Clinical Trials /

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

NCT04182204

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Transformed Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: MO40598
  • SECONDARY ID: 2018-003727-10
  • NCT ID: NCT04182204

Conditions

  • Diffuse Large B-Cell Lymphoma

Interventions

DrugSynonymsArms
Polatuzumab VedotinPola-R-GemOx (Stage 1)
RituximabMabthera; RituxanPola-R-GemOx (Stage 1)
GemcitabinePola-R-GemOx (Stage 1)
OxaliplatinPola-R-GemOx (Stage 1)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Pola-R-GemOx (Stage 1)ExperimentalParticipants 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.
  • Polatuzumab Vedotin
  • Rituximab
  • Gemcitabine
  • Oxaliplatin
Pola-R-GemOx (Stage 2)ExperimentalParticipants 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.
  • Polatuzumab Vedotin
  • Rituximab
  • Gemcitabine
  • Oxaliplatin
R-GemOx (Stage 2)Active ComparatorParticipants 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.
  • Rituximab
  • Gemcitabine
  • Oxaliplatin

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Stage 1: Percentage of Participants with Adverse Events (AEs)
Time Frame:From baseline until 90 days after last dose
Safety Issue:
Description:Overall survival was defined as the time from the date of randomization to the date of death from any cause.

Secondary Outcome Measures

Measure:Stage 1: Percentage of Participants with Peripheral Neuropathy
Time Frame:From baseline up to approximately 44 months
Safety Issue:
Description: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.
Measure:Stage 1: Percentage of Participants with Polatuzumab Vedotin Dose Interruptions and Dose Reductions
Time Frame:From baseline until 28 days after last dose
Safety Issue:
Description:
Measure:Stage 1: Polatuzumab Vedotin Dose Intensity
Time Frame:From baseline until 28 days after last dose
Safety Issue:
Description:Dose intensity is defined as the ratio of actual dose administered versus intended dose.
Measure:Stage 1: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin
Time Frame:From baseline until 28 days after last dose
Safety Issue:
Description:
Measure:Stage 1: Percentage of Participants with Complete Response (CR)
Time Frame:From baseline up to approximately 44 months
Safety Issue:
Description:CR was defined as complete metabolic response assessed by the investigator through PET-CT Scan according to Lugano 2014 response criteria.
Measure:Stage 1: Percentage of Participants with Objective Response (OR)
Time Frame:From baseline up to approximately 44 months
Safety Issue:
Description: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.
Measure:Stage 1: Best Overall Response (BOR)
Time Frame:From baseline up to approximately 44 months
Safety Issue:
Description: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
Measure:Stage 1: Progression Free Survival (PFS)
Time Frame:From baseline up to approximately 44 months
Safety Issue:
Description: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.
Measure:Stage 1: Overall Survival (OS)
Time Frame:From baseline up to approximately 44 months
Safety Issue:
Description:OS is defined as the time from enrollment to death from any cause.
Measure:Stage 1: Event Free Survival (EFS)
Time Frame:From baseline up to approximately 44 months
Safety Issue:
Description: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).
Measure:Stage 1: Maximum Concentration (Cmax)
Time Frame:Pre and post-dose on Cycle 1 Day 1 (each cycle is 21 days), Cycle 2 Day 1, Cycle 4 Day 1, at treatment completion/early termination and randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:Cmax will be calculated for polatuzumab vedotin, gemcitabine and oxaliplatin.
Measure:Stage 1: Observed Trough Concentration (Ctrough)
Time Frame:Pre and post-dose on Cycle 1 Day 1 (each cycle is 21 days), Cycle 2 Day 1, Cycle 4 Day 1, at treatment completion/early termination and randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:Ctrough will be calculated for polatuzumab vedotin, gemcitabine and oxaliplatin.
Measure:Stage 2: Percentage of Participants with Objective Response (OR)
Time Frame:From randomization until up to 25 months
Safety Issue:
Description: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.
Measure:Stage 2: Percentage of Participants with Complete Response (CR)
Time Frame:From randomization until up to 25 months
Safety Issue:
Description: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.
Measure:Stage 2: Best Overall Response (BOR)
Time Frame:From randomization until up to 25 months
Safety Issue:
Description: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
Measure:Stage 2: Progression Free Survival (PFS)
Time Frame:From randomization until up to 25 months
Safety Issue:
Description: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.
Measure:Stage 2: Duration of Response (DOR)
Time Frame:From randomization until up to 25 months
Safety Issue:
Description: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.
Measure:Stage 2: Event Free Survival (EFS)
Time Frame:From randomization until up to 25 months
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:Time to progression is defined as the time from randomization to the first documentation of a 3-point decrease (clinically meaningful change) from baseline.
Measure: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)
Safety Issue:
Description: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.
Measure:Stage 2: Percentage of Participants with Adverse Events (AEs)
Time Frame:From randomization until up to 25 months
Safety Issue:
Description:
Measure:Stage 2: Percentage of Participants with Polatuzumab Vedotin Dose Interruptions and Dose Reductions
Time Frame:From randomization until up to 25 months
Safety Issue:
Description:
Measure:Stage 2: Polatuzumab Vedotin Dose Intensity
Time Frame:From randomization until up to 25 months
Safety Issue:
Description:Dose intensity is defined as the ratio of actual dose administered versus intended dose.
Measure:Stage 2: Percentage of Participants with Peripheral Neuropathy
Time Frame:From randomization until up to 25 months
Safety Issue:
Description: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.
Measure:Stage 2: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin
Time Frame:From randomization until up to 25 months
Safety Issue:
Description:
Measure:Stage 2: Maximum Concentration (Cmax)
Time Frame:Pre and post-dose on Cycle 1 Day 1 (each cycle is 21 days), Cycle 2 Day 1, Cycle 4 Day 1, at treatment completion/early termination and randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:Cmax will be calculated for polatuzumab vedotin, gemcitabine and oxaliplatin.
Measure:Stage 2: Observed Trough Concentration (Ctrough)
Time Frame:Pre and post-dose on Cycle 1 Day 1 (each cycle is 21 days), Cycle 2 Day 1, Cycle 4 Day 1, at treatment completion/early termination and randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:Ctrough will be calculated for polatuzumab vedotin, gemcitabine and oxaliplatin.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Trial Keywords

  • Lymphoma
  • Large B-Cell
  • Diffuse

Last Updated

January 31, 2020