Clinical Trials /

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

NCT03488251

Description:

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.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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 (MT-3724_NHL_002)
  • Official Title: 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 CD20-positive B Cell Non-Hodgkin's Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: MT-3724_NHL_002
  • NCT ID: NCT03488251

Conditions

  • Non-hodgkin Lymphoma,B Cell
  • Refractory Diffuse Large B-Cell Lymphoma
  • Relapsed Diffuse Large B-Cell Lymphoma

Interventions

DrugSynonymsArms
MT-3724MT-3724 10mcg/kg-GEMOX

Purpose

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 CD20-positive B-Cell NHL.

Detailed Description

      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 CD20 positive 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 day cycles (approximately 4 months).
    

Trial Arms

NameTypeDescriptionInterventions
MT-3724 10mcg/kg-GEMOXExperimentalMT-3724 10 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks) of each 28 day cycle in combination with GEMOX. If the treatment with MT-3724 is continued to Cycle 3 and Cycle 4, then MT-3724 will be administered weekly (Day 1, 8, 15 and 22) of each 28-day cycle.
  • MT-3724
MT-3724 25mcg/kg-GEMOXExperimentalMT-3724 25 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks) of each 28 day cycle in combination with GEMOX. If the treatment with MT-3724 is continued to Cycle 3 and Cycle 4, then MT-3724 will be administered weekly (Day 1, 8, 15 and 22) of each 28-day cycle.
  • MT-3724
MT-3724 50mcg/kg- GEMOXExperimentalMT-3724 50 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks) of each 28 day cycle in combination with GEMOX. If the treatment with MT-3724 is continued to Cycle 3 and Cycle 4, then MT-3724 will be administered weekly (Day 1, 8, 15 and 22) of each 28-day cycle.
  • MT-3724

Eligibility Criteria

        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 CD20-positive B-cell NHL may be
             considered for Part 1 (MT-3724 dose escalation). Only CD20-positive DLBCL may be
             considered for Part 2 (expansion cohort)

          3. Intermediate or high risk by Ann Arbor Staging with Cotswold Modifications that meets
             criteria for active disease requiring therapy.

          4. 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.

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

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

          7. 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.

        Exclusion criteria:

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

          -  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.

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

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

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

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

          -  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.

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

          -  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

          -  Women who are pregnant or breastfeeding.

          -  History or current evidence of hypersensitivity to components of the investigational
             product or significant (CTCAE Grade ≥2) allergy to any other allergen.

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

               1. Rituximab (Rituxan®): 110 days; if a subject had received rituximab within
                  111-365 days before the start of treatment, then a serum rituximab level must be
                  documented to be <500 ng/mL during the screening period

               2. Obinutuzumab (Gazyva®): 184 days

               3. Ofatumumab (Arzerra®): 88 days

          -  Received therapy for NHL (except anti-CD20 Mab listed above) within 3 weeks or 5
             half-lives of the agent before the start of treatment, whichever is longer.

          -  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.

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

          -  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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tolerability as measured by number of subjects with dose limiting toxicities
Time Frame:28 days
Safety Issue:
Description:Evaluation of tolerability of MT-3724 measured by number of subjects with dose limiting toxicities (DLTs)

Secondary Outcome Measures

Measure:PK as measured by concentrations of free MT-3724 (Maximum Plasma Concentration [Cmax])
Time Frame:Day 1, 5, and 12
Safety Issue:
Description:Evaluation of the pharmacokinetic profile of MT-3724
Measure:PK as measured by concentrations of free MT-3724 (Area Under the Curve [AUC])
Time Frame:Day 1, 5, and 12
Safety Issue:
Description:Evaluation of the pharmacokinetic profile of MT-3724
Measure:PK as measured by concentrations of free MT-3724 (Time to reach maximum concentration after drug administration [Tmax])
Time Frame:Day 1, 5, and 12
Safety Issue:
Description:Evaluation of the pharmacokinetic profile of MT-3724
Measure:PD as measured by tumor response
Time Frame:Day 28
Safety Issue:
Description:Evaluation of the pharmacodynamic profile of MT-3724
Measure:PD as measured by MT-3724 [anti-drug antibody (ADA) titer and neutralizing antibody (NA)]
Time Frame:Screening, Day 1 of each cycle and 2-3 weeks after last dose
Safety Issue:
Description:Evaluation of the pharmacodynamic profile of MT-3724
Measure:PD as measured by B-cell count in peripheral blood as determined by flow cytometry measured against MT-3724 serum concentrations at pre-specified time points
Time Frame:Screening, Day 1 of each cycle, Day 12 of Cycles 1-2, Day 15 of Cycles 3-4 and 2-3 weeks after last dose
Safety Issue:
Description:Evaluation of the pharmacodynamic profile of MT-3724
Measure:PD as measured by by immunophenotype in peripheral blood, as determined by flow cytometry measured against MT-3724 serum concentrations at pre-specified time points
Time Frame:Screening, Day 1 of each cycle, Day 12 of Cycles 1-2, Day 15 of Cycles 3-4 and 2-3 weeks after last dose
Safety Issue:
Description:Evaluation of the pharmacodynamic profile of MT-3724
Measure:Tumor Response as measured by PET or CT scan
Time Frame:Day 28
Safety Issue:
Description:Evaluation of tumor response using International Working Group Response Criteria

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Molecular Templates, Inc.

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