PK,PD, Safety and Tolerability of Multiple Dose Regimens of MT-3724 With Gemcitabine and Oxaliplatin for the Treatment of Patients With Relapsed/Refractory Diffuse Large B Cell Non-Hodgkin's Lymphoma



Status:Recruiting
Conditions:Lymphoma, Lymphoma
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:2/27/2019
Start Date:August 20, 2018
End Date:February 15, 2022
Contact:Tara Lehner, MS, PMP
Email:tara.lehner@mtem.com
Phone:215- 586-0118

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Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Multiple Dose Regimens of MT-3724 With Gemcitabine and Oxaliplatin for the Treatment of Subjects With Relapsed or Refractory B Cell Non-Hodgkin's Lymphoma

The purpose of this study is to evaluate the safety and tolerability of MT-3724 in
combination with gemcitabine and oxaliplatin (GEMOX) in subjects with relapsed or refractory
B-Cell NHL.

This is a multi-center, open-label two-part study evaluating the safety and tolerability of
MT-3724 in combination with GEMOX in relapsed or refractory B-cell Lymphoma patients.

Part 1: (MT-3724 Dose Escalation) Define the maximum tolerated dose (MTD) of MT-3724 in
combination with standard treatment of GEMOX

Part 2: (MTD Expansion Cohort) Confirm the safety and tolerability of the MTD of MT-3724 from
Part 1 in the MTD Expansion Cohort, where MT-3724 will be given at the MTD in combination
with GEMOX. In addition, the PK, PD, immunogenicity and tumor response at the MTD of MT-3724
in combination with GEMOX will be more thoroughly evaluated in Part 2.

It is anticipated that up to 64 patients will be enrolled. Treatment will continue for up to
four 28 days cycles. If the subject exhibits SD, CR or PR after the end of Cycle 4 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. Continuation of GEMOX is at
investigators discretion.

Inclusion Criteria:

1. Men or Women, age 18 years or older

2. 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 Part 1 (MT-3724 dose escalation). Only DLBCL may be considered for Part 2
(expansion cohort)

3. Subjects must have received all available approved therapies for NHL. Those subjects
who are ineligible for approved therapies in the opinion of the investigator, or have
refused such therapies, will be eligible.

4. Measurable disease (≥1 cm) by Lugano Classification for NHL.

5. Eastern Cooperative Oncology Group (ECOG) performance score of ≤2.

6. Female patients of childbearing potential must have a negative serum or urine
pregnancy test within 7 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.

7. Adequate kidney function, assessed by the estimated glomerular filtration rate (eGFR)
≥60 mL/minmCPK-EPI equation.

Exclusion criteria:

1. Patients who cannot comply with protocol requirements including clinic visits for
intravenous infusions and birth control measures may not be enrolled.

2. 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, or any other previous cancer
curatively treated >2 years before the start of treatment.

3. Current evidence of new or growing brain or spinal metastases during screening.

4. History of allogeneic hematopoietic stem cell transplant within 180 days before the
start of treatment.

5. Current evidence of acute or chronic Graft versus Host Disease.

6. Current evidence of CTCAE Grade >1 toxicity (except for hair loss, and those
toxicities listed in other eligibility criteria) before the start of treatment.

7. Current evidence of incomplete recovery from surgery before the start of treatment, or
planned surgery at any time until the Last Study Assessment Visit, except minor
elective interventions deemed acceptable by the investigator.

8. History or current evidence of significant (CTCAE Grade ≥2) infection or wound within
4 weeks before the start of treatment.

9. 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.

10. 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.

11. Patients with known active Hepatitis C, HIV or a present history of Hepatitis B

12. Women who are pregnant or breastfeeding.

13. History or current evidence of hypersensitivity to any study drugs, or current
evidence of hypersentivity requiring systemic steroid doses ≥20 mg/day Prednisone
equivalent

14. Received any amount of anti-CD20 MAb therapy within the following periods before the
start of treatment

1. Rituximab (Rituxan®): 84 days; if a subject had received rituximab within 37
Weeks before the start of treatment, 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

15. Received therapy for NHL (except anti-CD20 Mab listed above) within 4 weeks before the
start of treatment

16. Received radiotherapy to tumor lesions that would be chosen as target lesions
(measurable disease) within 4 weeks before the start of treatment, unless the lesion
exhibited objective progression between the radiotherapy and the screening according
to the Lugano Classification for NHL.

a. Palliative radiotherapy to non-target lesions is allowed at the investigator's
discretion after consultation with the Medical Monitor and sponsor.

17. Received systemic immune modulators within 2 weeks before the start of treatment
including but not limited to systemic corticosteroids >20 mg/day of prednisone
equivalent, cyclosporine and tacrolimus. Corticosteroids for pre-medication and NSAIDs
are permitted.

18. Received any investigational drug treatment within 4 weeks or within 5 half-lives of
the therapeutic agent before the start of treatment, whichever is longer, until EoT
Visit
We found this trial at
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Cincinnati, Ohio 45220
Principal Investigator: Saulius Girnius
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Durham, North Carolina 27710
Principal Investigator: Matthew McKinney
Phone: 919-668-0657
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Indianapolis, Indiana 46237
Principal Investigator: Anand Tandra
Phone: 317-528-7298
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Orange, California 92868
Principal Investigator: Elizabeth Brem, MD
Phone: 714-509-2414
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Orange, CA
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