Tafasitamab, Retifanlimab, and Rituximab in Combination With Standard Therapy for the Treatment of Diffuse Large B-cell Lymphoma

NCT05455697 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1122398NCI-2022-0452710946
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial tests the safety of tafasitamab, retifanlimab, and rituximab (TRR) as a prephase treatment and in combination with standard therapy consisting off cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or polatuzumab vedotin, cyclophosphamide, doxorubicin, and prednisone (PolaCHP) in patients with untreated diffuse large B-cell lymphoma. Tafasitamab, retifanlimab, and rituximab are monoclonal antibodies. Tafasitamab binds to a protein called CD19, which is found on B-cells (a type of white blood cell) and some types of cancer cells. Rituximab binds to a protein called CD20, which is also found on B-cells and some cancer cells. These monoclonal antibodies may help the immune system kill cancer cells. Immunotherapy with other monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as CHOP and PolaCHP, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving TRR in combination with CHOP or PolaCHP may kill more cancer cells.

Conditions

Diffuse Large B-Cell Lymphoma; Grade 3b Follicular Lymphoma; High Grade B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity rate

  Statistical analysis will entail descriptive statistics of adverse event rates. Will build a Cox proportional hazard model for univariate analysis and multivariable analysis if applicable. Correlative studies may incorporate t-test and linear regression for continuous variables, Chi-squared test and logistic regression for categorical variables will be used, if applicable.

  From treatment start to end of cycle 3 (each cycle is 3 weeks)

Secondary Outcomes (5)

• Overall response rate

  Up to 5 years

• Progression-free survival

  Time from start of trial therapy until relapse or progression, non-protocol re-treatment of lymphoma, or death as a result of any cause, assessed up to 5 years

• Overall survival

  From start of trial therapy to death from any cause, assessed up to 5 years

• Proportion completing prephase

  Up to 5 years

• Relative dose intensity of doxorubicin and cylcophosphamide during combination therapy

  Up to 5 years

Study Arms (1)

Treatment (TRR, CHOP)

EXPERIMENTAL

PREPHASE THERAPY: Patients receive tafasitamab IV over 30 minutes on days 1, 8, and 15 of each cycle, rituximab and hyaluronidase human SC on day 1 of each cycle, and retifanlimab IV over 30 minutes on day 8 of each cycle. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. COMBINATION THERAPY: After completion of prephase therapy or if patients progress during prephase therapy, patients receive tafasitamab IV over 30 minutes, retifanlimab IV over 30 minutes, rituximab and hyaluronidase human SC, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 of each cycle. Patients with an IPI score of 2-5 may receive polatuzumab vedotin IV in place of vincristine at investigator discretion. Patients also receive prednisone PO on days 1-5 of each cycle. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity.

Procedure: Bone Marrow Biopsy; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Biological: Retifanlimab; Biological: Rituximab and Hyaluronidase Human; Biological: Tafasitamab; Drug: Vincristine; Procedure: Bone Marrow Aspiration; Procedure: Multigated Acquisition Scan; Other: Fludeoxyglucose F-18; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Drug: Polatuzumab Vedotin

Interventions

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Treatment (TRR, CHOP)

Cyclophosphamide DRUG

Given IV

Also known as: Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphanum, Cyclostine, Cytophosphane, Cytoxan, Fosfaseron, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (TRR, CHOP)

Doxorubicin DRUG

Given IV

Also known as: 14-Hydroxydaunomycin, 23214-92-8, Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Treatment (TRR, CHOP)

Prednisone DRUG

Given PO

Also known as: Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltra, Econosone, Lisacort, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Predicor, Predicorten, Prednicort, Prednilonga, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Treatment (TRR, CHOP)

Retifanlimab BIOLOGICAL

Given IV

Also known as: 2226345-85-1, INCMGA 0012, INCMGA-0012, INCMGA00012, INCMGA0012, MGA 012, MGA-012, MGA012, Retifanlimab-dlwr, Zynyz

Treatment (TRR, CHOP)

Rituximab and Hyaluronidase Human BIOLOGICAL

Given SC

Also known as: Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human

Treatment (TRR, CHOP)

Tafasitamab BIOLOGICAL

Given IV

Also known as: 1422527-84-1, Immunoglobulin, Anti-(Human Cd19 Antigen) (Human-mus musculus Monoclonal MOR00208 Heavy Chain), Disulfide with Human-mus musculus Monoclonal MOR00208 .Kappa.-chain,, Dimer, Monjuvi, MOR-00208, MOR00208, MOR208, Tafasitamab-cxix, XmAb5574

Treatment (TRR, CHOP)

Vincristine DRUG

Given vincristine

Also known as: 22-Oxovincaleukoblastine, 57-22-7, LEUROCRISTINE, VCR, Vincrystine

Treatment (TRR, CHOP)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (TRR, CHOP)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (TRR, CHOP)

Fludeoxyglucose F-18 OTHER

Undergo FDG-PET/CT

Also known as: 105851-17-0, 18FDG

Treatment (TRR, CHOP)

Positron Emission Tomography PROCEDURE

Undergo FDG-PET

Also known as: Medical Imaging, PET Scan, Positron Emission Tomography Scan

Treatment (TRR, CHOP)

Computed Tomography PROCEDURE

Undergo FDG-CT

Also known as: CAT Scan, Computed Axial Tomography, CT SCAN

Treatment (TRR, CHOP)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection

Treatment (TRR, CHOP)

Polatuzumab Vedotin DRUG

Given IV

Also known as: Antibody-Drug Conjugate DCDS4501A, Polivy

Treatment (TRR, CHOP)

Eligibility Criteria

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

You may qualify if:

• Patients with previously untreated diffuse large B cell lymphoma or grade 3B follicular lymphoma (of any stage). Patients may have de novo DLBCL, and /or any of the following:
• Composite lymphomas, which include both diffuse DLBCL and another histology (most commonly follicular lymphoma) in the same lymph node,
• Transformed lymphoma with DLBCL histology, as long as the patient has not received prior therapy for lymphoma,
• Discordant presentations, such as DLBCL in a lymph node and low-grade lymphoma such as follicular lymphoma in the bone marrow, and
• High grade B-cell lymphoma (including "double hit" lymphomas or high grade B-cell lymphoma-not otherwise specified \[HGBCL-NOS\]) is permitted if the patient is not eligible for or declines intensive therapy
• Be willing and able to provide written informed consent/assent for the trial
• Be \>= 18 years of age on day of signing informed consent
• Have measurable disease, including at least 1 nodal site measuring 1.5 cm or 1 extranodal site measuring 1.0 cm in longest dimension on computed tomography (CT) or fludeoxyglucose F-18-positron emission tomography (FDG-PET)
• Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale (PS)
• Absolute neutrophil count (ANC) \>= 1,000/mcL except in case of marrow infiltration by lymphoma
• Platelets \>= 75,000/mcL except in cases of marrow infiltration by lymphoma
• Serum creatinine clearance (CrCl) must be \>= 30 mL/minute either measured or calculated using a standard Cockcroft and Gault formula
• Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =\< 1.5 x upper limit of normal (ULN) unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma. Patients with Gilbert's syndrome or documented liver involvement by lymphoma may be included if their total bilirubin is =\< 5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN OR =\< 5 x ULN for subjects with liver metastases

You may not qualify if:

• Is currently participating in a study and receiving an investigational agent or is using an investigational device within 4 weeks of the first dose of treatment
• Requires systemic corticosteroids in excess of \> 10 mg/day of prednisone or equivalent. Exceptions:
• Physiologic corticosteroid replacement therapy at doses =\< 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted
• Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate
• Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate
• Brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy) or prephase steroids for disease control, given for up to 7 days, are permitted
• Steroids required for management of immune-related adverse events after initiation of study therapy are permitted
• Has a diagnosis of immunodeficiency
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include resected cutaneous neoplasms, in situ cancer, or any neoplasm not requiring therapy or with a life expectancy exceeding 3 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis
• Has an active infection requiring intravenous antibiotic therapy at the time of start of study therapy
• History of organ transplant, including allogeneic stem cell transplantation
• Has received a live vaccine within 28 days of the planned start of study drug
• Note: Examples of live vaccines include but are not limited to intranasal influenza, measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, BCG, and typhoid vaccine

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Cyclophosphamide; Doxorubicin; Prednisone; Rituximab; Hyaluronoglucosaminidase; tafasitamab; Immunoglobulins; Disulfides; Vincristine; Fluorodeoxyglucose F18; Magnetic Resonance Spectroscopy; X-Rays; polatuzumab vedotin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxyglucose; Deoxy Sugars; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing

Study Officials

• Stephen D. Smith

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen D. Smith

CONTACT

206-606-6546; ssmith50@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2022
• First Posted: July 13, 2022
• Study Start: January 26, 2023
• Primary Completion (Estimated): January 5, 2027
• Study Completion (Estimated): July 6, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)