Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Multiple Dose Regimens of MT-3724 With Lenalidomide for the Treatment of Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (MT-3724_NHL_003)

NCT03645395 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: MT-3724_NHL_003
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of MT-3724 in combination with Lenalidomide in participants with relapsed or refractory B-Cell NHL.

Conditions

Non-hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• Part 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) and Dose-limiting Toxicity

  An adverse event is any untoward medical occurrence 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 treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention. A DLT is any 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 1 year

• Part 1 and 2: Number of Participants With Abnormal Laboratory Parameters

  Laboratory parameters included hematology, blood chemistry, and urinalysis. Any abnormal laboratory test results which were considered clinically significant by the investigator were recorded on the case report form. Number of participants with any clinically significant abnormalities in laboratory parameters have been presented.

  Up to 1 year

• Part 1 and 2: Number of Participants With Clinically Significant Physical Findings

  This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.

  Up to 1 year

Secondary Outcomes (8)

• Part 1 and 2: Plasma Concentrations of MT-3724

  Days 1,3 and 12 of treatment cycle (Each cycle is of 28 days); Up to 1 year

• Part 1 and 2: Change From Baseline in B-cell Count

  Up to 1 year

• Part 1 and 2: Number of Participants With Anti-drug Antibody Titer When Treated With MT-3724

  Up to 1 year

• Part 1 and 2: Number of Participants With Neutralizing Antibody (NAb) Titers When Treated With MT-3724

  Up to 1 year

• Part 1 and 2: Number of Participants With Objective Response Rate (ORR)

  Up to 1 year

Study Arms (5)

MT-3724 10 mcg/kg-LEN

EXPERIMENTAL

MT-3724 10 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks on Days 1, 3, 5, 8, 10, and 12) of each 28 day cycle in combination with LEN. If the treatment with MT-3724 is continued beyond Cycle 2, then MT-3724 will be administered weekly (Days 1, 3, 5, 8, 10, and 12) of each 28-day cycle

Drug: MT-3724

MT-3724 25 mcg/kg-LEN 3x a week

EXPERIMENTAL

MT-3724 25 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks on Days 1, 3, 5, 8, 10, and 12) of each 28 day cycle in combination with LEN. If the treatment with MT-3724 is continued beyond Cycle 2, then MT-3724 will be administered weekly Days 1, 3, 5, 8, 10, and 12) of each 28-day cycle

Drug: MT-3724

MT-3724 20 mcg/kg-LEN 3x a week

EXPERIMENTAL

MT-3724 20 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks on Days 1, 3, 5, 8, 10, and 12) of each 28 day cycle in combination with LEN. If the treatment with MT-3724 is continued beyond Cycle 2 , then MT-3724 will be administered weekly (Days 1, 3, 5, 8, 10, and 12) of each 28-day cycle

Drug: MT-3724

MT-3724 25 mcg/kg-LEN 2x a week

EXPERIMENTAL

MT-3724 25 mcg/kg dose IV for 4 doses (days 1, 5, 8 and 12 during cycles 1 and 2) of each 28 day cycle in combination with LEN and weekly during cycles 3 and beyond (days 1, 8, 15 and 22).

Drug: MT-3724

MT-3724 50 mcg/kg-LEN

EXPERIMENTAL

MT-3724 50 mcg/kg dose IV for 4 doses (days 1, 5, 8 and 12 during cycles 1 and 2) of each 28 day cycle in combination with LEN and weekly during cycles 3 and beyond (days 1, 8, 15 and 22).

Drug: MT-3724

Interventions

MT-3724 DRUG

Experimental treatment with MT-3724 in combination with LEN therapy.

MT-3724 10 mcg/kg-LEN; MT-3724 20 mcg/kg-LEN 3x a week; MT-3724 25 mcg/kg-LEN 2x a week; MT-3724 25 mcg/kg-LEN 3x a week; MT-3724 50 mcg/kg-LEN

Eligibility Criteria

• Age: 18 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Participants must meet ALL the following criteria to be eligible for the study.
• Be adequately informed about the study and fully consent to participation as demonstrated by signing the written ICF before any screening procedure.
• Be aged ≥18 years years on the date of signing the informed consent form.
• Have relapsed or refractory CD20 positive B-cell NHL that, in the investigator's opinion, could benefit from MT-3724+LEN therapy. Participants must have proof of CD20 positive NHL either by:
• Historical biopsies (obtained with diagnosis of relapsed or refractory disease), or
• Fresh biopsies.
• Bone marrow biopsy
• Excisional lymph node biopsy
• Core biopsy of any involved organ; all are acceptable methods; FNA not acceptable
• 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 (MTD expansion cohort).
• Have received all available approved therapies for NHL, one of which should be anti-CD20 based therapy.
• Participants whose prior therapy includes chimeric antigen receptor t-cell (CAR-T) cell therapy are eligible.
• Have bi-dimensionally measurable disease by Lugano Classification for NHL:
• \>1.5 cm LDi for lymph nodes
• \>1.0 cm LDi for extra nodal disease.

You may not qualify if:

• Participants who meet any of the following criteria must be excluded from the study.
• Medical and surgical history
• 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. Participants with prior, curatively treated cancer \>2 years ago before the start of treatment can be enrolled.
• Current evidence of new or growing brain or spinal metastases during screening. Participants with known brain or spinal metastases may be eligible if they:
• Had radiotherapy or another appropriate therapy for the brain or spinal metastases; concurrent prophylactic treatment is allowed.
• Neurological symptoms must be stable and no worse than grade 2
• Have evidence of stable brain or spinal disease on computer topography (CT) or magnetic resonance imaging (MRI) scan obtained within 4 weeks of signing the ICF and compared with prior imaging results.
• Do not require chronic steroid therapy, or if applicable, have been stable on steroid dose of no more than prednisone 20mg/day or equivalent by C1D1.
• Current evidence of Graft versus Host Disease.
• Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) Grade \>1 toxicity (before the start of treatment, except for hair loss, and those Grade 2 toxicities listed as permitted in other eligibility criteria).
• Current evidence of incomplete recovery from surgery or radiotherapy before the start of treatment, or planned surgery or radiotherapy at any time during the study until the EoT Visit, except minor elective interventions deemed acceptable by the investigator.
• Current evidence of significant (CTCAE Grade ≥2) infection or wound within 4 weeks before the start of treatment.
• a. Participants with Grade 2 infection that has stabilized or improved with oral anti-infectives before the start of treatment may be eligible at the sponsor's discretion
• Current evidence of significant cardiovascular disease including, but not limited to the following conditions:
• Unstable angina (symptoms of angina at rest) or new-onset angina within ≤3 months before the start of treatment.

Sponsors & Collaborators

• Molecular Templates, Inc.: lead

Study Sites (5)

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Boca Raton Clinical Research

Plantation, Florida, 33322, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

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

trials@mtem.com

862-204-7184

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: July 19, 2018
• First Posted: August 24, 2018
• Study Start: April 8, 2019
• Primary Completion: March 10, 2021
• Study Completion: March 10, 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 (5)