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Trial record 4 of 5 for:    molecular templates | lymphoma

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

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ClinicalTrials.gov Identifier: NCT03488251
Recruitment Status : Recruiting
First Posted : April 4, 2018
Last Update Posted : November 8, 2019
Sponsor:
Information provided by (Responsible Party):
Molecular Templates, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-hodgkin Lymphoma,B Cell Refractory Diffuse Large B-Cell Lymphoma Relapsed Diffuse Large B-Cell Lymphoma Drug: MT-3724 Phase 2

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 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 B Cell Non-Hodgkin's Lymphoma
Actual Study Start Date : August 20, 2018
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : February 15, 2022


Arm Intervention/treatment
Experimental: MT-3724 10mcg/kg-GEMOX
MT-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.
Drug: MT-3724
Experimental treatment with MT-3724 in combination with GEMOX therapy.
Other Name: Gemcitabine and Qxaliplatin (GEMOX)

Experimental: MT-3724 25mcg/kg-GEMOX
MT-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.
Drug: MT-3724
Experimental treatment with MT-3724 in combination with GEMOX therapy.
Other Name: Gemcitabine and Qxaliplatin (GEMOX)

Experimental: MT-3724 50mcg/kg- GEMOX
MT-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.
Drug: MT-3724
Experimental treatment with MT-3724 in combination with GEMOX therapy.
Other Name: Gemcitabine and Qxaliplatin (GEMOX)




Primary Outcome Measures :
  1. 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)

  2. Safety measured by number of subjects with Adverse Events using CTCAE [ Time Frame: 28 days ]
    Safety measured by number of subjects with Adverse Events using CTCAE Version 5.0


Secondary Outcome Measures :
  1. PK as measured by concentrations of free MT-3724 (Maximum Plasma Concentration [Cmax]) [ Time Frame: Day 1, 5, and 12 ]
    Evaluation of the pharmacokinetic profile of MT-3724

  2. PK as measured by concentrations of free MT-3724 (Area Under the Curve [AUC]) [ Time Frame: Day 1, 5, and 12 ]
    Evaluation of the pharmacokinetic profile of MT-3724

  3. 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 ]
    Evaluation of the pharmacokinetic profile of MT-3724

  4. PD as measured by tumor response [ Time Frame: Day 28 ]
    Evaluation of the pharmacodynamic profile of MT-3724

  5. 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 ]
    Evaluation of the pharmacodynamic profile of MT-3724

  6. 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 ]
    Evaluation of the pharmacodynamic profile of MT-3724

  7. 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 ]
    Evaluation of the pharmacodynamic profile of MT-3724

  8. Tumor Response as measured by PET or CT scan [ Time Frame: Day 28 ]
    Evaluation of tumor response using International Working Group Response Criteria



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.


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

Inclusion Criteria:

  1. Be adequately informed about the study and fully consent to participation as demonstrated by signing the written informed consent form before any screening procedure.
  2. Be aged ≥18 years on the date of signing the informed consent form.
  3. Have relapsed or refractory B-cell NHL that, in the investigator's opinion, could benefit from MT-3724+GEMOX therapy. At least one histologically documented relapse of NHL, by:

    1. Bone marrow biopsy (FNA is not acceptable) or
    2. Excisional lymph node biopsy or
    3. Core biopsy of any involved organ (FNA not acceptable)
    4. CD20-positive histology must have been confirmed at any time during NHL disease course and documented in the medical history
    5. If no histology is available after any relapse the investigator can consult the medical monitor to discuss if the patient can be included
  4. All subtypes of B-cell NHL may be considered for Part 1 (MT-3724 dose escalation). Only histologically documented DLBCL (including mixed histology) may be considered for Part 2 (expansion cohort).
  5. Have received all approved therapies for NHL that are applicable for the patient in the opinion of the treating physician.

    1. Patients refractory to treatment are eligible.
    2. Patient who have progressed following CAR T-cell therapy are also eligible.
  6. Have measurable disease by Lugano Classification for NHL

    1. >1.5 cm longest diameter (LDi) for lymph nodes
    2. >1 cm LDi for extranodal disease
  7. Have ECOG performance score of ≤2.
  8. Have adequate bone marrow function, as determined by:

    1. Absolute neutrophil count (ANC) ≥1,000/mm3 and
    2. Platelet count ≥50,000 mm³
  9. Have adequate kidney function, assessed by the estimated glomerular filtration rate (eGFR) ≥60 mL/min calculated by the CPK-EPI equation .

    At the investigator's discretion, the eGFR result <60 mL/min may be verified by measurement of creatinine clearance (CLcr) based on the 24-hour urine collection. Subjects with CLcr ≥60 mL/min will be eligible irrespective of the eGFR result.

  10. Have adequate hepatic function, as determined by:

    1. Total bilirubin ≤1.5 x ULN, or ≤3 x ULN for subjects with Gilbert's Syndrome and
    2. Aspartate aminotransferase (AST) ≤3 x ULN (or ≤ 5.0 x ULN if liver involvement) and
    3. Alanine aminotransferase (ALT) ≤3 x ULN (or ≤ 5.0 x ULN if liver involvement).
  11. Have adequate coagulation, as determined by:

    1. INR or PT ≤1.5 x ULN
    2. aPTT ≤1.5 x ULN
  12. Have adequate serum albumin, as determined by:

    a. Albumin ≥ 3.0 g/dL

  13. Women of reproductive potential must have a negative pregnancy test during the screening period within 72 hours before the start of treatment. Women not of reproductive potential are female subjects who are postmenopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy,bilateral salpingectomy).
  14. Subjects of reproductive potential and their partners must agree to either to abstain continuously from heterosexual intercourse or to use a reliable birth control method between signing the informed consent until 6 months following the last dose of MT-3724 or GEMOX . The investigator or a designated associate should advise the subject how to achieve adequate contraception. The following birth control methods may be considered as adequate

    1. Condoms (male or female) with or without a spermicidal agent;
    2. Diaphragm or cervical cap with spermicide;
    3. Intrauterine device;
    4. Hormone-based contraception: Established use of oral, injected, or implanted hormonal methods of contraception;
    5. True abstinence;
    6. Vasectomy is an acceptable method for a male subject or male partner of a female subject.

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 during the study until the EoT 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. Any investigational drug treatment from 4 weeks or 5 half-lives of the agent before the start of treatment, whichever is longer, until the EoT Visit
  17. 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.

  18. Received any vaccines within 28 days of the start of treatment, or likely to require vaccines at any time from the start of treatment until 28 days after the last dose of MT-3724. Injectable flu vaccine (inactivated or recombinant) is permitted at the investigator's discretion
  19. 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.
  20. 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

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): NCT03488251


Contacts
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Contact: Tara Lehner, MS, PMP 215- 586-0118 tara.lehner@mtem.com
Contact: Kristina Dabovic, PharmD 862-204-7184 kristina.dabovic@mtem.com

Locations
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United States, California
UC Irvine Health / Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Contact: Michelle Perez    714-509-2414    michelrp@uci.edu   
Principal Investigator: Elizabeth Brem, MD         
Sarcoma Oncology Recruiting
Santa Monica, California, United States, 90403
Contact: Victoria Chua-Alala       vchua@sarcomaoncology.com   
Principal Investigator: Sant Chawla         
United States, Illinois
Rush University Recruiting
Chicago, Illinois, United States, 60612
Contact: Tami Burge       tonya_m_burge@rush.edu   
Principal Investigator: Deborah Katz         
United States, Indiana
Indiana Blood and Marrow Transplantation Terminated
Indianapolis, Indiana, United States, 46237
United States, North Carolina
Duke Cancer Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Peggy Alton    919-668-0657    peggy.alton@duke.edu   
Principal Investigator: Matthew McKinney         
United States, Ohio
Good Samaritan Hospital Terminated
Cincinnati, Ohio, United States, 45220
Sponsors and Collaborators
Molecular Templates, Inc.

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Responsible Party: Molecular Templates, Inc.
ClinicalTrials.gov Identifier: NCT03488251     History of Changes
Other Study ID Numbers: MT-3724_NHL_002
First Posted: April 4, 2018    Key Record Dates
Last Update Posted: November 8, 2019
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Molecular Mechanisms of Pharmacological Action
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs