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A Study to Evaluate the Safety and Efficacy of Polatuzumab Vedotin in Combination With Rituximab, Gemcitabine and Oxaliplatin Compared to Rituximab, Gemcitabine and Oxaliplatin Alone in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (POLARGO)

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ClinicalTrials.gov Identifier: NCT04182204
Recruitment Status : Recruiting
First Posted : December 2, 2019
Last Update Posted : July 14, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with rituximab, gemcitabine and oxaliplatin (R-GemOx) in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study comprises of two stages: a safety run-in stage and a randomized controlled trial.

Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Drug: Polatuzumab Vedotin Drug: Rituximab Drug: Gemcitabine Drug: Oxaliplatin Phase 3

Detailed Description:
The safety run-in stage (Stage 1) will assess the safety of polatuzumab vedotin plus rituximab, gemcitabine and oxaliplatin (Pola-R-GemOx) in 10 participants. The randomized controlled trial (RCT) (Stage 2) will compare Pola-R-GemOx versus R-GemOx in 206 participants.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 216 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: In stage 1 participants are all assigned to one group. In stage 2 participants are assigned to two groups in parallel for the duration of the study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Open-Label, Multicenter, Randomized, Study Evaluating the Safety and Efficacy of Polatuzumab Vedotin in Combination With Rituximab Plus Gemcitabine Plus Oxaliplatin (R-GEMOX) Versus R-GEMOX in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Actual Study Start Date : February 7, 2020
Estimated Primary Completion Date : July 18, 2023
Estimated Study Completion Date : July 18, 2023


Arm Intervention/treatment
Experimental: Pola-R-GemOx (Stage 1)
Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) for a maximum dose of 240 mg per cycle (mg/cycle) administered intravenously (IV) and rituximab 375 milligrams per square meter (mg/m^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
Drug: Polatuzumab Vedotin
polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle IV on Day 1 of each 21-day cycle for up to 8 cycles.

Drug: Rituximab
rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle for up to 8 cycles.
Other Name: Mabthera; Rituxan

Drug: Gemcitabine
gemcitabine 1000 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycles.

Drug: Oxaliplatin
oxaliplatin 100 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycle.

Experimental: Pola-R-GemOx (Stage 2)
Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) for a maximum dose of 240 mg/cycle administered intravenously (IV) and rituximab 375 milligrams per square meter (mg/m^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
Drug: Polatuzumab Vedotin
polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle IV on Day 1 of each 21-day cycle for up to 8 cycles.

Drug: Rituximab
rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle for up to 8 cycles.
Other Name: Mabthera; Rituxan

Drug: Gemcitabine
gemcitabine 1000 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycles.

Drug: Oxaliplatin
oxaliplatin 100 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycle.

Active Comparator: R-GemOx (Stage 2)
Participants will receive rituximab 375 milligrams per square meter (mg/m^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
Drug: Rituximab
rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle for up to 8 cycles.
Other Name: Mabthera; Rituxan

Drug: Gemcitabine
gemcitabine 1000 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycles.

Drug: Oxaliplatin
oxaliplatin 100 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycle.




Primary Outcome Measures :
  1. Stage 1: Percentage of Participants with Adverse Events (AEs) [ Time Frame: From baseline until 90 days after last dose ]
  2. Stage 2: Overall Survival (OS) [ Time Frame: From randomization until end of study (up to approximately 25 months) ]
    Overall survival was defined as the time from the date of randomization to the date of death from any cause.


Secondary Outcome Measures :
  1. Stage 1: Percentage of Participants with Peripheral Neuropathy [ Time Frame: From baseline up to approximately 44 months ]
    Peripheral neuropathy will be measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item Scale (FACT-GOG/Ntx12). FACT-GOG/Ntx12 is a 12-item self-reported questionnaire designed to measure chemotherapy-induced peripheral neuropathy and contains 12 items, covering sensory neuropathy, motor neuropathy, hearing neuropathy, and dysfunction associated with neuropathy.

  2. Stage 1: Percentage of Participants with Polatuzumab Vedotin Dose Interruptions and Dose Reductions [ Time Frame: From baseline until 28 days after last dose ]
  3. Stage 1: Polatuzumab Vedotin Dose Intensity [ Time Frame: From baseline until 28 days after last dose ]
    Dose intensity is defined as the ratio of actual dose administered versus intended dose.

  4. Stage 1: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin at Baseline [ Time Frame: Baseline ]
  5. Stage 1: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin Post-Baseline [ Time Frame: Baseline up until Month 2 of the Post-Treatment Follow-up period ]
  6. Stage 1: Percentage of Participants with Complete Response (CR) [ Time Frame: From baseline up to approximately 44 months ]
    CR was defined as complete metabolic response assessed by the investigator through PET-CT Scan according to Lugano 2014 response criteria.

  7. Stage 1: Percentage of Participants with Objective Response (OR) [ Time Frame: From baseline up to approximately 44 months ]
    OR is defined as complete metabolic response (CR) or partial metabolic response (PR) and will be assessed by the investigator through PET-CT scan according to Lugano 2014 response criteria.

  8. Stage 1: Best Overall Response (BOR) [ Time Frame: From baseline up to approximately 44 months ]
    BOR is defined as the best response recorded from the start of treatment until end of treatment (based on PET-CT or CT data) according to Lugano 2014 response criteria, determined by the investigator

  9. Stage 1: Progression Free Survival (PFS) [ Time Frame: From baseline up to approximately 44 months ]
    PFS is defined as the time from enrollment to the first occurrence of disease progression (as determined by the investigator according to Lugano 2014 response criteria) or death.

  10. Stage 1: Overall Survival (OS) [ Time Frame: From baseline up to approximately 44 months ]
    OS is defined as the time from enrollment to death from any cause.

  11. Stage 1: Event Free Survival (EFS) [ Time Frame: From baseline up to approximately 44 months ]
    EFS is defined as the time from enrollment to the first occurrence of disease progression or relapse, death due to any cause or initiation of any non-protocol-specified antilymphoma treatment (NALT).

  12. Stage 1: Observed Serum Concentration of Polatuzumab Vedotin Total Antibody (µg/mL) [ Time Frame: Pre- and post-dose (infusion duration=90 minutes [min]) on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1 (Cycle length=21 days), at treatment completion/early termination and randomly during post-treatment follow up (2 months) ]
  13. Stage 1: Observed Plasma Concentrations of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (acMMAE) and Unconjugated MMAE (ng/mL) [ Time Frame: Pre- and post-dose (infusion duration=90 minutes [min]) on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1 (Cycle length=21 days), at treatment completion/early termination and randomly during post-treatment follow up (2 months) ]
  14. Stage 2: Percentage of Participants with Objective Response (OR) [ Time Frame: From randomization until up to 25 months ]

    OR is defined as CR or PR and will be assessed by an Independent review committee through PET-CT scan according to Lugano 2014 response criteria.

    OR will also be assessed by the investigator using Response alone (not including PET data) and will consider complete response instead of complete metabolic response.


  15. Stage 2: Percentage of Participants with Complete Response (CR) [ Time Frame: From randomization until up to 25 months ]

    CR will be assessed by an Independent review committee through PET-CT scan according to Lugano 2014 response criteria.

    CR will also be assessed by the Investigator using Response (not including PET data) and will consider complete response instead of complete metabolic response.


  16. Stage 2: Best Overall Response (BOR) [ Time Frame: From randomization until up to 25 months ]
    BOR is defined as the best response recorded from the start of treatment until end of treatment (based on PET-CT or CT data) according to Lugano 2014 response criteria, determined by the investigator

  17. Stage 2: Progression Free Survival (PFS) [ Time Frame: From randomization until up to 25 months ]
    PFS is defined as the time from the time of randomization to the first occurrence of disease progression (as determined by the investigator according to Lugano 2014 response criteria) or death.

  18. Stage 2: Duration of Response (DOR) [ Time Frame: From randomization until up to 25 months ]
    DOR will be assessed in patients who had an OR, as determined by the investigator, using Lugano 2014 response criteria. DOR is defined as the time interval from the date of the first occurrence of a CR or PR (whichever status is recorded first) until the first date that progressive disease or death is documented, whichever occurs first.

  19. Stage 2: Event Free Survival (EFS) [ Time Frame: From randomization until up to 25 months ]
    EFS is defined as the time from enrollment to the first occurrence of disease progression or relapse, death due to any cause or initiation of NALT.

  20. Stage 2: Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score [ Time Frame: Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 25 months) ]
    The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS.

  21. Stage 2: Time to Deterioration in Physical Functioning and Fatigue [ Time Frame: Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 25 months) ]
    Time to deterioration in physical functioning and fatigue is defined as the time from randomization to the first documentation of a 10-point decrease in EORTC QLQ-C30 physical functioning and fatigue scales from baseline. The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS.

  22. Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score [ Time Frame: Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 25 months) ]
    The FACT-Lym is a validated health-related quality of life (HRQoL) instrument used specifically in patients with lymphoma. It is composed of the 27-item FACT-general questionnaire (FACT-G), which measures health-related quality of life in patients undergoing any type of cancer therapy, plus the 15-item Lymphoma-Specific Subscale (FACT-Lym LYMS), which assesses the HRQoL impacts of more lymphoma-specific symptoms. Each item of the FACT-Lym is answered using a 5-point scale ranging from 0 = "not at all" to 4 = "very much". 0 = Not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, and 4 = Very much. FACT-LYM total score can be calculated and higher scores are reflective of better HRQoL.

  23. Stage 2: Time to Progression in Lymphoma Symptoms According to FACT-Lym Subscale [ Time Frame: Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 25 months) ]
    Time to progression is defined as the time from randomization to the first documentation of a 3-point decrease (clinically meaningful change) from baseline.

  24. Stage 2: Change from Baseline in Peripheral Neuropathy According to FACT/GOG-NTX-12 Subscale Score [ Time Frame: Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 25 months) ]
    FACT/GOG-Ntx12 is a 12-item self-reported questionnaire designed to measure chemotherapy-induced peripheral neuropathy and contains 12 items, covering sensory neuropathy, motor neuropathy, hearing neuropathy, and dysfunction associated with neuropathy. It is answered using a 5-point scale ranging from 0 = "not at all" to 4 = "very much". 0 = Not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, and 4 = Very much. FACT/GOG-Ntx12 subscale scores can be calculated with higher scores reflective of a better outcome.

  25. Stage 2: Percentage of Participants with Adverse Events (AEs) [ Time Frame: From randomization until up to 25 months ]
  26. Stage 2: Percentage of Participants with Polatuzumab Vedotin Dose Interruptions and Dose Reductions [ Time Frame: From randomization until up to 25 months ]
  27. Stage 2: Polatuzumab Vedotin Dose Intensity [ Time Frame: From randomization until up to 25 months ]
    Dose intensity is defined as the ratio of actual dose administered versus intended dose.

  28. Stage 2: Percentage of Participants with Peripheral Neuropathy [ Time Frame: From randomization until up to 25 months ]
    Peripheral neuropathy will be measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item Scale (FACT-GOG/Ntx12). FACT-GOG/Ntx12 is a 12-item self-reported questionnaire designed to measure chemotherapy-induced peripheral neuropathy and contains 12 items, covering sensory neuropathy, motor neuropathy, hearing neuropathy, and dysfunction associated with neuropathy.

  29. Stage 2: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin at Baseline [ Time Frame: Baseline ]
  30. Stage 2: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin Post-Baseline [ Time Frame: Baseline up until Month 2 of the Post-Treatment Follow-up period ]
  31. Stage 2: Observed Serum Concentration of Polatuzumab Vedotin Total Antibody (µg/mL) [ Time Frame: Pre- and post-dose (infusion duration=90 minutes [min]) on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1 (Cycle length=21 days), at treatment completion/early termination and randomly during post-treatment follow up (2 months) ]
  32. Stage 2: Observed Plasma Concentrations of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (acMMAE) and Unconjugated MMAE (ng/mL) [ Time Frame: Pre- and post-dose (infusion duration=90 minutes [min]) on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1 (Cycle length=21 days), at treatment completion/early termination and randomly during post-treatment follow up (2 months) ]


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:

  • Histologically-confirmed diffuse large B-cell lymphoma, not otherwise specified (NOS) or history of transformation of indolent disease to DLBCL
  • Relapsed disease (disease that has recurred following a response that lasted ≥ 6 months from completion of the last line of therapy) or refractory disease (disease that progressed during therapy or progressed within 6 months (< 6 months) of prior therapy)
  • At least one (≥ 1) line of prior systemic therapy:
  • Patients may have undergone autologous hematopoietic stem cell transplantation (HSCT) prior to recruitment; chemotherapy followed by consolidative autologous HSCT will be counted as one line of therapy
  • Patients may have undergone allogeneic HSCT prior to recruitment, so long as they are off all immunosuppressive therapy and have no active GVHD; chemotherapy followed by allogeneic HSCT will be counted as one line of therapy
  • Local therapies (e.g., radiotherapy) will not be considered as lines of treatment
  • At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or MRI
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
  • Adequate hematological function
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm,

Exclusion Criteria:

  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
  • Contraindication to rituximab, gemcitabine or oxaliplatin
  • Peripheral neuropathy assessed to be > Grade 1 according to NCI CTCAE v5.0
  • Prior use of polatuzumab vedotin or a gemcitabine plus platinum-based agent combination, recent participation in a clinical trial, and/or treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy within 2 weeks
  • Planned autologous or allogenic stem cell transplantation at time of recruitment
  • Primary or secondary central nervous system (CNS) lymphoma
  • Richter's transformation or prior CLL
  • Abnormal laboratory values or health conditions, as assessed by the investigator, any known conditions preventing adherence to protocol or active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
  • Vaccination with a live vaccine within 4 weeks prior to treatment
  • Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1) other than for diagnosis
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the last dose of study drug
  • Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug

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): NCT04182204


Contacts
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Contact: MO40598 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04182204    
Other Study ID Numbers: MO40598
2018-003727-10 ( EudraCT Number )
First Posted: December 2, 2019    Key Record Dates
Last Update Posted: July 14, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoffmann-La Roche:
Lymphoma
Large B-Cell
Diffuse
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Gemcitabine
Rituximab
Oxaliplatin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents