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)

Stopped early · Phase 2

Conditions studied: Non-hodgkin Lymphoma

In brief

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.

Key facts

Study ID

NCT03645395

Run by

Molecular Templates, Inc.

People needed

9

Starts

2019-04-08

Expected to finish

2021-03-10

Last updated by the study team

2022-08-16

Who can join

Age: 18 and older, up to 101. Sex: any. Healthy volunteers: not accepted.

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.
• Participants who underwent stem cell transplant (SCT) >100 days for autologous SCT or >180 days for allogeneic SCT before study drug administration and exhibited a full hematological recovery (consistent with the existing inclusion criteria requirements and without PRBC or platelet transfusions within 2 weeks of C1D1) prior to relapse 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
• Have adequate bone marrow function, as determined by all the following:
• Absolute neutrophil count (ANC) ≥1,000/mm³
• Platelet count ≥50,000 mm³
• Hemoglobin ≥8g/dL
• Have adequate kidney function, creatinine clearance (CLcr) to be ≥50mL/min either measured or assessed by using the Cockcroft-Gault formula.
• a. At the investigator's discretion, the eGFR result ≤50 mL/min may be verified by measurement of CLcr based on the 24-hour urine collection. Participants with CLcr ≥50 mL/min will be eligible irrespective of the eGFR result.
• Have adequate hepatic function, as determined by:
• Total bilirubin ≤1.5 x upper limit normal (ULN), or direct bilirubin ≤1.5 x ULN for participants with elevated total bilirubin secondary to Gilbert's Syndrome) and

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.
• Arterial thrombosis or pulmonary embolism within ≤3 months before the start of treatment.
• Myocardial infarction or stroke within ≤3 months before the start of treatment.
• Pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade ≥2), non malignant pleural effusion (CTCAE Grade ≥2) or malignant pleural effusion (CTCAE Grade ≥3).
• Congestive heart failure New York Heart Association (NYHA) Class III or IV at screening or left ventricular ejection fraction (LVEF) <45%, assessed by Echo or multiple-gated acquisition (MUGA) scan within 1 month before starting study treatment. (inclusion of participants with LVEF between 40%-45% should be discussed and approved by the sponsor). Echo or MUGA scan performed within 6 months before screening and at least 28 days after the last cancer therapy is acceptable provided the participant has not received any potential cardiotoxic agents since then.
• Cardiac arrhythmia requiring anti-arrhythmic therapy at Screening. Participants receiving digoxin, calcium channel blockers, or beta-adrenergic blockers are eligible at the investigator's discretion after consultation with medical monitor if the dose has been stable for ≥2 weeks before the start of treatment with MT-3724. Participants with sinus arrhythmia and infrequent premature ventricular contractions are eligible at the investigator's discretion.
• QT interval corrected according to Fridericia's formula (QTcF) >480 ms, determined as the average from three QTcF values on the triplicate electrocardiogram (ECG) obtained at Screening.
• Current evidence of uncontrolled HIV, HBV or 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:
• Participants with HIV and an undetectable viral load and CD4+ T-cells counts ≥350 cells/microliter may be enrolled, but must be taking appropriate opportunistic infection prophylaxis, if clinically relevant.
• 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.
• Participants with positive HCV serology are eligible if quantitative PCR for plasma HCV RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.

Where it is running

• Innovative Clinical Research Institute — Whittier, California, United States
• Boca Raton Clinical Research — Plantation, Florida, United States
• Rush University — Chicago, Illinois, United States
• University of Maryland — Baltimore, Maryland, United States
• University of Texas Southwestern — Dallas, Texas, United States

Full record on ClinicalTrials.gov

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