Safety, PD & Efficacy of MT-3724 for the Treatment of Patients With Relapsed or Refractory DLBCL

Stopped early · Phase 1/Phase 2

Conditions studied: Non-Hodgkin's B-cell Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Small Lymphocytic Leukemia, Diffuse Large B Cell Lymphoma, Blood Cancer, Hematological Malignancy

In brief

The purpose of this study is to evaluate the safety and tolerability of MT-3724 in subjects with relapsed or refractory B-Cell NHL or relapsed and refractory CLL (Part 1 only) and relapsed and refractory DLBCL (Part 2 and Part 3). Part 3 evaluates the efficacy of MT-3724.

Key facts

Study ID

NCT02361346

Run by

Molecular Templates, Inc.

People needed

38

Starts

2015-02-01

Expected to finish

2021-03-22

Last updated by the study team

2022-08-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must be informed about the study and fully consent to participation as demonstrated by signing the written ICF before any screening procedure.
• Male and female participants >= 18 years of age at the time of informed consent.
• Participants must have relapsed or refractory Diffuse large B cell lymphoma (DLBCL) according to the Revised European American Lymphoma/World Health Organization classification. Participants must have proof of cluster of differentiation 20 plus (CD20+) DLBCL, based on either:
• a. historical biopsies (obtained with diagnosis of relapsed or refractory disease), or
• b. fresh biopsies
• c. bone marrow biopsy, excisional lymph node biopsy, and core biopsy of any involved organ are all acceptable methods; Fine Needle Aspirate is not acceptable.
• Participants must have received at least 2 standard of care (SoC) regimens (including anti-CD20 antibody therapy) appropriate for DLBCL treatment.
• a. Participants whose prior therapy includes chimeric antigen receptor T-cell (CAR-T-cell) therapy are eligible.
• b. Participants who underwent stem cell transplant (SCT) > 100 days for autologous SCT or > 180 days for allogeneic SCT before study drug administration.
• c. Participants who have been ineligible for SoC DLBCL treatments may be eligible at the investigator's discretion, upon sponsor approval.
• Participants must have at least 1 bi-dimensional tumor lesion at screening that is measurable by computerized tomography (CT) and/or magnetic resonance imaging (MRI) according to the Lugano criteria. Bi-dimensionally measurable tumor lesion by CT and/or MRI is defined as longest diameter of > 1.5 centimeters (cm) for lymph nodes and > 1.0 cm for extranodal disease.
• Participants must have life expectancy of > 3 months from the start of treatment.
• Participants must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Participants must have met ALL the following laboratory criteria:
• a. absolute neutrophil count (ANC) >= 1.0 × 10\^9 cells per liter with no myeloid growth factors (granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor preparations) administered within 2 weeks of Cycle 1 Day 1.
• b. platelet count >= 50 × 10\^9 cells per liter with no Thrombopoietin-receptor agonists agents or platelet transfusions given within 2 weeks of Cycle 1 Day 1.
• c. hemoglobin >= 8.0 grams per deciliter (g/dL) with no erythropoietin stimulating agents or peripheral red blood cell (PRBC) transfusions within 2 weeks of Cycle 1 Day 1
• d. creatinine clearance (CLcr) to be >= 50 milliliter per minute (ml/min) either measured or estimated using the Cockcroft-Gault formula.
• e. total bilirubin (or direct bilirubin for patients with Gilbert's disease < 1.5 × upper limit of normal (ULN)
• f. alanine transaminase (ALT) ≤ 3.0 × ULN (or <= 5.0 x ULN if liver involvement).
• g. aspartate aminotransferase (AST) <= 3.0 × ULN (or <= 5.0 x ULN if liver involvement).
• h. international normalized ratio (INR) or prothrombin time (PT) <= 1.5 x ULN (unless on therapeutic anticoagulants).
• i. Activated partial thromboplastin time <= 1.5 x ULN (unless on therapeutic anticoagulants).
• Have adequate serum albumin, as determined by: a. albumin >= 3.0 g/dL.
• QT interval correction for heart rate using Fridericia's formula (QTcF) <= 480 milliseconds determined as the average of 3 QTcF values from the triplicate electrocardiogram (ECG) obtained at screening.

You may not qualify if…

• Prior or Current Therapies
• Received any amount of anti-CD20 monoclonal antibodies (mAbs) within the following periods before the start of treatment:
• a. Rituximab (Rituxan®/MabThera® or rituximab biosimilar): within 84 days (12 weeks); if a participant has received rituximab within 37 weeks before the start of treatment, then serum rituximab level must be negative (< 500 nanograms per milliliter [ng/mL]) at screening.
• b. Obinutuzumab (Gazyva®/Gazyvaro®): 184 days c. Ofatumumab (Arzerra®): 88 days d. Any other anti-CD20 agents (eg, investigational agents), the washout period is 5 half-lives. The investigator must contact the medical monitor to discuss the most Compound: MT-3724 appropriate washout for non-approved CD20-targeting agents, where the half-life (t1/2) is not known.
• Received approved or investigational treatment for DLBCL within 4 weeks before the start of treatment. For small molecules (MW < 0.9 kilodaltons [kDa]), the washout is 5 half-lives or at least 2 weeks. Radioimmunoconjugates are excluded within 12 weeks before the start of treatment.
• Received radiation therapy to tumor lesions that would serve as target lesions (measurable disease) within 4 weeks before the start of treatment, unless the lesion exhibited objective progression between radiation therapy and screening according to the Lugano Classification
• o a. Palliative radiation therapy to non-target lesions may be permitted at the investigator's discretion after consultation with the medical monitor and sponsor.
• Require the use of systemic immune modulators during study treatment:
• a. Systemic immune modulators include, but are not limited to, systemic corticosteroids at doses > 20 milligrams per day (mg/day) of prednisone equivalent, cyclosporine and tacrolimus.
• b. The use of non-steroidal anti-inflammatory drugs (NSAIDS) is permitted.
• Received any live vaccines within 4 weeks before the start of treatment.
• Prior treatment with MT-3724.
• Medical History
• Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1 toxicity (due to prior anticancer therapy) before the start of treatment, except for hair loss and those Grade 2 toxicities listed as permitted in other eligibility criteria.
• 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.
• Known or suspected hypersensitivity to the study drug or excipients contained in the study drug formulation.
• Current evidence of hypersensitivity or other underlying illness requiring systemic corticosteroids at doses > 20 mg/day prednisone equivalent.
• Current evidence of uncontrolled human immunodeficiency syndrome (HIV), hepatitis B virus (HBV) or /hepatitis C virus (HCV) at screening. Serology testing is not required if seronegativity is documented in the medical history, and if there are no clinical signs suggestive of HIV or hepatitis infections, or suspected exposure. The following exceptions apply for participants with positive viral serology:
• a. Participants with HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts >= 350 cells per milliliter may be enrolled, but must be taking appropriate opportunistic infection prophylaxis, if clinically relevant.
• b. Participants with positive HBV serology are eligible if they have an undetectable viral load and the participant will receive antiviral prophylaxis for potential HBV reactivation per institutional guidelines.
• c. Participants with positive HCV serology are eligible if quantitative polymerase chain reaction (PCR) for plasma HCV ribonucleic acid (RNA) is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.
• Current evidence of incomplete recovery from surgery or radiotherapy before start of treatment, or planned surgery or radiotherapy from the start of treatment until the end of treatment (EoT) visit, except minor elective surgery deemed acceptable by the investigator or palliative radiation therapy to non-target lesions.
• History of cardiovascular, renal, hepatic or any other disease within 3 months before the start of treatment that in the investigator's opinion, may increase the risks associated with study participation or require treatments that may interfere with the conduct of the study or the interpretation of study results.
• 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:

Where it is running

• University Hospital Vall d'Hebron (HUVH), Department of Hematology — Barcelona, Spain
• Hospital Universitario QuironSalud Madrid — Madrid, Spain
• University Hospital Virgen del Rocio (HUVR), Department of Hematology — Seville, Spain
• University of Arizona — Tucson, Arizona, United States
• Innovative Clinical Research Institute, LLC — Whittier, California, United States
• 21st Century Oncology - Jacksonville — Jacksonville, Florida, United States
• Orlando Health, Inc. — Orlando, Florida, United States
• Orlando Health, Inc. — Orlando, Florida, United States
• BRCR Medical Center — Plantation, Florida, United States
• ASCLEPES Research Centers — Weeki Wachee, Florida, United States
• Columbus Regional Research Institute — Columbus, Georgia, United States
• University of Illinois, Cancer Center — Chicago, Illinois, United States
• Healthcare Research Network III, LLC — Tinley Park, Illinois, United States
• Carle Foundation Hospital — Urbana, Illinois, United States
• Norton Healthcare, Inc — Louisville, Kentucky, United States
• New York University Langone Medical Center — New York, New York, United States
• Memorial Sloan-Kettering Cancer Center — New York, New York, United States
• University of North Carolina — Chapel Hill, North Carolina, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• UT Health San Antonio Cancer — San Antonio, Texas, United States
• Grodno University Hospital — Grodno, Belarus
• Minsk City Clinical Oncology Center — Minsk, Belarus
• Cross Cancer Institute — Edmonton, Alberta, Canada
• Cancer Centre of Southeastern Ontario at Kingston General Hospital — Kingston, Ontario, Canada
• Princess Margaret Cancer Centre — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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