Trial record 5 of 31 for:
Recruiting, Not yet recruiting Studies | swog [Lead]
Study Adding Drugs to Usual Treatment for Large B-Cell Lymphoma That Returned or Did Not Respond to Treatment
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT05890352 |
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Recruitment Status :
Recruiting
First Posted : June 6, 2023
Last Update Posted : October 5, 2023
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Sponsor:
SWOG Cancer Research Network
Collaborators:
National Cancer Institute (NCI)
BeiGene
Ipsen
Incyte Corporation
Information provided by (Responsible Party):
SWOG Cancer Research Network
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Grade 3b Follicular Lymphoma High Grade B-Cell Lymphoma High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements Recurrent Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma Transformed Non-Hodgkin Lymphoma | Procedure: Biospecimen Collection Procedure: Computed Tomography Drug: Lenalidomide Procedure: Magnetic Resonance Imaging Procedure: Positron Emission Tomography Other: Quality-of-Life Assessment Other: Questionnaire Administration Biological: Tafasitamab Drug: Tazemetostat Drug: Zanubrutinib | Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 227 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | September 26, 2023 |
| Estimated Primary Completion Date : | December 31, 2026 |
| Estimated Study Completion Date : | January 2029 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Lymphoma
| Arm | Intervention/treatment |
|---|---|
|
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.
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Procedure: Biospecimen Collection
Undergo optional collection of blood
Other Names:
Procedure: Computed Tomography Undergo PET/CT and CT
Other Names:
Drug: Lenalidomide Given PO
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Procedure: Positron Emission Tomography Undergo PET/CT
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Biological: Tafasitamab Given IV
Other Names:
Drug: Tazemetostat Given PO
Other Names:
|
|
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.
|
Procedure: Biospecimen Collection
Undergo optional collection of blood
Other Names:
Procedure: Computed Tomography Undergo PET/CT and CT
Other Names:
Drug: Lenalidomide Given PO
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Procedure: Positron Emission Tomography Undergo PET/CT
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Biological: Tafasitamab Given IV
Other Names:
Drug: Zanubrutinib Given PO
Other Names:
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|
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.
|
Procedure: Biospecimen Collection
Undergo optional collection of blood
Other Names:
Procedure: Computed Tomography Undergo PET/CT and CT
Other Names:
Drug: Lenalidomide Given PO
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Procedure: Positron Emission Tomography Undergo PET/CT
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Biological: Tafasitamab Given IV
Other Names:
Drug: Tazemetostat Given PO
Other Names:
|
|
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.
|
Procedure: Biospecimen Collection
Undergo optional collection of blood
Other Names:
Procedure: Computed Tomography Undergo PET/CT and CT
Other Names:
Drug: Lenalidomide Given PO
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Procedure: Positron Emission Tomography Undergo PET/CT
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Biological: Tafasitamab Given IV
Other Names:
|
|
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.
|
Procedure: Biospecimen Collection
Undergo optional collection of blood
Other Names:
Procedure: Computed Tomography Undergo PET/CT and CT
Other Names:
Drug: Lenalidomide Given PO
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Procedure: Positron Emission Tomography Undergo PET/CT
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Biological: Tafasitamab Given IV
Other Names:
Drug: Zanubrutinib Given PO
Other Names:
|
Primary Outcome Measures :
- Progression-free survival (PFS) [ Time Frame: From date of randomization to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause, assessed up to 3 years ]Will be compared between participants randomized to control Arm 2 (tafasitamab + lenalidomide) versus (vs) experimental Arm 1 (tafasitamab + lenalidomide + tazemetostat), AND control Arm 2 vs experimental Arm 3 (tafasitamab + lenalidomide + zanubrutinib), respectively.
- Trial Outcome Index (TOI) score from the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) (Patient Reported Outcome [PRO] Study) [ Time Frame: Baseline up to 3 months after randomization ]Will compare the trial outcome index (TOI) score between each experimental arm (Arm 1 and Arm 3) to the control arm (Arm 2). The TOI score is composed of the Physical Well-Being, Functional Well-Being, and lymphoma-specific subscale scores. The scores range from 0-116, with higher scores indicating a higher quality of life.
Secondary Outcome Measures :
- Hazard ratio for PFS in the germinal center B-cell (GCB) subgroup [ Time Frame: Up to 3 years ]Will calculate the 80% confidence interval (CI) for the Cox regression time-to-event estimate of the hazard ratio associated with addition of tazemetostat to tafasitamab+lenalidomide combination (Arm 2 vs Arm 1) in the GCB subgroup. If the confidence interval excludes 1, then 80% CI will be calculated for the non-GCB group.
- Hazard ratio for PFS in the non-GCB subgroup [ Time Frame: Up to 3 years ]Will calculate the 80% CI for the hazard ratio associated with addition of zanubrutinib to tafasitamab+lenalidomide combination (Arm 2 vs Arm 3) in the non-GCB subgroup. If the confidence interval excludes 1, then 80% CI will be calculated for the GCB group.
- PFS [ Time Frame: From date of randomization to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause, assessed up to 3 years ]Will estimate in GCB and non-GCB large B-cell lymphoma (LBCL) for each treatment. Will be estimated using the method of Kaplan-Meier and 80% confidence interval will be calculated.
- Overall response rate (ORR) [ Time Frame: Up to 3 years ]Will estimate in GCB and non-GCB LBCL for each treatment. Will be estimated using the method of Kaplan-Meier and 80% confidence interval will be calculated.
- Complete response (CR) rate [ Time Frame: Up to 3 years ]Will estimate in GCB and non-GCB LBCL for each treatment. Will be estimated using the method of Kaplan-Meier and 80% confidence interval will be calculated.
- Partial response (PR) rate [ Time Frame: Up to 3 years ]Will estimate in GCB and non-GCB LBCL for each treatment. Will be estimated using the method of Kaplan-Meier and 80% confidence interval will be calculated.
- Duration of response (DOR) [ Time Frame: From date of first documentation of response to treatment (CR, PR) to date of first documentation of progression, or death due to any cause among patients who achieve a response (CR or PR), assessed up to 3 years ]Will estimate in GCB and non-GCB LBCL for each treatment. Will be estimated using the method of Kaplan-Meier and 80% confidence interval will be calculated.
- Event free survival (EFS) [ Time Frame: From date of randomization to date of first occurrence of EFS event, assessed up to 3 years ]Will estimate in GCB and non-GCB LBCL for each treatment. Will be estimated using the method of Kaplan-Meier and 80% confidence interval will be calculated.
- Overall survival (OS) [ Time Frame: From date of randomization to date of death due to any cause, assessed up to 3 years ]Will estimate in GCB and non-GCB LBCL for each treatment. Will be estimated using the method of Kaplan-Meier and 80% confidence interval will be calculated.
- Incidence of adverse events [ Time Frame: Up to 3 years ]Will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Eligible participants receiving at least one dose of drug will be included in the assessment of adverse events by treatment arms. The maximum Grade for each toxicity will be recorded for each participant, and frequency tables will be reviewed to determine toxicity patterns. With 60 eligible participants in each arm, any toxicity occurring with at least 5% probability is likely to be seen at least once (95% chance). Toxicity rates in each arm can be estimated to within at least +/- 13% with 95% confidence.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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
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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
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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
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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
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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
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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.
Exclusion Criteria:
- Participants must not have active lymphomatous involvement of the central nervous system (CNS) because the treatments used in this study are not effective to sufficiently penetrate the blood brain barrier
- Participants must not have known abnormalities associated with myelodysplastic syndrome (MDS) (e.g., del 5q, chr 7 abn) and myeloproliferative neoplasms (MPN) (e.g., JAK2 V617F) observed in cytogenetic testing and deoxyribonucleic acid (DNA) sequencing. Testing is not required for eligibility determination
- Participants must not have a known prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute leukemia (T-ALL). Testing is not required for eligibility determination
- Participants must not be a candidate based on investigator assessment to receive autologous stem cell transplant (ASCT) or must have declined ASCT. Participants who had disease progression after stem cell transplant or cellular therapy (such as chimeric antigen receptor (CAR) T-cell) are eligible
- Participants must not have received prior treatment with tafasitamab and/or lenalidomide
- Participants must not have had prior BTK inhibitor or tazemetostat
- Participants must not have any known allergy or reaction to any component of tafasitamab, lenalidomide, tazemetostat or zanubrutinib
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Participants must not be receiving direct vitamin K inhibitors or strong or moderate CYP3A inhibitors or inducers at the date of registration
- Notes: Because the list of these agents is constantly changing, it is important to regularly consult a frequently updated medical reference
- Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
- Participants must not be pregnant or nursing and must follow the guidelines according to the lenalidomide Risk Evaluation and Mitigation Strategies (REMS) program. The effects of tazemetostat, zanubrutinib, lenalidomide and tafasitamab, and the combination of these drugs have not been studied on the developing human fetus are the effects are unknown. Individuals who are of reproductive potential must have agreed to use a highly effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential". In addition to routine contraceptive methods, "acceptable contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05890352
Contacts
| Contact: Katarina Gasic | 210-677-8808 | kgasic@swog.org | |
| Contact: Crystal Miwa | 210-677-8808 | cmiwa@swog.org |
Locations
| United States, Michigan | |
| Saint Joseph Mercy Hospital | Recruiting |
| Ann Arbor, Michigan, United States, 48106 | |
| Contact: Site Public Contact 734-712-7251 MCRCwebsitecontactform@stjoeshealth.org | |
| Principal Investigator: Tareq Al Baghdadi | |
| Saint Joseph Mercy Brighton | Recruiting |
| Brighton, Michigan, United States, 48114 | |
| Contact: Site Public Contact 734-712-7251 MCRCwebsitecontactform@stjoeshealth.org | |
| Principal Investigator: Tareq Al Baghdadi | |
| Trinity Health IHA Medical Group Hematology Oncology - Brighton | Recruiting |
| Brighton, Michigan, United States, 48114 | |
| Contact: Site Public Contact 734-712-7251 MCRCwebsitecontactform@stjoeshealth.org | |
| Principal Investigator: Tareq Al Baghdadi | |
| Saint Joseph Mercy Canton | Recruiting |
| Canton, Michigan, United States, 48188 | |
| Contact: Site Public Contact 734-712-7251 MCRCwebsitecontactform@stjoeshealth.org | |
| Principal Investigator: Tareq Al Baghdadi | |
| Trinity Health IHA Medical Group Hematology Oncology - Canton | Recruiting |
| Canton, Michigan, United States, 48188 | |
| Contact: Site Public Contact 734-712-7251 MCRCwebsitecontactform@stjoeshealth.org | |
| Principal Investigator: Tareq Al Baghdadi | |
| Saint Joseph Mercy Chelsea | Recruiting |
| Chelsea, Michigan, United States, 48118 | |
| Contact: Site Public Contact 734-712-7251 MCRCwebsitecontactform@stjoeshealth.org | |
| Principal Investigator: Tareq Al Baghdadi | |
| Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital | Recruiting |
| Chelsea, Michigan, United States, 48118 | |
| Contact: Site Public Contact 734-712-7251 MCRCwebsitecontactform@stjoeshealth.org | |
| Principal Investigator: Tareq Al Baghdadi | |
| Trinity Health Saint Mary Mercy Livonia Hospital | Recruiting |
| Livonia, Michigan, United States, 48154 | |
| Contact: Site Public Contact 734-712-7251 MCRCwebsitecontactform@stjoeshealth.org | |
| Principal Investigator: Tareq Al Baghdadi | |
| Huron Gastroenterology PC | Recruiting |
| Ypsilanti, Michigan, United States, 48106 | |
| Contact: Site Public Contact 734-712-7251 MCRCwebsitecontactform@stjoeshealth.org | |
| Principal Investigator: Tareq Al Baghdadi | |
| Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus | Recruiting |
| Ypsilanti, Michigan, United States, 48197 | |
| Contact: Site Public Contact 734-712-7251 MCRCwebsitecontactform@stjoeshealth.org | |
| Principal Investigator: Tareq Al Baghdadi | |
| United States, Oregon | |
| SWOG | Recruiting |
| Portland, Oregon, United States, 97239 | |
| Contact: Jennifer E. Amengual 212-305-0591 jea2149@columbia.edu | |
| Principal Investigator: Jennifer E. Amengual | |
Sponsors and Collaborators
SWOG Cancer Research Network
National Cancer Institute (NCI)
BeiGene
Ipsen
Incyte Corporation
Investigators
| Principal Investigator: | Jennifer E Amengual | SWOG Cancer Research Network |
| Responsible Party: | SWOG Cancer Research Network |
| ClinicalTrials.gov Identifier: | NCT05890352 |
| Other Study ID Numbers: |
S2207 NCI-2023-02518 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) S2207 ( Other Identifier: SWOG ) S2207 ( Other Identifier: CTEP ) U10CA180888 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 6, 2023 Key Record Dates |
| Last Update Posted: | October 5, 2023 |
| Last Verified: | October 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
|
Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Lenalidomide Zanubrutinib |
Immunoglobulins Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antineoplastic Agents Tyrosine Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |