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

NCT04665765 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: 20148NCI-2020-08524P30CA033572
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief 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). 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.

Conditions

Diffuse Large B-Cell Lymphoma Unclassifiable; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Recurrent Transformed B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Transformed B-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

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

• 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.

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

Secondary Outcomes (1)

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

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

Study Arms (1)

Treatment (PolaR-ICE)

EXPERIMENTAL

SALVAGE 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.

Drug: Carboplatin; Drug: Etoposide; Drug: Ifosfamide; Drug: Polatuzumab Vedotin; Biological: Rituximab

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (PolaR-ICE)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16

Treatment (PolaR-ICE)

Ifosfamide DRUG

Given IV

Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942

Treatment (PolaR-ICE)

Polatuzumab Vedotin DRUG

Given IV

Also known as: ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711, polatuzumab vedotin-piiq, Polivy, RG7596, Ro 5541077-000

Treatment (PolaR-ICE)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Treatment (PolaR-ICE)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Carboplatin; Etoposide; Ifosfamide; polatuzumab vedotin; Rituximab; CT-P10

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)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Alex Herrera , MD
• Organization: City of Hope Medical Center

aherrera@coh.org

6263598111

Study Officials

• Alex F Herrera

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 14, 2020
• Study Start: January 18, 2021
• Primary Completion: July 26, 2022
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 3, 2025
• Results First Posted: August 26, 2024

Record last verified: 2025-08

Locations

US (2)