A Study of Escalating Doses of Polatuzumab Vedotin in Participants With Relapsed or Refractory B-Cell Non-Hodgkins Lymphoma and Chronic Lymphocytic Leukemia and Polatuzumab Vedotin in Combination With Rituximab in Participants With Relapsed or Refractory B-Cell Non-Hodgkins Lymphoma
14 juni 2017 uppdaterad av: Genentech, Inc.
An Open-Label, Multicenter, Phase I Trial of the Safety and Pharmacokinetics Of Escalating Doses of DCDS4501A in Patients With Relapsed or Refractory B-Cell Non-Hodgkins Lymphoma and Chronic Lymphocytic Leukemia and DCDS4501A in Combination With Rituximab in Patients With Relapsed or Refractory B-Cell Non-Hodgkins Lymphoma
This is a Phase I, multicenter, open-label, dose-escalation study of polatuzumab vedotin administered as a single agent by intravenous (IV) infusion to participants with relapsed or refractory hematologic malignancies.
In Phase Ib, participants will receive polatuzumab vedotin in combination with rituximab.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Studietyp
Interventionell
Inskrivning (Faktisk)
95
Fas
- Fas 1
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Dijon, Frankrike, 21000
- CHU Dijon - SCE Hemato
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Lille, Frankrike
- Centre Hospitalier Regional Universitaire de Lille
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Montpellier, Frankrike, 34295
- CHU Lapeyronie, Hematologie
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Pierre Benite, Frankrike, 69495
- Centre Hospitalier Lyon Sud; Hematolgie
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Rouen, Frankrike, 76038
- Centre Henri Becquerel; Hematologie
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California
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Stanford, California, Förenta staterna, 94305-5820
- Stanford Cancer Center
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Stanford, California, Förenta staterna, 94305
- Stanford Cancer Institute Pharmacy
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Florida
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Sarasota, Florida, Förenta staterna, 34232
- Florida Cancer Specialists; Sarasota
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New York
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Buffalo, New York, Förenta staterna, 14263
- Roswell Park Cancer Inst.
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Tennessee
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Germantown, Tennessee, Förenta staterna, 38138
- Sarah Cannon Cancer Center
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Texas
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Houston, Texas, Förenta staterna, 77030
- M.D Anderson Cancer Center; Oncology
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Washington
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Seattle, Washington, Förenta staterna, 98109
- Fred Hutchinson Cancer Research Center
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Alberta
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Edmonton, Alberta, Kanada, T6G 1Z2
- Cross Cancer Institute ; Dept of Medical Oncology
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British Columbia
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Vancouver, British Columbia, Kanada, V5Z 1H6
- British Columbia Cancer Agency
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Quebec
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Montreal, Quebec, Kanada, H3T 1E2
- McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
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Amsterdam, Nederländerna, 1105 AZ
- Academisch Medisch Centrum; Hematologie
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria:
- Life expectancy of at least 12 weeks
- History of one of the following histologically-documented hematologic malignancy for which no effective standard therapy exists: indolent non Hodgkin's lymphoma (NHL), Grade 3b follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL)
- All participants (NHL and B-cell chronic lymphocytic leukemia [B-CLL]) must have at least one bi-dimensionally measurable lesion
- For all men or women of childbearing potential (unless surgically sterile): use of adequate methods of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly
Exclusion Criteria:
- Prior use of any monoclonal antibody or antibody-drug conjugate within 4 weeks before Cycle 1, Day 1
- Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent within 2 weeks prior to Cycle 1, Day 1. Adverse events from any previous treatments must be resolved or stabilized prior to Cycle 1, Day 1, except for neuropathy
- Completion of autologous stem cell transplant within 100 days prior to Cycle 1, Day 1
- Prior allogeneic stem cell transplant
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: Polatuzumab Vedotin
Polatuzumab vedotin will be administered by an IV infusion of escalating doses (starting dose of 0.1 mg/kg, potentially to be followed by 0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, and 4.0 mg/kg doses) every 3 weeks (q3w) (Day 1 of each 21 day cycle).
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Participants will receive escalating intravenous dose of polatuzumab vedotin.
Andra namn:
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Experimentell: Polatuzumab Vedotin + Rituximab
Polatuzumab vedotin will be administered by an IV infusion q3w (Day 1 of each 21 day cycle).
Rituximab was administered by an IV infusion at 375 milligrams per square meter (mg/m^2) body surface area dose q3w.
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Participants will receive escalating intravenous dose of polatuzumab vedotin.
Andra namn:
Rituximab will be administered by an IV infusion at 375 mg/m^2 body surface area dose q3w.
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
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Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Tidsram: Cycle 1 (Days 1-21)
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Cycle 1 (Days 1-21)
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Maximum Tolerated Dose
Tidsram: Cycle 1 (Days 1-21)
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Cycle 1 (Days 1-21)
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Proposed Phase II Dose of Polatuzumab Vedotin
Tidsram: Cycle 1 (Days 1-21)
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Cycle 1 (Days 1-21)
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Percentage of Participants With Adverse Events (AEs)
Tidsram: Baseline up to 646 Days
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Baseline up to 646 Days
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Sekundära resultatmått
Resultatmått |
Tidsram |
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Percentage of Paticipants with Anti Therapeutic Antibodies (ATAs) Against Polatuzumab Vedotin
Tidsram: Preinfusion (0 hour) on Day 1 of Cycles 1, 2, 4, and at the treatment completion/early termination visit (up to 646 days)
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Preinfusion (0 hour) on Day 1 of Cycles 1, 2, 4, and at the treatment completion/early termination visit (up to 646 days)
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Progression Free Survival (PFS), as Assessed by Using Modified Response Criteria for Non-Hodgkin Lymphoma (NHL) or Chronic Lymphocytic Leukemia (CLL)
Tidsram: Baseline up to disease progression or death (Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug [up to 44.5 months])
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Baseline up to disease progression or death (Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug [up to 44.5 months])
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Percentage of Participants With Objective Response [Complete Response (CR) or Partial Response (PR)], as Assessed by Using Modified Response Criteria for NHL or CLL
Tidsram: Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug (up to 44.5 months)
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Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug (up to 44.5 months)
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Duration of Response, as Assessed by Using Modified Response Criteria for NHL or CLL
Tidsram: Baseline up to disease progression or death (Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug [up to 44.5 months])
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Baseline up to disease progression or death (Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug [up to 44.5 months])
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Percentage of Participants with Best Overall Response (BOR), as Assessed by Using Modified Response Criteria for NHL or CLL
Tidsram: Baseline up to disease progression or death (Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug [up to 44.5 months])
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Baseline up to disease progression or death (Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug [up to 44.5 months])
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Area Under the Curve (AUC) from Time 0 to The Last Quantifiable Time Point (AUClast)-Polatuzumab Vedotin Monotherapy
Tidsram: Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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AUC Extrapolating to Time of Infinity (AUCinf)-Polatuzumab Vedotin Monotherapy
Tidsram: Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Percentage of AUCinf (AUCextrap)-Polatuzumab Vedotin Monotherapy
Tidsram: Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Maximum Plasma Concentration (Cmax)-Polatuzumab Vedotin Monotherapy
Tidsram: Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Clearance-Polatuzumab Vedotin Monotherapy
Tidsram: Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Volume of Distribution at Steady State-Polatuzumab Vedotin Monotherapy
Tidsram: Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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AUClast - Polatuzumab Vedotin Combined with Rituximab
Tidsram: Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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AUCinf-Polatuzumab Vedotin Combined with Rituximab
Tidsram: Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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AUCextrap-Polatuzumab Vedotin Combined with Rituximab
Tidsram: Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Cmax-Polatuzumab Vedotin Combined with Rituximab
Tidsram: Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Clearance-Polatuzumab Vedotin Combined with Rituximab
Tidsram: Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Volume of Distribution at Steady State-Polatuzumab Vedotin Combined with Rituximab
Tidsram: Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days)
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AUClast of Rituximab When Given in Combination With Polatuzumab Vedotin
Tidsram: Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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AUCinf of Rituximab When Given in Combination With Polatuzumab Vedotin
Tidsram: Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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AUCextrap of Rituximab When Given in Combination With Polatuzumab Vedotin
Tidsram: Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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Cmax of Rituximab When Given in Combination With Polatuzumab Vedotin
Tidsram: Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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Clearance of Rituximab When Given in Combination With Polatuzumab Vedotin
Tidsram: Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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Volume of Distribution at Steady State-of Rituximab When Given in Combination With Polatuzumab Vedotin
Tidsram: Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days)
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Studierektor: Yu-Waye Chu, M.D., Genentech, Inc.
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.
- Lu T, Gibiansky L, Li X, Li C, Shi R, Agarwal P, Hirata J, Miles D, Chanu P, Girish S, Jin JY, Lu D. Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2020 Dec;61(12):2905-2914. doi: 10.1080/10428194.2020.1795154. Epub 2020 Jul 24.
- Palanca-Wessels MC, Czuczman M, Salles G, Assouline S, Sehn LH, Flinn I, Patel MR, Sangha R, Hagenbeek A, Advani R, Tilly H, Casasnovas O, Press OW, Yalamanchili S, Kahn R, Dere RC, Lu D, Jones S, Jones C, Chu YW, Morschhauser F. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Lancet Oncol. 2015 Jun;16(6):704-15. doi: 10.1016/S1470-2045(15)70128-2. Epub 2015 Apr 27.
Användbara länkar
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
22 mars 2011
Primärt slutförande (Faktisk)
29 juni 2012
Avslutad studie (Faktisk)
18 november 2014
Studieregistreringsdatum
Först inskickad
3 februari 2011
Först inskickad som uppfyllde QC-kriterierna
4 februari 2011
Första postat (Uppskatta)
7 februari 2011
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
16 juni 2017
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
14 juni 2017
Senast verifierad
1 juni 2017
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Immunsystemets sjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Lymfoproliferativa störningar
- Lymfatiska sjukdomar
- Immunproliferativa störningar
- Leukemi, B-cell
- Lymfom
- Lymfom, B-cell
- Leukemi
- Lymfom, icke-Hodgkin
- Leukemi, lymfocytisk, kronisk, B-cell
- Leukemi, lymfoid
- Läkemedels fysiologiska effekter
- Antireumatiska medel
- Antineoplastiska medel
- Immunologiska faktorer
- Antineoplastiska medel, immunologiska
- Rituximab
Andra studie-ID-nummer
- DCS4968g
- GO01294 (Annan identifierare: Hoffmann-La Roche)
- 2011-002330-39 (EudraCT-nummer)
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Ja
Studerar en amerikansk FDA-reglerad produktprodukt
Nej
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .