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

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ClinicalTrials.gov Identifier: NCT04665765
Recruitment Status : Recruiting
First Posted : December 14, 2020
Last Update Posted : October 5, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

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.

Condition or disease Intervention/treatment Phase
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 Drug: Carboplatin Drug: Etoposide Drug: Ifosfamide Drug: Polatuzumab Vedotin Biological: Rituximab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 18, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023


Arm Intervention/treatment
Experimental: Treatment (PolaR-ICE)

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
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16

Drug: Ifosfamide
Given IV
Other Names:
  • 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

Drug: Polatuzumab Vedotin
Given IV
Other Names:
  • ADC DCDS4501A
  • Antibody-Drug Conjugate DCDS4501A
  • DCDS4501A
  • FCU 2711
  • polatuzumab vedotin-piiq
  • Polivy
  • RG7596
  • Ro 5541077-000

Biological: Rituximab
Given IV
Other Names:
  • 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




Primary Outcome Measures :
  1. Complete response (CR) rate of polatuzumab vedotin (Pola) added to rituximab, ifosfamide, carboplatin, and etoposide (PolaR-ICE) salvage therapy [ Time Frame: After 2 cycles of salvage therapy (each cycle is 21 days) ]
    Estimated by the proportion of response-evaluable patients achieving CR after 2 cycles of salvage therapy, along with the 95% exact binomial confidence interval.

  2. Incidence of toxicity of PolaR-ICE salvage therapy [ Time Frame: During the first 2 cycles of treatment (each cycle is 21 days) ]
    Defined as any of the following events occurring during the first 2 cycles of treatment that is at least possibly related to study treatment. Observed toxicities of PolaR-ICE salvage therapy will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity, and attribution.


Secondary Outcome Measures :
  1. Incidence of toxicity of single-agent polatuzumab vedotin (Pola) consolidation therapy [ Time Frame: Up to 30 days post-last dose ]
    Observed toxicities of PolaR-ICE Pola single-agent consolidation therapy will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity, and attribution.

  2. Overall response rate (ORR) to PolaR-ICE [ Time Frame: Up to 2 years ]
    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.

  3. Progression-free survival (PFS) [ Time Frame: Time from start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 2 years ]
    Estimated using the product limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation. Median PFS will be estimated when available.

  4. Overall survival (OS) [ Time Frame: Time from start of protocol treatment to time of death due to any cause, assessed up to 2 years ]
    Estimated using the product limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation. Median OS will be estimated when available.

  5. CR rate among patients who were PR at autologous stem cell transplant (ASCT) [ Time Frame: Up to 2 years ]
    Defined as the proportion of patients that achieve CR after Pola consolidation among those who were PR at ASCT.

  6. Stem cell mobilization failure rate [ Time Frame: Up to 2 years ]
    Defined as the portion of patients who failed to collect adequate CD34 stem cells (within 2 attempts) among those who attempt stem cell collection.


Other Outcome Measures:
  1. Circulating tumor deoxyribonucleic acid (ctDNA) analysis [ Time Frame: Up to 2 years ]
    Descriptive statistics will be used to summarize ctDNA analysis.

  2. Biomarker analysis [ Time Frame: Up to 2 years ]
    Descriptive statistics will be used to summarize biomarker analysis.



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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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)

Exclusion Criteria:

  • 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)
  • 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)

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): NCT04665765


Locations
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United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Alex F. Herrera    626-256-4673 ext 82405    aherrera@coh.org   
Principal Investigator: Alex F. Herrera         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jonathon Cohen, MD    404-778-0519    jonathon.cohen@emory.edu   
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Alex F Herrera City of Hope Medical Center
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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT04665765    
Other Study ID Numbers: 20148
NCI-2020-08524 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
20148 ( Other Identifier: City of Hope Medical Center )
P30CA033572 ( U.S. NIH Grant/Contract )
First Posted: December 14, 2020    Key Record Dates
Last Update Posted: October 5, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Recurrence
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes
Rituximab
Antineoplastic Agents, Immunological
Carboplatin
Etoposide
Etoposide phosphate
Ifosfamide
Isophosphamide mustard
Podophyllotoxin
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antirheumatic Agents
Antineoplastic Agents, Phytogenic