- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT01307267
A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab
keskiviikko 4. maaliskuuta 2020 päivittänyt: Pfizer
A PHASE 1 STUDY OF PF-05082566 AS A SINGLE AGENT IN PATIENTS WITH ADVANCED CANCER, AND IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA (NHL)
A study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL).
Tutkimuksen yleiskatsaus
Tila
Valmis
Ehdot
Interventio / Hoito
Opintotyyppi
Interventio
Ilmoittautuminen (Todellinen)
190
Vaihe
- Vaihe 1
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Victoria
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Melbourne, Victoria, Australia, 3000
- Peter MacCallum Cancer Centre
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BO
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Bologna, BO, Italia, 40138
- Az. Ospedaliera-Univer. di Bologna Policlinico S. Orsola Malpighi
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MI
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Milano, MI, Italia, 20132
- Ospedale San Raffaele di Milano
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Akita, Japani, 010-8543
- Akita University Hospital
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Tokyo, Japani, 135-8550
- The Cancer Institute Hospital of Japanese Foundation for Cancer Research
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Chiba
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Kashiwa, Chiba, Japani, 277-8577
- National Cancer Center Hospital East
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RENNES cedex 9, Ranska, 35033
- Centre d'Investigation Clinique
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California
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Duarte, California, Yhdysvallat, 91010
- City of Hope
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La Jolla, California, Yhdysvallat, 92093
- UC San Diego Moores Cancer Center
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La Jolla, California, Yhdysvallat, 92037-0845
- UC San Diego Moores Cancer Center-Investigational Drug Services
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La Jolla, California, Yhdysvallat, 92037
- UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Hospital)
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Los Angeles, California, Yhdysvallat, 90095
- Ronald Reagan UCLA Medical Center, Drug Information Center
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Los Angeles, California, Yhdysvallat, 90095
- UCLA Hematology-Oncology Clinic
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Los Angeles, California, Yhdysvallat, 90095
- Research Administration Office: Clinical Research Unit
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Los Angeles, California, Yhdysvallat, 90095
- UCLA Bowyer Clinic
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Palo Alto, California, Yhdysvallat, 94304
- Stanford University Medical Center
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Palo Alto, California, Yhdysvallat, 94305
- Stanford University Medical Center
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San Diego, California, Yhdysvallat, 92103
- UC San Diego Medical Center - Hillcrest
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Santa Monica, California, Yhdysvallat, 90404
- Santa Monica UCLA Hematology & Oncology Clinic
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Stanford, California, Yhdysvallat, 94305
- Stanford University Medical Center
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District of Columbia
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Washington, District of Columbia, Yhdysvallat, 20007
- MedStar Georgetown University Hospital
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Washington, District of Columbia, Yhdysvallat, 20007
- Georgetown University Medical Center Department of Pharmacy, Research
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Georgia
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Atlanta, Georgia, Yhdysvallat, 30322
- Emory University Hospital
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Atlanta, Georgia, Yhdysvallat, 30308
- Emory University Hospital Midtown
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Atlanta, Georgia, Yhdysvallat, 30322
- The Emory Clinic
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Atlanta, Georgia, Yhdysvallat, 30322
- Winship Cancer Institute
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Atlanta, Georgia, Yhdysvallat, 30322
- The Emory Clinic, Building A
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Massachusetts
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Boston, Massachusetts, Yhdysvallat, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, Yhdysvallat, 02115
- Brigham and Woman's Hospital
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Michigan
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Ann Arbor, Michigan, Yhdysvallat, 48109
- University of Michigan Health System
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Missouri
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Creve Coeur, Missouri, Yhdysvallat, 63141
- Siteman Cancer Center-West County
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Saint Louis, Missouri, Yhdysvallat, 63110
- Washington University School of Medicine
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Saint Louis, Missouri, Yhdysvallat, 63110
- Barnes-Jewish Hospital
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Saint Louis, Missouri, Yhdysvallat, 63110
- Washington University Infusion Center Pharmacy
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Saint Louis, Missouri, Yhdysvallat, 63110-1094
- Barnes-Jewish Hospital
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Saint Louis, Missouri, Yhdysvallat, 63129
- Siteman Cancer Center- South County
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Saint Peters, Missouri, Yhdysvallat, 63376
- Siteman Cancer Center - St. Peters
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New York
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New York, New York, Yhdysvallat, 10065
- Memorial Sloan Kettering Cancer Center
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Texas
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Houston, Texas, Yhdysvallat, 77030
- The University of Texas - M.D. Anderson Cancer Center
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San Antonio, Texas, Yhdysvallat, 78229
- South Texas Accelerated Research Therapeutics, LLC
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Washington
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Seattle, Washington, Yhdysvallat, 98109
- Seattle Cancer Care Alliance
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Seattle, Washington, Yhdysvallat, 98195
- University of Washington Medical Center
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
18 vuotta ja vanhemmat (Aikuinen, Vanhempi Aikuinen)
Hyväksyy terveitä vapaaehtoisia
Ei
Sukupuolet, jotka voivat opiskella
Kaikki
Kuvaus
Inclusion Criteria
- Portion A: Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy or B cell lymphoma, for which no curative therapy is available. Portion A expansion includes patients who have documented disease progression on a checkpoint inhibitor (anti CTLA 4, anti PD1/PD L1 antibodies) per RECIST criteria. Tumor types include metastatic melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NCSLC) and squamous cell carcinoma of the head and neck (SCCHN). Patients in the dose expansion stage are required to provide archival or baseline (obtained during the screening period) tumor biopsies.
- Portion B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available. Patients enrolled in the expansion cohort must have archival tissue available, sampled within 6 months of study entry. The Expansion cohort includes patients with FL or DLBCL with relapsed or refractory disease.
- Measurable disease with at least one extranodal tumor mass >1.0 cm in the greatest transverse diameter (GTD) or in the case of malignant lymph nodes >1.5 cm in the GTD.
- ECOG performance status of ≤ 1.
- Adequate bone marrow function, for Portion A: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥100 x 109/L, hemoglobin >9.0 g/dL. For Portion B: ANC ≥ 1.0 x 109/L, platelet count ≥ 75 x 109/L, and hemoglobin ≥ 8.0 g/dL. In both cases, patients must be transfusion independent at least 14 days prior to screening.
- Serum creatinine ≤ 2 x ULN or estimated creatinine clearance ≥ 50 ml/min.
- Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome and AST and ALT ≤ 2.5 x ULN.
Exclusion Criteria
- Patients with known symptomatic brain metastases requiring steroids.
- Prior allogeneic hematopoietic stem cell transplant.
- Immunosuppressive regimens involving systemic corticosteroids within 14 days before the first dose of study treatment.
- Therapeutic or experimental monoclonal antibodies within 28 day or prior radiation therapy within 14 days of the first dose of study drug.
- Autoimmune disorders and other diseases that compromise or impair the immune system.
- Unstable or serious concurrent medical conditions in the previous 6 months.
- Prior therapy with any anti CD137 monoclonal antibody.
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: Portion A
PF-05082566 single agent in patients with advanced cancer
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Intravenous, Dose escalation, once per month
IV, Dose escalation, once per month
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Kokeellinen: Portion B
PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
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Intravenous, Dose escalation, once per month
IV, Dose escalation, once per month
Intravenous, 375 mg/m2, once per week for 4 weeks
Muut nimet:
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A
Aikaikkuna: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
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DLT: Any of the following adverse events (AEs) occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 alone for Portion A and not related to progressive disease.
Hematologic: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis.
Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT).
Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Each cycle=28 days.
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Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
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Number of Participants With DLTs in First 2 Cycles of Portion B
Aikaikkuna: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
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DLT: Any of the following AEs occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 in combination with rituximab for Portion B and not related to progressive disease.
Hematologic: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis.
Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT).
Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Each cycle=28 days.
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Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
---|---|---|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A
Aikaikkuna: Up to approximately 2 years
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
AEs included both non-serious AEs and SAEs.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Causality of AEs was determined by the investigator.
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Up to approximately 2 years
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Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A
Aikaikkuna: Up to approximately 2 years
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
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Up to approximately 2 years
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Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Aikaikkuna: Up to approximately 2 years
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Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells.
The abnormalities with at least 1 participant are presented here.
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Up to approximately 2 years
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Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Aikaikkuna: Up to approximately 2 years
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Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia.
The abnormalities with at least 1 participant are presented here.
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Up to approximately 2 years
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Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A
Aikaikkuna: Up to approximately 2 years
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For vital signs in Portion A, blood pressure and pulse rate were measured.
Clinical significance was determined by the investigator.
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Up to approximately 2 years
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PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A
Aikaikkuna: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose
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Cmax of PF-05082566 was observed directly from data.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose
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PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A
Aikaikkuna: Day 1 pre-dose of Cycle 2
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Ctrough of PF-05082566 was observed directly from data.
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Day 1 pre-dose of Cycle 2
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PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A
Aikaikkuna: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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Tmax of PF-05082566 was observed directly from data as time of Cmax.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 Area Under the Serum Concentration-Time Profile (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUClast) in Portion A
Aikaikkuna: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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AUClast of PF-05082566 was determined by linear/log trapezoidal method.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A
Aikaikkuna: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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AUCinf = AUClast + (Clast*/kel), where Clast* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A
Aikaikkuna: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 Clearance (CL) in Portion A
Aikaikkuna: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2. It was reported in units of milliliter per hour per kilogram (mL/hr/kg).
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A
Aikaikkuna: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A
Aikaikkuna: Up to approximately 2 years
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ADA for PF-05082566 was detected using electrochemiluminescence assay.
Positive ADA for PF-05082566: titer>=6.23.
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Up to approximately 2 years
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Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A
Aikaikkuna: Up to approximately 2 years
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Categorical summarization criteria for QTc interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate): 1) absolute value of >450 to <=480 milliseconds (msec), >480 to <=500 msec, >500 msec; 2) a maximum change from baseline of >30 to <=60 msec or >60 msec.
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Up to approximately 2 years
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Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A
Aikaikkuna: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Objective response: confirmed best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST version 1.1.
BOR of CR: target lesions and non-target diseases achieved CR, without new lesions.
BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-progression of disease (non-PD), indeterminate or missing, and without new lesions.
For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and >=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Duration of Response in Portion A
Aikaikkuna: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Duration of response: the time from first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1) to the date of first documentation of objective progression of disease (PD) or death due to any cause.
Objective PD per RECIST version 1.1: >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 millimeters (mm); or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
This outcome measure reports the individual values for evaluable participants (instead of medians etc) due to the limited number of events.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Time to Response in Portion A
Aikaikkuna: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Time to response: the time from Cycle 1 Day 1 to the first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1).
BOR of CR: target lesions and non-target diseases achieved CR, without new lesions.
BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-PD, indeterminate or missing, and without new lesions.
For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes decreased to normal size); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and >=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Progression-Free Survival in Portion A
Aikaikkuna: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Progression-free survival: the time from Cycle 1 Day 1 to the date of the first documentation of objective PD or death due to any cause, whichever occurred first.
Objective PD per RECIST version 1.1: >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm; or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Overall Survival in Portion A
Aikaikkuna: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Number of Participants With Treatment-Emergent AEs and SAEs in Portion B
Aikaikkuna: Up to approximately 4 years
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
AEs included both non-serious AEs and SAEs.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Causality of AEs was determined by the investigator.
|
Up to approximately 4 years
|
Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B
Aikaikkuna: Up to approximately 4 years
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
|
Up to approximately 4 years
|
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
Aikaikkuna: Up to approximately 2 years
|
Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells.
The abnormalities with at least 1 participant are presented here.
|
Up to approximately 2 years
|
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
Aikaikkuna: Up to approximately 2 years
|
Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia.
The abnormalities with at least 1 participant are presented here.
|
Up to approximately 2 years
|
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B
Aikaikkuna: Up to approximately 2 years
|
For vital signs in Portion B, blood pressure, pulse rate, and body temperature were measured.
Clinical significance was determined by the investigator.
|
Up to approximately 2 years
|
PF-05082566 Cmax in Portion B
Aikaikkuna: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
Cmax of PF-05082566 was observed directly from data.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
PF-05082566 Ctrough in Portion B
Aikaikkuna: Day 1 pre-dose of Cycle 2
|
Ctrough of PF-05082566 was observed directly from data.
|
Day 1 pre-dose of Cycle 2
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PF-05082566 Tmax in Portion B
Aikaikkuna: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
Tmax of PF-05082566 was observed directly from data as time of Cmax.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
PF-05082566 AUClast in Portion B
Aikaikkuna: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
AUClast of PF-05082566 was determined by linear/log trapezoidal method.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
PF-05082566 AUCinf in Portion B
Aikaikkuna: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
|
AUCinf = AUClast + (Clast*/kel), where Clast* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
|
PF-05082566 AUCtau in Portion B
Aikaikkuna: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
PF-05082566 CL in Portion B
Aikaikkuna: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
PF-05082566 Vss in Portion B
Aikaikkuna: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
Rituximab Cmax and Ctrough in Portion B
Aikaikkuna: Day 1 pre-dose of Cycle 2
|
Cmax and Ctrough of rituximab were observed directly from data.
|
Day 1 pre-dose of Cycle 2
|
Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B
Aikaikkuna: Up to approximately 2 years
|
ADA for PF-05082566 and rituximab was detected using electrochemiluminescence assay.
Positive ADA for PF-05082566: titer>=6.23.
Positive ADA for rituximab: titer>=1.88.
|
Up to approximately 2 years
|
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B
Aikaikkuna: Up to approximately 2 years
|
Categorical summarization criteria for QTc interval: 1) absolute value of >450 to <=480 milliseconds (msec), >480 to <=500 msec, >500 msec; 2) a maximum change from baseline of >30 to <=60 msec or >60 msec.
|
Up to approximately 2 years
|
Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B
Aikaikkuna: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Objective Response in Portion B was defined as BOR of CR or PR according to Cheson 2007 criteria.
BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or >=50% decrease in the sum of the product diameters [SPD] of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion >=15 mm in greatest transverse diameter [GTD], unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Duration of Response in Portion B
Aikaikkuna: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Duration of Response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from first documentation of objective response to the date of first documentation of objective PD or death due to any cause.
Objective PD per Cheson 2007 was defined as: PD of index lesions (>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Time to Response in Portion B
Aikaikkuna: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Time to response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from Cycle 1 Day 1 to the first documentation of objective response.
BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or >=50% decrease in the SPD of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Progression-Free Survival in Portion B
Aikaikkuna: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Progression-free survival in Portion B was defined as the time from Cycle 1 Day 1 to the date of the first documentation of objective PD (per Cheson 2007) or death due to any cause, whichever occurred first.
Objective PD per Cheson 2007 was defined as: PD of index lesions (>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Overall Survival in Portion B
Aikaikkuna: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
---|---|---|
Biomarkers Linked With Immunomodulation and Cytokine Release
Aikaikkuna: Days 1, 14, 29 and 57
|
This was an exploratory endpoint and no data were collected.
|
Days 1, 14, 29 and 57
|
Exploratory Pharmacodynamic Biomarkers
Aikaikkuna: Days 1 and 21
|
This was an exploratory endpoint and no data were collected.
|
Days 1 and 21
|
Patient-Reported Outcomes of PF-05082566 and Rituximab When Given in Combination in Follicular Lymphoma Participants
Aikaikkuna: Up to 2 years
|
This was an exploratory endpoint and was not evaluated.
Patient-reported outcome questionnaires were not completed as a result of administrative processing error.
|
Up to 2 years
|
Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Julkaisuja ja hyödyllisiä linkkejä
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Yleiset julkaisut
- Gopal AK, Levy R, Houot R, Patel SP, Popplewell L, Jacobson C, Mu XJ, Deng S, Ching KA, Chen Y, Davis CB, Huang B, Fly KD, Thall A, Woolfson A, Bartlett NL. First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas. Clin Cancer Res. 2020 Jun 1;26(11):2524-2534. doi: 10.1158/1078-0432.CCR-19-2973. Epub 2020 Mar 6.
- Segal NH, He AR, Doi T, Levy R, Bhatia S, Pishvaian MJ, Cesari R, Chen Y, Davis CB, Huang B, Thall AD, Gopal AK. Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer. Clin Cancer Res. 2018 Apr 15;24(8):1816-1823. doi: 10.1158/1078-0432.CCR-17-1922. Epub 2018 Mar 16.
Hyödyllisiä linkkejä
Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Tiistai 21. kesäkuuta 2011
Ensisijainen valmistuminen (Todellinen)
Keskiviikko 20. helmikuuta 2019
Opintojen valmistuminen (Todellinen)
Keskiviikko 20. helmikuuta 2019
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Maanantai 28. helmikuuta 2011
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Maanantai 28. helmikuuta 2011
Ensimmäinen Lähetetty (Arvio)
Keskiviikko 2. maaliskuuta 2011
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Tiistai 17. maaliskuuta 2020
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Keskiviikko 4. maaliskuuta 2020
Viimeksi vahvistettu
Sunnuntai 1. maaliskuuta 2020
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
- Hengityselinten sairaudet
- Immuunijärjestelmän sairaudet
- Neoplasmat histologisen tyypin mukaan
- Neoplasmat
- Lymfoproliferatiiviset häiriöt
- Lymfaattiset sairaudet
- Immunoproliferatiiviset häiriöt
- Keuhkosairaudet
- Urologiset kasvaimet
- Urogenitaaliset kasvaimet
- Neoplasmat sivustoittain
- Munuaissairaudet
- Urologiset sairaudet
- Adenokarsinooma
- Kasvaimet, rauhas- ja epiteelikasvaimet
- Hengitysteiden kasvaimet
- Rintakehän kasvaimet
- Syöpä, bronkogeeninen
- Keuhkoputkien kasvaimet
- Pään ja kaulan kasvaimet
- Neuroektodermaaliset kasvaimet
- Neoplasmat, sukusolut ja alkiot
- Kasvaimet, hermokudos
- Munuaisten kasvaimet
- Keuhkojen kasvaimet
- Neuroendokriiniset kasvaimet
- Nevi ja melanoomat
- Kasvaimet, okasolusolut
- Lymfooma, B-solu
- Lymfooma
- Lymfooma, follikulaarinen
- Lymfooma, suuri B-solu, diffuusi
- Karsinooma, munuaissolut
- Karsinooma, ei-pienisoluinen keuhko
- Karsinooma
- Lymfooma, non-Hodgkin
- Melanooma
- Karsinooma, okasolusolu
- Pään ja kaulan okasolusyöpä
- Huumeiden fysiologiset vaikutukset
- Reumaattiset aineet
- Antineoplastiset aineet
- Immunologiset tekijät
- Antineoplastiset aineet, immunologiset
- Rituksimabi
- Vasta-aineet, monoklonaaliset
- Immunoglobuliini G
Muut tutkimustunnusnumerot
- B1641001
- 2011-002799-17 (EudraCT-numero)
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
EI
IPD-suunnitelman kuvaus
Pfizer will provide access to individual de-identified participant data and related study documents (e.g.
protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.
Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .
Kliiniset tutkimukset PF-05082566
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M.D. Anderson Cancer CenterPfizer; ISA Pharmaceuticals B.V.ValmisSuun nielun syöpä | Pahanlaatuiset kasvaimet huonosti määritellyissä toissijaisissa ja määrittelemättömissä paikoissa | Huulen suuontelon ja nielun pahanlaatuiset kasvaimetYhdysvallat
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PfizerValmisNeoplasmatYhdysvallat, Alankomaat, Ranska, Japani
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PfizerLopetettuPitkälle edennyt syöpäYhdysvallat, Kanada, Yhdistynyt kuningaskunta, Taiwan, Australia, Ranska, Japani, Puola
-
PfizerMerck Sharp & Dohme LLCValmisEdistyneet kiinteät kasvaimetYhdysvallat
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Aktiivinen, ei rekrytointiPahanlaatuinen kiinteä kasvain | Edistynyt pahanlaatuinen kiinteä kasvain | Tulenkestävä pahanlaatuinen kiinteä kasvain | Kastraatioresistentti eturauhassyöpä | Metastaattinen eturauhassyöpä | IV vaiheen eturauhassyöpä AJCC v8 | Metastaattinen pahanlaatuinen kiinteä kasvain | IVA-vaiheen eturauhassyöpä... ja muut ehdotYhdysvallat
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William Beaumont HospitalsValmisVerenmenetys, kirurginen | Intraoperatiiviset komplikaatiot | Komplikaatiot; Nivelleikkaus | OlkanivelsairausYhdysvallat
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Hope Rugo, MDJohns Hopkins University; Pfizer; Gilead Sciences; Hoosier Cancer Research Network ja muut yhteistyökumppanitRekrytointiIV vaiheen rintasyöpä | Toistuva rintasyöpä | Vaiheen IIIA rintasyöpä | Vaiheen IIIB rintasyöpä | Invasiivinen rintasyöpä | Ei leikattava rintasyöpä | Vaiheen IIIC rintasyöpä | Kolminkertainen negatiivinen rintasyöpä | Vaiheen III rintasyöpäYhdysvallat
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Aktiivinen, ei rekrytointiMetastaattinen kolorektaalinen karsinooma | IV-vaiheen kolorektaalisyöpä AJCC v8 | IVA-vaiheen kolorektaalisyöpä AJCC v8 | IVB-vaiheen kolorektaalisyöpä AJCC v8 | IVC-vaiheen kolorektaalisyöpä AJCC v8Yhdysvallat
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PfizerValmis
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PfizerValmis