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 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: MT-3724_NHL_002
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 9

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 participants with relapsed or refractory B-Cell NHL.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Part 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs)

  A DLT is any treatment-emergent adverse event (TEAE) that occurred after the start of infusion in cycle 1 of Part 1 and the TEAE is at least possibly related to the study drug, as determined by the sponsor after consultation with the investigator(s).

  Up to 168 Days

• Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  An AE is as any untoward medical occurrence in a participant or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental intervention(s). A SAE is any AE that is fatal or life-threatening, permanently disabling (incapacitating or interfering with the ability to resume usual life patterns), results in unplanned in-subject hospitalization or prolongation of an existing hospitalization, results in a congenital abnormality or birth defect, or any other situation that require medical or scientific judgement. Number of participants with common \>=0 percent (%) TEAEs and SAEs are presented.

  Up to 168 Days

Secondary Outcomes (10)

• Part 1 and 2: Maximum Concentration (Cmax) Following Administration of MT-3724

  Cycle(C)1:Day1:Predose,10 minutes(min) before end of treatment(EOT),5,30 min,1,2,3,4 hours after EOT,Days5,12:Predose,10 min before EOT,5min,2hours after EOT;C2,C3,C4:Day1:Predose,10min before EOT,5 min after EOT(C1 is 42-days;C2,C3,C4 are 28-days cycles)

• Part 1 and 2: Area Under the Plasma Concentration Time Curve (AUC) Following Administration of MT-3724

  Cycle(C)1:Day1:Predose,10 minutes(min) before end of treatment(EOT),5,30 min,1,2,3,4 hours after EOT,Days5,12:Predose,10 min before EOT,5min,2hours after EOT;C2,C3,C4:Day1:Predose,10min before EOT,5 min after EOT(C1 is 42-days;C2,C3,C4 are 28-days cycles)

• Part 1 and 2: Time to Maximum Plasma Concentration (Tmax) Following Administration of MT-3724

  Cycle(C)1:Day1:Predose,10 minutes(min) before end of treatment(EOT),5,30 min,1,2,3,4 hours after EOT,Days5,12:Predose,10 min before EOT,5min,2hours after EOT;C2,C3,C4:Day1:Predose,10min before EOT,5 min after EOT(C1 is 42-days;C2,C3,C4 are 28-days cycles)

• Part 1 and 2: Number of Participants With Immunophenotyping Data Outside the Reference Range

  Up to 168 Days

• Part 1 and 2: Number of Participants With Anti-drug Antibody Titer

  Up to 168 Days

Study Arms (4)

Part 1: Cohort 1: MT-3724 10 mcg/kg/ GEM/ OX

EXPERIMENTAL

In original protocol and amendment 2, participants will be administered intravenous (IV) MT-3724 10 micrograms per kilograms (mcg/kg) over 1 hour on Days 1, 3, 5, 8, 10 and 12 in Cycles 1 and 2 (each 28-day cycle) and on Days 1, 8, 15, and 22 in Cycles 3 and 4 (each 28-day cycle). Participants will also be administered Gemcitabine 1000 milligrams per meter square (mg/m\^2) as 30-minute IV infusion and Oxaliplatin 100 mg/m\^2 as 2-hour IV infusion on Days 2 and 16 in Cycles 1, 2, 3 and 4 (each 28-day cycle). Per amendment 2, participants will be administered MT-3724 10 mcg/kg on Days 1, 3, 5, 8, 10, 12, 15, 22, 29, and 36 in Cycle 1 (42-day cycle). In Cycles 2, 3 and 4, MT-3724 10 mcg/kg will be administered weekly on Days 1, 8, 15, and 22 of each 28-day cycle. Gemcitabine and oxaliplatin will be administered on Days 16 and 30 of Cycle 1 and on Days 2 and 16 in Cycles 2, 3 and 4 (42-day cycle for Cycle 1 and 28-day cycle for Cycle 2, Cycle 3 and Cycle 4).

Drug: MT-3724; Drug: Gemcitabine; Drug: Oxaliplatin

Part 1: Cohort 2: MT-3724 25 mcg/kg/ GEM/ OX

EXPERIMENTAL

In original protocol and amendment 2, participants will be planned to administer IV MT-3724 25 mcg/kg over 1 hour on Days 1, 3, 5, 8, 10 and 12 in Cycles 1 and 2 (each 28-day cycle) and on Days 1, 8, 15, and 22 in Cycles 3 and 4 (each 28-day cycle). Participants will also be planned to administer Gemcitabine 1000 mg/m\^2 as 30-minute IV infusion and Oxaliplatin 100 mg/m\^2 as 2-hour IV infusion on Days 2 and 16 in Cycles 1, 2, 3 and 4 (each 28-day cycle). Per amendment 2, participants will be planned to administer MT-3724 25 mcg/kg on Days 1, 3, 5, 8, 10, 12, 15, 22, 29, and 36 in Cycle 1 (42-day cycle). In Cycles 2, 3 and 4, MT-3724 25 mcg/kg will be planned to administer weekly on Days 1, 8, 15, and 22 of each 28-day cycle. Gemcitabine and oxaliplatin will be planned to administer on Days 16 and 30 of Cycle 1 and on Days 2 and 16 in Cycles 2, 3 and 4 (42-day cycle for Cycle 1 and 28-day cycle for Cycle 2, Cycle 3 and Cycle 4).

Drug: MT-3724; Drug: Gemcitabine; Drug: Oxaliplatin

Part 1: Cohort 3: MT-3724 50 mcg/kg/ GEM/ OX

EXPERIMENTAL

In original protocol and amendment 2, participants will be planned to administer IV MT-3724 50 mcg/kg over 1 hour on Days 1, 3, 5, 8, 10 and 12 in Cycles 1 and 2 (each 28-day cycle) and on Days 1, 8, 15, and 22 in Cycles 3 and 4 (each 28-day cycle). Participants will also be planned to administer Gemcitabine 1000 mg/m\^2 as 30-minute IV infusion and Oxaliplatin 100 mg/m\^2 as 2-hour IV infusion on Days 2 and 16 in Cycles 1, 2, 3 and 4 (each 28-day cycle). Per amendment 2, participants will be planned to administer MT-3724 50 mcg/kg on Days 1, 3, 5, 8, 10, 12, 15, 22, 29, and 36 in Cycle 1 (42-day cycle). In Cycles 2, 3 and 4, MT-3724 50 mcg/kg will be planned to administer weekly on Days 1, 8, 15, and 22 of each 28-day cycle. Gemcitabine and oxaliplatin will be planned to administer on Days 16 and 30 of Cycle 1 and on Days 2 and 16 in Cycles 2, 3 and 4 (42-day cycle for Cycle 1 and 28-day cycle for Cycle 2, Cycle 3 and Cycle 4).

Drug: MT-3724; Drug: Gemcitabine; Drug: Oxaliplatin

Part 2: MT-3724/ GEM/ OX

EXPERIMENTAL

Participants will be planned to administer Maximum tolerated dose (MTD) of MT-3724 in combination with Gemcitabine and Oxaliplatin (GEMOX).

Drug: MT-3724; Drug: Gemcitabine; Drug: Oxaliplatin

Interventions

MT-3724 DRUG

MT-3724 will be administered.

Part 1: Cohort 1: MT-3724 10 mcg/kg/ GEM/ OX; Part 1: Cohort 2: MT-3724 25 mcg/kg/ GEM/ OX; Part 1: Cohort 3: MT-3724 50 mcg/kg/ GEM/ OX; Part 2: MT-3724/ GEM/ OX

Gemcitabine DRUG

Gemcitabine will be administered.

Part 1: Cohort 1: MT-3724 10 mcg/kg/ GEM/ OX; Part 1: Cohort 2: MT-3724 25 mcg/kg/ GEM/ OX; Part 1: Cohort 3: MT-3724 50 mcg/kg/ GEM/ OX; Part 2: MT-3724/ GEM/ OX

Oxaliplatin DRUG

Oxaliplatin will be administered.

Part 1: Cohort 1: MT-3724 10 mcg/kg/ GEM/ OX; Part 1: Cohort 2: MT-3724 25 mcg/kg/ GEM/ OX; Part 1: Cohort 3: MT-3724 50 mcg/kg/ GEM/ OX; Part 2: MT-3724/ GEM/ OX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be adequately informed about the study and fully consent to participation as demonstrated by signing the written informed consent form before any screening procedure.
• Be aged ≥18 years on the date of signing the informed consent form.
• 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:
• Bone marrow biopsy (FNA is not acceptable) or
• Excisional lymph node biopsy or
• Core biopsy of any involved organ (FNA not acceptable)
• CD20-positive histology must have been confirmed at any time during NHL disease course and documented in the medical history
• If no histology is available after any relapse the investigator can consult the medical monitor to discuss if the patient can be included
• 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).
• Have received all approved therapies for NHL that are applicable for the patient in the opinion of the treating physician.
• Patients refractory to treatment are eligible.
• Patient who have progressed following CAR T-cell therapy are also eligible.
• Have measurable disease by Lugano Classification for NHL
• \>1.5 cm longest diameter (LDi) for lymph nodes
• \>1 cm LDi for extranodal disease

You may not qualify if:

• 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
• 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.
• 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 any study drugs, or current evidence of hypersensitivity requiring systemic steroid doses ≥20 mg/day Prednisone equivalent
• Received any amount of anti-CD20 MAb therapy within the following periods before the start of treatment
• 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
• Obinutuzumab (Gazyva®): 184 days

Sponsors & Collaborators

• Molecular Templates, Inc.: lead

Study Sites (9)

UC Irvine Health / Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Sarcoma Oncology

Santa Monica, California, 90403, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, 46237, United States

Location

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Good Samaritan Hospital

Cincinnati, Ohio, 45220, United States

Location

UT Southwestern Medical Center Clinical Research

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Gemcitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Molecular Templates, Inc.

trials@mtem.com

512 930-0304

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: April 4, 2018
• Study Start: August 20, 2018
• Primary Completion: March 12, 2021
• Study Completion: March 12, 2021
• Last Updated: August 16, 2022
• Results First Posted: August 16, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)