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Zanubrutinib and Tafasitamab in Mantle Cell Lymphoma

ConditionMantle Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAlvaro Alencar, MD

About this trial

The main purpose of this study to find the ideal dose for the combination treatment of Zanubrutinib and Tafasitamab in patients with mantle cell lymphoma. Another purpose is to assess how well the combination treatment works in patients with the study disease.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Men and women ≥ 18 years of age

Patients must have histologic confirmation of mantle cell lymphoma (MCL) defined by the World Health Organization (WHO) classification

Baseline PET/CT scans must demonstrate fluorodeoxyglucose (FDG) avid lesions compatible with CT defined anatomical tumor sites. Patients should have at least one measurable site of disease per Lugano classification

Patient should have indication according to primary investigator for treatment initiation

Disqualifiers

Patients receiving any other investigational agents

Patients with known central nervous system involvement of lymphoma

Uncontrolled intercurrent illness such as: clinically significant active cardiovascular disease such as uncontrolled or symptomatic arrhythmia, uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) Class III-IV, history of myocardial infarction within 6 months of screening, stroke in last 6 months, liver cirrhosis, autoimmune disorder requiring immunosuppression or long-term corticosteroids (>10 mg daily prednisone equivalent), or any other serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form

QT interval corrected with Fridericia's formula (QTcF) > 450 msec or other significant ECG abnormalities including second-degree atrioventricular block Type II, or third-degree atrioventricular block

Trial design

Design model

Sequential

Treatments tested in this trial

  • Zanubrutinib

    Drug

    Participants will be administered Zanubrutinib orally (PO) via capsules daily during each 28-day cycle at the following dose levels: * Phase 1 Dose Level 1: 320 mg * Phase 1 Dose Level -1: 240 mg * Phase 2: Recommended dose determined in Phase 1.

  • Tafasitamab

    Drug

    Participants will be administered a 12 mg/kg dose of Tafasitamab intravenously (IV) during each 28-day cycle as follows: * Early Induction - Cycle 1: Days 1, 4, 8, 15, and 22 * Early Induction - Cycles 2 and 3: Days 1, 8, 15 and 22 * Late Induction - Cycles 4 through 12: Days 1 and 15

Treatment groups

27 Participants
are divided into 2 treatment groups
Group A: Zanu-Tafa Phase 1 GroupExperimental treatment 2 interventions
Group B: Zanu-Tafa Phase 2 GroupExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Phase 1: Recommended Phase 2 Dose (RP2D) of Zanubrutinib

Determination of the RP2D of Zanubrutinib, when used in combination with Tafasitamab, based on evaluation of dose limiting toxicity (DLT) in participants during the Phase 1 part of the study. DLT will be defined as the occurrence of specified adverse events (AEs) at least possibly related to the study therapy during the DLT review period.

Time frame
4 weeks
2

Phase 2: Rate of Complete Response (CR) to Zanubrutinib at RP2D

The complete response (CR) rate among study participants in Phase 2 to Zanubrutinib at the RP2D in combination with Tafasitamab will be assessed. Response will be assessed using positron emission tomography (PET)/computerized tomography (CT) according to the Lugano 2014 criteria. CR will be defined by a Deauville score of less than or equal to (≤) 3.

Time frame
Up to 48 weeks

Secondary outcomes

1

Overall Response Rate (ORR)

The overall response rate (ORR) in study participants will be assessed. ORR will be defined at the percentage of participants achieving complete response (CR) or partial response to study therapy at at the end of early (cycles 1-3) and late induction (cycles 4-12). Response to treatment will be assessed using PET/CT according to Lugano 2014 criteria after weeks 12 and 48 of treatment. CR will be defined by a Deauville score of ≤ 3, and PR by a Deauville score of 4 or 5 with reduced uptake from baseline.

Time frame
Up to 48 weeks
2

Progression-free Survival (PFS)

Progression-free survival among study participants will be assessed during treatment and clinical follow-up. PFS is defined as the time from start of treatment until disease progression or death.

Time frame
Up to 48 months
3

Overall Survival (OS)

Overall survival (OS) among study participants will be assessed during treatment and clinical follow-up. OS is defined from start of treatment until death from any cause.

Time frame
Up to 48 months
4

Number of Participants Experiencing Treatment-related Adverse Events (AEs) and Serious Adverse Events (SAEs)

The dosing, safety, and feasibility of combination of Zanubrutinib and Tafasitamab will be assessed and reported among study participants in Phase 1 as the number of participants experiencing treatment-related toxicity after start of study therapy, including treatment-related adverse events (AEs) and serious adverse events (SAEs). AEs and SAEs will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion.

Time frame
Up to 27 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Alvaro Alencar, MD

Lead sponsor

University of Miami

Sponsor institution

Incyte Corporation

Collaborator

BeOne Medicines

Collaborator

Source ClinicalTrials.gov
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