
Contact:
Patricia Manea
210-450-1000
maneap@uthscsa.edu

More Details

Status
Recruiting
Sponsor
Molecular Templates, Inc.

Study Contact

Kristina Dabovic, PharmD
kristina.dabovic@mtem.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.