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Diffuse Large B-Cell LymphomaPhase 1/2NCT05455697

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

A Phase 1/2 study testing Bone Marrow Biopsy, Cyclophosphamide and Doxorubicin in people with Diffuse Large B-Cell Lymphoma and Grade 3b Follicular Lymphoma, run by University of Washington at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bone Marrow Biopsy, Cyclophosphamide and Doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
1 siteUnited States
Study dates
26 Jan 2023to 5 Jan 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Left ventricular ejection fraction of >= 45%, assessed by echocardiography or cardiac multi-gated acquisition (MUGA) scan
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual activity starting with the first dose of study therapy and for 180 days after the last dose of study medication. Female subjects of childbearing potential must also agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial and for 180 days after receiving the last dose of study therapy. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use 2 methods of contraception starting with the first dose of study therapy and for 180 days after the last dose of study therapy

Who cannot join

  • 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
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  • 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
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 180 days after the last dose of trial treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies), unless controlled on therapy and CD4 count is > 200/uL
  • Has known active Hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive or hepatitis B virus [HBV] deoxyribonucleic acid [DNA] detectable) or Hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Immunostart: Prephase Tafasitamab, Retifanlimab, and Rituximab (TRR), Followed by TRR With Standard Therapy for Previously Untreated Diffuse Large B-Cell Lymphoma

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.

Read the detailed description

OUTLINE:

PREPHASE THERAPY: Patients receive tafasitamab intravenously (IV) over 30 minutes on days 1, 8, and 15 of each cycle, rituximab and hyaluronidase human subcutaneously (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 international prognostic index (IPI) score of 2-5 may receive polatuzumab vedotin IV in place of vincristine at investigator discretion. Patients also receive prednisone orally (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.

Patients also undergo optional bone marrow biopsy and aspiration and multi-gated acquisition (MUGA) scan at screening, and fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan and collection of blood and tissue samples throughout the trial.

After completion of study treatment, patients are followed up at 4-6 weeks, 12 weeks and then per routine care for up to 5 years.

Being tested
Bone Marrow Biopsy, Cyclophosphamide, Doxorubicin, Prednisone, Retifanlimab
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bone Marrow BiopsyProcedure or surgery

    Undergo bone marrow biopsy

  • CyclophosphamideDrug

    Also called Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal

    Given IV

  • DoxorubicinDrug

    Also called 14-Hydroxydaunomycin, 23214-92-8, Adriablastin, Hydroxydaunomycin

    Given IV

  • PrednisoneDrug

    Also called Dehydrocortisone, Adasone, Cortancyl, Dacortin

    Given PO

  • RetifanlimabBiological

    Also called 2226345-85-1, INCMGA 0012, INCMGA-0012, INCMGA00012

    Given IV

  • Rituximab and Hyaluronidase HumanBiological

    Also called Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human

    Given SC

  • TafasitamabBiological

    Also called 1422527-84-1, Immunoglobulin, Anti-(Human Cd19 Antigen) (Human-mus musculus Monoclonal MOR00208 Heavy Chain), Disulfide with Human-mus musculus Monoclonal MOR00208 .Kappa.-chain,

    Given IV

  • VincristineDrug

    Also called 22-Oxovincaleukoblastine, 57-22-7, LEUROCRISTINE, VCR, Vincrystine

    Given vincristine

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Fludeoxyglucose F-18Other

    Also called 105851-17-0, 18FDG

    Undergo FDG-PET/CT

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, PET Scan, Positron Emission Tomography Scan

    Undergo FDG-PET

  • Computed TomographyProcedure or surgery

    Also called CAT Scan, Computed Axial Tomography, CT SCAN

    Undergo FDG-CT

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection

    Undergo collection of blood samples

  • Polatuzumab VedotinDrug

    Also called Antibody-Drug Conjugate DCDS4501A, Polivy

    Given IV

Study groups in NCT05455697
Study groupRoleWhat they receive
Treatment (TRR, CHOP)ExperimentalPREPHASE 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (5)

  1. Overall response rate

    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.

    Measured: Up to 5 years

  2. Progression-free survival

    Time-to-event analyses for progression-free survival will be conducted using the Kaplan-Meier method and log-rank test. 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.

    Measured: 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

  3. Overall survival

    Time-to-event analyses for overall survival will be conducted using the Kaplan-Meier method and log-rank test. 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.

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

  4. Proportion completing prephase

    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.

    Measured: Up to 5 years

  5. Relative dose intensity of doxorubicin and cylcophosphamide during combination therapy

    Relative dose intensity for doxorubicin and cyclophosphamide will be calculated as follows:

    • Standard dose intensity (SDI): (Standard total dose, in mg/m2 )/(standard time to complete chemotherapy, in days
    • Delivered dose intensity (DDI): (Delivered total dose, in mg/m2)/(actual time to complete chemotherapy, in days)
    • Relative dose intensity: DDI/SDI x 100% 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.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2022
  2. Study start26 Jan 2023
  3. Primary completion15 Oct 2026
  4. Study completion5 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05455697
Sponsor's protocol ID
RG1122398
Other IDs
NCI-2022-04527, RG1122398, 10946
Status last verified
Oct 2026
First submitted
17 Jun 2022
Last updated
30 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bone Marrow Biopsy, Cyclophosphamide and Doxorubicin in people with Diffuse Large B-Cell Lymphoma and Grade 3b Follicular Lymphoma, run by University of Washington at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity rate (time frame: From treatment start to end of cycle 3 (each cycle is 3 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05455697.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.

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