A Phase 1/2 Study of Zanubrutinib and Tafasitamab in Mantle Cell Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- Zanubrutinib
- Conditions
- Mantle Cell Lymphoma
- Sponsor
- Alvaro Alencar, MD
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Phase 1: Recommended Phase 2 Dose (RP2D) of Zanubrutinib
- Status
- Recruiting
- Last Updated
- 6 months ago
Overview
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.
Investigators
Alvaro Alencar, MD
Associate Professor of Clinical
University of Miami
Eligibility Criteria
Inclusion Criteria
- •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)
Exclusion Criteria
- Not provided
Arms & Interventions
Zanu-Tafa Phase 1 Group
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.
Intervention: Zanubrutinib
Zanu-Tafa Phase 1 Group
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.
Intervention: Tafasitamab
Zanu-Tafa Phase 2 Group
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.
Intervention: Zanubrutinib
Zanu-Tafa Phase 2 Group
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.
Intervention: Tafasitamab
Outcomes
Primary Outcomes
Phase 1: Recommended Phase 2 Dose (RP2D) of Zanubrutinib
Time Frame: 4 weeks
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.
Phase 2: Rate of Complete Response (CR) to Zanubrutinib at RP2D
Time Frame: Up to 48 weeks
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.
Secondary Outcomes
- Progression-free Survival (PFS)(Up to 48 months)
- Overall Response Rate (ORR)(Up to 48 weeks)
- 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)
- Phase 2: Time to Next Treatment (TTNT)(Up to 24 months)