Randomized Phase II Study of the Addition of Targeted Therapeutic Agents to Tafasitamab-Based Therapy in Non-Transplant-Eligible Patients With Relapsed/Refractory Large B-Cell Lymphoma

Status: Recruiting
Location: See all (104) locations...
Intervention Type: Other, Procedure, Drug, Biological
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

This phase 2 trial studies the side effects and best dose of tazemetostat and zanubrutinib in combination with tafasitamab and lenalidomide, and to see how well these combinations work in treating patients with large B-cell lymphoma that returned or did not respond to earlier treatment. Tazemetostat is in a class of medications called EZH2 inhibitors. It helps to stop the spread of cancer cells. Zanubrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells. tafasitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Lenalidomide is in a class of medications called immunomodulatory agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow. The addition of tazemetostat or zanubrutinib to tafasitamab and lenalidomide may be able to shrink the cancer or extend the time without cancer symptoms coming back.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Participants must have:

‣ Histologically confirmed relapsed/refractory LBCL as outlined by the World Health Organization (WHO) guidelines

⁃ Follicular lymphoma, grade 3B

⁃ Transformed lymphoma

⁃ High grade B-cell lymphoma with or without MYC, BCL2 and/or BCL6 rearrangements

• Participants must have staging imaging performed within 28 days prior to registration, as follows. Positron emission tomography (PET)-computed tomography (CT) baseline scans are strongly preferred; diagnostic quality magnetic resonance imaging (MRI), contrast-enhanced CT, or contrast-enhanced MRI scans are also acceptable if PET-CT is not feasible at baseline. Note: PET-CT will be required at end of treatment (EOT) and progression for response assessment. All measurable lesions (longest diameter \>= 1.5 cm) must be assessed within 28 days prior to registration. Tests to assess non-measurable disease must be performed within 28 days prior to registration. All disease must be documented on the Baseline Tumor Assessment Form.

• Participants must have cell of origin (COO) determination of germinal center (GC)(GCB or non-GC GCB) of LBCL based on Hans immunohistochemistry algorithm (CD10, BCL6, MUM1) as noted on pathology report.

• Participants must have had 1-5 prior systemic treatment regimens including one systemic multiagent regimen for aggressive lymphoma

• Participants who have received prior systemic therapy must have completed their last treatment prior to registration. Participants must have recovered from previous therapy

• Steroid use for the control of non-Hodgkin lymphoma symptoms is allowable, but must be discontinued prior to Cycle 1, Day 1

• Participant must be \>= 18 years old

• Participant must have Zubrod Performance Status of 0-3

• Participant must have a complete medical history and physical exam within 28 days prior to registration

• Absolute neutrophil count \>= 1.0 x 10\^3/uL (within 28 days prior to registration)

‣ If there is documented lymphomatous involvement of the bone marrow as assessed by bone marrow biopsy within 90 days prior to registration, participants must have: Absolute neutrophil count (ANC) \>= 0.75 x 10\^3/uL

• Platelets \>= 75 x 10\^3/uL (within 28 days prior to registration)

‣ If there is documented lymphomatous involvement of the bone marrow as assessed by bone marrow biopsy within 90 days prior to registration, participants must have: Platelets \>= 50 x 10\^3/uL

• Aspartate aminotransferase (AST) =\< 3 x institutional upper limit of normal (IULN), alanine aminotransferase (ALT) =\< 3 x IULN (within 28 days prior to registration) unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver.

‣ Participants with lymphomatous involvement of the liver must have AST =\< 5 x IULN, ALT =\< 5 x IULN

• Total bilirubin =\< 1.5 x IULN (within 28 days prior to registration) unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver.

‣ Participants with lymphomatous involvement of the liver must have total bilirubin =\< 5 x IULN

• Participants must have a calculated creatinine clearance \>= 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration

• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better

• Participants must have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia

• Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at randomization and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration

• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on the most recent test results obtained within the last year and received suppressive therapy

• Participants with a history of hepatitis C virus (HCV) infection must have an undetectable viral load. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 28 days prior to registration

• Participants must be able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the stomach or bowels

• Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System

• Participants who can complete the FACT-Lym and PRO-CTCAE forms in English or Spanish must agree to participate in the patient-reported outcome study

• Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.

‣ For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and central institutional review board (CIRB) regulations.

Locations
United States
Arizona
Banner University Medical Center - Tucson
RECRUITING
Tucson
University of Arizona Cancer Center-North Campus
RECRUITING
Tucson
California
Tower Cancer Research Foundation
RECRUITING
Beverly Hills
City of Hope Comprehensive Cancer Center
RECRUITING
Duarte
City of Hope Seacliff
RECRUITING
Huntington Beach
City of Hope Antelope Valley
RECRUITING
Lancaster
City of Hope at Long Beach Elm
RECRUITING
Long Beach
Cedars Sinai Medical Center
RECRUITING
Los Angeles
City of Hope Newport Beach
RECRUITING
Newport Beach
City of Hope South Pasadena
RECRUITING
South Pasadena
City of Hope South Bay
RECRUITING
Torrance
City of Hope Upland
RECRUITING
Upland
Florida
Holy Cross Hospital
RECRUITING
Fort Lauderdale
Mount Sinai Medical Center
SUSPENDED
Miami Beach
Iowa
UI Health Care Mission Cancer and Blood - Ankeny Clinic
SUSPENDED
Ankeny
Mercy Hospital
RECRUITING
Cedar Rapids
Oncology Associates at Mercy Medical Center
RECRUITING
Cedar Rapids
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
SUSPENDED
Clive
Mercy Medical Center - Des Moines
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Laurel Clinic
SUSPENDED
Des Moines
Illinois
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
University of Illinois
RECRUITING
Chicago
Carle at The Riverfront
RECRUITING
Danville
Carle Physician Group-Effingham
RECRUITING
Effingham
Carle Physician Group-Mattoon/Charleston
RECRUITING
Mattoon
UC Comprehensive Cancer Center at Silver Cross
RECRUITING
New Lenox
University of Chicago Medicine-Orland Park
RECRUITING
Orland Park
Memorial Hospital East
RECRUITING
Shiloh
Carle Cancer Center
RECRUITING
Urbana
Indiana
Northwest Cancer Center - Main Campus
RECRUITING
Crown Point
Northwest Oncology LLC
RECRUITING
Dyer
Northwest Cancer Center - Hobart
RECRUITING
Hobart
Saint Mary Medical Center
RECRUITING
Hobart
Saint Catherine Hospital
RECRUITING
Indianapolis
The Community Hospital
RECRUITING
Munster
Women's Diagnostic Center - Munster
RECRUITING
Munster
Northwest Cancer Center - Valparaiso
RECRUITING
Valparaiso
Michigan
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
RECRUITING
Ann Arbor
Trinity Health IHA Medical Group Hematology Oncology - Brighton
RECRUITING
Brighton
Trinity Health Medical Center - Brighton
RECRUITING
Brighton
Trinity Health IHA Medical Group Hematology Oncology - Canton
RECRUITING
Canton
Trinity Health Medical Center - Canton
RECRUITING
Canton
Chelsea Hospital
RECRUITING
Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
RECRUITING
Chelsea
Cancer Hematology Centers - Flint
RECRUITING
Flint
Genesee Hematology Oncology PC
SUSPENDED
Flint
Genesys Hurley Cancer Institute
RECRUITING
Flint
Hurley Medical Center
RECRUITING
Flint
University of Michigan Health - Sparrow Lansing
RECRUITING
Lansing
Trinity Health Saint Mary Mercy Livonia Hospital
RECRUITING
Livonia
Trinity Health Saint Joseph Mercy Oakland Hospital
RECRUITING
Pontiac
Huron Gastroenterology PC
RECRUITING
Ypsilanti
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
RECRUITING
Ypsilanti
Minnesota
Essentia Health - Deer River Clinic
RECRUITING
Deer River
Essentia Health Cancer Center
RECRUITING
Duluth
Essentia Health Hibbing Clinic
RECRUITING
Hibbing
Essentia Health Sandstone
RECRUITING
Sandstone
Essentia Health Virginia Clinic
RECRUITING
Virginia
Missouri
Siteman Cancer Center at Saint Peters Hospital
RECRUITING
City Of Saint Peters
Siteman Cancer Center at West County Hospital
RECRUITING
Creve Coeur
Siteman Cancer Center at Christian Hospital
RECRUITING
St Louis
Siteman Cancer Center-South County
RECRUITING
St Louis
Washington University School of Medicine
RECRUITING
St Louis
Mississippi
University of Mississippi Medical Center
RECRUITING
Jackson
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITING
New York
University of Rochester
RECRUITING
Rochester
Wilmot Cancer Institute at Webster
RECRUITING
Webster
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Oregon
Providence Newberg Medical Center
RECRUITING
Newberg
Providence Willamette Falls Medical Center
RECRUITING
Oregon City
Providence Portland Medical Center
RECRUITING
Portland
Providence Saint Vincent Medical Center
RECRUITING
Portland
South Carolina
Medical University of South Carolina
RECRUITING
Charleston
Texas
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
RECRUITING
Houston
Ben Taub General Hospital
RECRUITING
Houston
University of Texas Health Science Center at San Antonio
RECRUITING
San Antonio
Utah
Huntsman Cancer Institute/University of Utah
RECRUITING
Salt Lake City
Virginia
VCU Massey Cancer Center at Stony Point
RECRUITING
Richmond
VCU Massey Comprehensive Cancer Center
RECRUITING
Richmond
Wisconsin
ThedaCare Regional Cancer Center
RECRUITING
Appleton
Duluth Clinic Ashland
RECRUITING
Ashland
Aurora Cancer Care-Southern Lakes VLCC
RECRUITING
Burlington
Marshfield Medical Center-EC Cancer Center
RECRUITING
Eau Claire
Aurora Health Care Germantown Health Center
RECRUITING
Germantown
Aurora Cancer Care-Grafton
RECRUITING
Grafton
Aurora BayCare Medical Center
RECRUITING
Green Bay
Aurora Cancer Care-Kenosha South
RECRUITING
Kenosha
Gundersen Lutheran Medical Center
RECRUITING
La Crosse
Aurora Bay Area Medical Group-Marinette
RECRUITING
Marinette
Marshfield Medical Center-Marshfield
RECRUITING
Marshfield
Aurora Cancer Care-Milwaukee
RECRUITING
Milwaukee
Aurora Saint Luke's Medical Center
RECRUITING
Milwaukee
Aurora Sinai Medical Center
RECRUITING
Milwaukee
Marshfield Medical Center - Minocqua
RECRUITING
Minocqua
Vince Lombardi Cancer Clinic - Oshkosh
RECRUITING
Oshkosh
Aurora Cancer Care-Racine
RECRUITING
Racine
Marshfield Medical Center-Rice Lake
RECRUITING
Rice Lake
Vince Lombardi Cancer Clinic-Sheboygan
RECRUITING
Sheboygan
Marshfield Medical Center-River Region at Stevens Point
RECRUITING
Stevens Point
Aurora Medical Center in Summit
RECRUITING
Summit
Vince Lombardi Cancer Clinic-Two Rivers
RECRUITING
Two Rivers
Aurora Cancer Care-Milwaukee West
RECRUITING
Wauwatosa
Aurora West Allis Medical Center
RECRUITING
West Allis
Marshfield Medical Center - Weston
RECRUITING
Weston
Contact Information
Primary
Katarina Gasic
kgasic@swog.org
210-677-8808
Backup
Crystal Miwa
cmiwa@swog.org
210-677-8808
Time Frame
Start Date: 2023-09-26
Estimated Completion Date: 2029-01
Participants
Target number of participants: 227
Treatments
Experimental: Part I, Arm I (tafasitamab, lenalidomide, tazemetostat)
Patients receive tafasitamab IV, lenalidomide PO, and tazemetostat PO on study. Patients also undergo PET/CT and CT or MRI scans throughout the trial. Patients also have the option to undergo collection of blood samples during screening and on study.
Experimental: Part I, Arm III (tafasitamab, lenalidomide, zanubrutinib)
Patients receive tafasitamab IV, lenalidomide PO, and zanubrutinib PO on study. Patients also undergo PET/CT and CT or MRI scans throughout the trial. Patients also have the option to undergo collection of blood samples during screening and on study.
Experimental: Part II, Arm I (tafasitamab, lenalidomide, tazemetostat)
Patients receive tafasitamab IV, lenalidomide PO, and tazemetostat PO on study. Patients also undergo PET/CT and CT or MRI scans throughout the trial. Patients also have the option to undergo collection of blood samples during screening and on study.
Active_comparator: Part II, Arm II (tafasitamab, lenalidomide)
Patients receive tafasitamab IV and lenalidomide PO on study. Patients also undergo PET/CT and CT or MRI scans throughout the trial. Patients also have the option to undergo collection of blood samples during screening and on study.
Experimental: Part II, Arm III (tafasitamab, lenalidomide, zanubrutinib)
Patients receive tafasitamab IV, lenalidomide PO, and zanubrutinib PO on study. Patients also undergo PET/CT and CT or MRI scans throughout the trial. Patients also have the option to undergo collection of blood samples during screening and on study.
Sponsors
Collaborators: Ipsen, BeiGene, Incyte Corporation, National Cancer Institute (NCI)
Leads: SWOG Cancer Research Network

This content was sourced from clinicaltrials.gov

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