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Diffuse Large B-Cell Lymphoma UnclassifiablePhase 2NCT04665765

Polatuzumab Vedotin, Rituximab, Ifosfamide, Carboplatin, and Etoposide (PolaR-ICE) as Initial Salvage Therapy for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

A Phase 2 study testing Carboplatin, Etoposide and Ifosfamide in people with Diffuse Large B-Cell Lymphoma Unclassifiable and Recurrent Diffuse Large B-Cell Lymphoma, run by City of Hope Medical Center at 2 sites 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 II trial studies the effect of polatuzumab vedotin, rituximab, ifosfamide, carboplatin, and etoposide as initial salvage therapy in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carboplatin, Etoposide and Ifosfamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
2 sitesUnited States
Study dates
18 Jan 2021to 28 Jun 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Documented informed consent of the participant and/or legally authorized representative
  • Assent, when appropriate, will be obtained per institutional guidelines
  • Be willing to provide archival tissue of a biopsy that was performed after the frontline systemic therapy
  • If unavailable, exceptions may be granted with study principal investigator (PI) approval
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • Histologically confirmed diagnosis of diffuse large B-cell lymphoma according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution. Subtypes of DLBCL including transformed indolent lymphomas (TIL), primary mediastinal large B-cell lymphoma (PMBCL), and aggressive B-cell lymphoma unclassified (BCL-U) are eligible
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  • Biopsy-proven relapsed or refractory disease after 1 line of frontline CD20-directed immunotherapy with anthracycline- or anthracenedione-based multi-agent chemotherapy. Monotherapy with rituximab or other CD20-directed immunotherapy prior to frontline chemotherapy or as maintenance therapy, and radiation therapy in a limited field or as a part of the frontline treatment plan are permitted
  • Prior lymphoma therapy should be completed at least 2 weeks before start of protocol therapy
  • Measurable disease by computed tomography (CT) or positron emission tomography (PET)/CT scan with one or more sites of disease >= 1.5 cm in longest dimension
  • Considered eligible for high-dose chemotherapy followed by ASCT
  • Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 to prior anti-cancer therapy
  • Absolute neutrophil count (ANC) >= 1,000/mm^3 (without bone marrow involvement)
  • NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
  • ANC >= 750/mm^3 (with bone marrow involvement)
  • NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
  • Platelets >= 100,000/mm^3 (without bone marrow involvement)
  • NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
  • Platelets >= 75,000/mm^3 (with bone marrow involvement)
  • NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
  • Hemoglobin >= 8 g/dL (no erythropoietin and/or packed red blood cells (pRBC) transfusion allowed within 7 days prior to screening)
  • Total bilirubin =< 1.5 X upper limit of normal (ULN). If hepatic involvement by lymphoma, or Gilbert's disease: =< 3 X ULN
  • Aspartate aminotransferase (AST) =< 2.5 x ULN. If hepatic involvement by lymphoma: AST =< 5 x ULN
  • Alanine aminotransferase (ALT) =< 2.5 x ULN. If hepatic involvement by lymphoma: ALT =< 5 x ULN
  • Creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula
  • If not receiving anticoagulants: international normalized ratio (INR) OR prothrombin (prothrombin time [PT]) =< 1.5 x ULN. If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
  • If not receiving anticoagulants: activated partial thromboplastin time (aPTT) =< 1.5 x ULN. If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 12 months after the last dose of polatuzumab vedotin or rituximab for women, at least 5 months following the last dose of polatuzumab vedotin or 3 months following the last dose of rituximab for men, and at least 6 months following the last dose of ifosfamide, carboplatin, or etoposide for both women and men
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Who cannot join

  • Patients who are not hematopoietic stem cell transplant candidates are excluded
  • Prior solid organ transplantation
  • Systemic steroid therapy or any other form of immunosuppressive therapy for lymphoma symptom control must be tapered down to =< 10 mg/day prednisone or equivalent. Exceptions are:
  • Inhaled or topical steroids
  • Adrenal replacement doses > 10 mg daily prednisone equivalents in the absence of active autoimmune disease
  • Peripheral neuropathy >= grade 2 or demyelinating form of Charcot-Marie-Tooth disease
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  • Known active central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement
  • Active infection requiring systemic therapy
  • Other active malignancy requiring therapy. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
  • Recent major surgery (within 4 weeks) prior to start of protocol therapy, other than for diagnosis
  • Symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, and symptomatic arrhythmias), cerebrovascular event/stroke or myocardial infarction within the past 6 months
  • Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with past HBV infection (defined as negative hepatitis B surface antigen [HBsAg] and positive hepatitis B core antibody [HBcAb]) are eligible if HBV DNA is undetectable. Patients who are positive for HCV antibody are eligible if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). Testing to be done only in patients suspected of having infections or exposures
  • Known active human immunodeficiency virus (HIV) infection. Subjects who have an undetectable or unquantifiable HIV viral load with CD4 >= 200 and are on highly active antiretroviral therapy (HAART) medication are allowed. Testing to be done only in patients suspected of having infections or exposures
  • History of or current progressive multifocal leukoencephalopathy (PML)
  • Females only: Pregnant or breastfeeding
  • Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Emory University

    Atlanta, Georgia, 30322

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase 2 Study of Polatuzumab Vedotin With Rituximab, Ifosfamide, Carboplatin, and Etoposide (PolaR-ICE) as Initial Salvage Therapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma

This phase II trial studies the effect of polatuzumab vedotin, rituximab, ifosfamide, carboplatin, and etoposide as initial salvage therapy in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Polatuzumab vedotin is a monoclonal antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79b positive cancer cells in a targeted way and delivers vedotin to kill them. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as ifosfamide, carboplatin, and etoposide, 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 chemotherapy with immunotherapy may kill more cancer cells in patients with diffuse large B-cell lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the safety and tolerability of polatuzumab vedotin (Pola) added to rituximab, ifosfamide, carboplatin, and etoposide (PolaR-ICE) as first salvage therapy for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). (Safety Lead-in) II. Evaluate the anti-tumor activity of PolaR-ICE as first salvage therapy for R/R DLBCL as assessed by the complete response rate after 2 cycles. (Phase 2)

SECONDARY OBJECTIVES:

  1. Evaluate the overall response rate to PolaR-ICE as first salvage therapy for R/R DLBCL.

II. Evaluate the progression-free and overall survival of patients who received PolaR-ICE as first salvage therapy for R/R DLBCL followed by autologous stem cell transplantation (ASCT) and single-agent Pola consolidation after ASCT.

III. Evaluate the CR rate after Pola consolidation among those who were partial response (PR) at ASCT.

IV. Evaluate the toxicity of PolaR-ICE salvage therapy and that of Pola consolidation after ASCT.

  1. Assess the rate of stem cell mobilization and collection failure in patients with R/R DLBCL who receive PolaR-ICE as first salvage therapy.

EXPLORATORY OBJECTIVES:

  1. Assess the kinetics of circulating tumor deoxyribonucleic acid (DNA) after PolaR-ICE as first salvage therapy for R/R DLBCL followed by ASCT and single-agent Pola consolidation after ASCT.

II. Assess possible biomarkers of response to PolaR-ICE in patients with R/R DLBCL.

III. Examine the association between clinical outcomes (response, progression-free survival [PFS]) and pathological tumor characteristics.

IV. Examine the association between clinical outcomes (response, PFS) and circulating tumor (ct)DNA characteristics (mutation profile, kinetics of clearance).

OUTLINE:

SALVAGE THERAPY: Patients receive polatuzumab vedotin intravenously (IV) on day 1, rituximab IV on day 1, etoposide IV on days 1-3, carboplatin IV on day 2, and ifosfamide IV on day 2 or days 1-3. Treatment repeats every 21 days for up to 2-3 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response, partial response or stable disease by cycle 2 day 15 (C2D15) may receive 1 additional cycle of PolaR-ICE IV.

CONSOLIDATION THERAPY: Within 30-60 days after ASCT, patients receive polatuzumab vedotin IV on day 1. Treatment repeats every 21 days for up to 3-4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then periodically for up to 2 years.

Being tested
Carboplatin, Etoposide, Ifosfamide, Polatuzumab Vedotin, Rituximab
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.

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • IfosfamideDrug

    Also called Asta Z 4942, Asta Z-4942, Cyfos, Holoxan

    Given IV

  • Polatuzumab VedotinDrug

    Also called ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711

    Given IV

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

Study groups in NCT04665765
Study groupRoleWhat they receive
Treatment (PolaR-ICE)ExperimentalSALVAGE THERAPY: Patients receive polatuzumab vedotin IV on day 1, rituximab IV on day 1, etoposide IV on days 1-3, carboplatin IV on day 2, and ifosfamide IV on day 2 or days 1-3. Treatment repeats every 21 days for up to 2-3 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response, partial response or stable disease by C2D15 may receive 1 additional cycle of PolaR-ICE IV. CONSOLIDATION THERAPY: Within 30-60 days after ASCT, patients receive polatuzumab vedotin IV on day 1. Treatment repeats every 21 days for up to 3-4 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carboplatin; Drug: Etoposide; Drug: Ifosfamide; Drug: Polatuzumab Vedotin; Biological: Rituximab

What is being measured

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

  1. Complete Response (CR) Rate After Two Cycles of PolaR-ICE Salvage Therapy

    Estimated by the proportion of response-evaluable patients achieving CR after 2 cycles of salvage therapy, along with the 95% exact binomial confidence interval. Polatuzumab vedotin (Pola) was added to rituximab, ifosfamide, carboplatin, and etoposide (PolaR-ICE) as salvage therapy.

    Measured: After 2 cycles of salvage therapy (each cycle is 21 days)

  2. Number of Unacceptable Toxicities of PolaR-ICE Salvage Therapy (Phase 2 Stage)

    Unacceptable toxicity was defined as the events in Section 11.2 occurring during the first 2 cycles of treatment that was at least possibly related to study treatment.

    Measured: During the first 2 cycles of PolaR-ICE salvage therapy (each cycle is 21 days)

  3. Number of Unacceptable Toxicities of PolaR-ICE Salvage Therapy (Safety lead-in Stage)

    Unacceptable toxicity was defined as the events in Section 11.2 occurring during the first 2 cycles of treatment that was at least possibly related to study treatment.

    Measured: During the first 2 cycles of PolaR-ICE salvage therapy (each cycle is 21 days)

Secondary outcomes (1)

  1. Overall Response Rate (ORR) of the PolaR-ICE Salvage Therapy

    Estimated by the proportion of response-evaluable participants that achieve a best response of either CR or partial response (PR) at the end of PolaR-ICE therapy, along with the 95% exact binomial confidence interval. Polatuzumab vedotin (Pola) was added to rituximab, ifosfamide, carboplatin, and etoposide (PolaR-ICE) as salvage therapy.

    Measured: From initial treatment to the end of salvage therapy (up to three cycles).

Timeline

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

  1. First posted14 Dec 2020
  2. Study start18 Jan 2021
  3. Primary completion26 Jul 2022
  4. Study completion28 Jun 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04665765
Sponsor's protocol ID
20148
Other IDs
NCI-2020-08524, 20148, P30CA033572
Status last verified
Aug 2026
First submitted
7 Dec 2020
Last updated
11 Sep 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Shouse G, Matasar M, Chen L, Crombie J, Cohen J, Advani R, LaCasce A, Popplewell L, Puverel S, Peters L, Daniels S, Godfrey J, Mei M, Thiruvengadam S, Budde LE, Nikolaenko L, Rosen ST, Kwak LW, Forman SJ, Herrera AF. Polatuzumab Vedotin Combined With R-ICE (PolaR-ICE) as Second-Line Therapy in Diffuse Large B-Cell Lymphoma. Am J Hematol. 2026 Jun;101(6):1273-1282. doi: 10.1002/ajh.70282. Epub 2026 Mar 17.

    PubMed 41845899

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carboplatin, Etoposide and Ifosfamide in people with Diffuse Large B-Cell Lymphoma Unclassifiable and Recurrent Diffuse Large B-Cell Lymphoma, run by City of Hope Medical Center at 2 sites 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 29 inclusion and 18 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 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 phase mean?

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?

Yes. Results are posted in the registry (first posted 26 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Complete Response (CR) Rate After Two Cycles of PolaR-ICE Salvage Therapy (time frame: After 2 cycles of salvage therapy (each cycle is 21 days)). The study lists 3 primary outcomes in all. 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 NCT04665765, which also lists 1 linked publication.

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 11 Sep 2026.

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