Zanubrutinib and Tafasitamab in Mantle Cell Lymphoma

NCT06029309 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20221346
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

  4 weeks

• 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.

  Up to 48 weeks

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  Up to 48 weeks

• Progression-free Survival (PFS)

  Up to 48 months

• Overall Survival (OS)

  Up to 48 months

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

  Up to 27 months

• Phase 2: Duration of Response (DOR)

  Up to 48 months

Study Arms (2)

Zanu-Tafa Phase 1 Group

EXPERIMENTAL

Participants in this group will receive combination therapy of Zanubrutinib (Zanu) and Tafasitamab (Tafa) for up to 24 cycles, followed by maintenance therapy with Zanubrutinib until progression. Each cycle is 28 days in length. Combination therapy will be administered via induction phases as follows: 1. Early induction - cycles 1 to 3 (12 weeks) 2. Late induction - cycles 4 to 12 (36 weeks) 3. Extended induction - cycles 13-24 (48 weeks) Subsequent maintenance Zanu therapy may last up to 2 years. Total study participation is up to four (4) years.

Drug: Zanubrutinib; Drug: Tafasitamab

Zanu-Tafa Phase 2 Group

EXPERIMENTAL

Participants in this group will receive the combination therapy of Zanubrutinib (Zanu) at the recommended phase 2 dose (RP2D) determined during Phase 1, and Tafasitamab at standard doses, followed by maintenance therapy with Zanubrutinib until progression.. Combination therapy will be administered via induction phases as follows: 1. Early induction - cycles 1 to 3 (12 weeks) 2. Late induction - cycles 4 to 12 (36 weeks) 3. Extended induction - cycles 13-24 (48 weeks) Subsequent maintenance Zanu therapy may last up to 2 years. Total study participation is up to four (4) years.

Drug: Zanubrutinib; Drug: Tafasitamab

Interventions

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.

Zanu-Tafa Phase 1 Group; Zanu-Tafa Phase 2 Group

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

Zanu-Tafa Phase 1 Group; Zanu-Tafa Phase 2 Group

Eligibility Criteria

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

You may qualify if:

• 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
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Life expectancy of greater than 4 months.
• Willingness to avoid pregnancy or fathering children during the study and for at least 90 days after the last dose of the study drug.
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count \>1,000/mm3 independent of growth factor support within 7 days of study entry (\>700/mm3 if lymphoma involvement of the bone marrow or spleen)
• Platelets \>70,000/mm3 independent of transfusion support within 7 days of study entry (\>50,000/mm3 independent of transfusion support within 7 days of study entry if lymphoma involvement of the bone marrow or spleen)
• Hemoglobin \>9 g/dL or \>8 g/dL in case of bone marrow involvement by lymphoma independent of transfusion support within 7 days of study entry.
• Total bilirubin \< 1.5 x within normal institutional limits (unless known history of Gilbert's disease or up to 3 x upper limit of normal (ULN) if due to lymphoma involvement of liver)
• Gamma-Glutamyl Transpeptidase (GGT)/Aspartate transaminase (AST, SGOT)/Alanine transaminase (ALT, SGPT) ≤ 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits, or creatinine clearance ≥ 40 mL/min (as estimated by the Cockcroft-Gault equation) for patients with creatinine levels above institutional normal (creatinine clearance ≥ 30 mL/min as estimated by the Cockcroft-Gault equation if due to lymphoma).
• \. Relapsed MCL patients with at least 1 but no more than 3 lines of therapy, regardless of previous Bruton Tyrosine Kinase (BTK) inhibitor exposure

You may not qualify if:

• 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
• Prior or concurrent malignancies with exception of surgically cured carcinoma in situ (CIS) of the uterus, carcinoma of the skin without evidence of disease for ≥5 years
• Concurrent malignancy requiring active therapy
• Known seropositive and requiring anti-viral therapy for human immunodeficiency virus
• Breastfeeding or pregnant women
• Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody will need a polymerase chain reaction (PCR) below cutoff value prior to enrollment. (PCR positive patients will be excluded). Hepatitis C antibody positive patients are eligible if PCR is negative. Hepatitis B core antibody (+) patients without evidence of HBsAg or Hep B PCR (+) are eligible with appropriate Hepatitis B reactivation prophylaxis
• Ongoing treatment with medications that are moderate or strong cytochrome P (CYP) 450, family 3, subfamily A (CYP3A) inhibitors, or strong CYP3A inducers that cannot be safely substituted. For patients with ongoing treatment with these medications that can be safely substituted, minimum washout period should be 7 days or five half-lives, whichever is shorter.
• History of allogenic hematopoietic stem cell transplantation prior to enrollment
• Active systemic infection (including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test) or other Active infection including infections requiring oral or intravenous antimicrobial therapy.
• Administration of live vaccine within 28 days prior to start of study treatment
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the patient's safety or put the study at risk.
• Unable to swallow capsules, or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

Sponsors & Collaborators

• Alvaro Alencar, MD: lead
• BeiGene: collaborator
• Incyte Corporation: collaborator
• MorphoSys AG: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

zanubrutinib; tafasitamab

Condition Hierarchy (Ancestors)

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

Study Officials

• Alvaro Alencar, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alvaro Alencar, MD

CONTACT

(305) 243-4372; aalencar@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Clinical

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: September 8, 2023
• Study Start: May 3, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2032
• Last Updated: October 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)