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A Study of Escalating Doses of DCDS0780A in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

27 de agosto de 2019 actualizado por: Hoffmann-La Roche

An Open-label, Multicenter, Phase 1/1b Dose Escalation Study Evaluating the Pharmacokinetics, Safety, Tolerability, and Preliminary Efficacy of DCDS0780A, Alone or in Combination With Rituximab, or Obinutuzumab, in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

This open-label, multicenter, Phase 1/1b study will evaluate the safety, tolerability, and pharmacokinetics of increasing doses of DCDS0780A in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma. In the combination portion of the study, the safety and tolerability of DCDS0780A in combination with rituximab or obinutuzumab will be assessed.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

66

Fase

  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Estados Unidos
    • California
      • Duarte, California, Estados Unidos, 91010
        • City of Hope National Medical Center
      • Stanford, California, Estados Unidos, 94305-5820
        • Stanford Cancer Center
    • Colorado
      • Aurora, Colorado, Estados Unidos, 80012
        • Medical Center of Aurora; Rocky Mountain Cancer Centers
    • District of Columbia
      • Washington, District of Columbia, Estados Unidos, 20007
        • Georgetown University Medical Center Lombardi Cancer Center
    • Florida
      • Sarasota, Florida, Estados Unidos, 34232
        • Florida Cancer Specialists - Sarasota (North Catttlemen Rd)
    • New York
      • New York, New York, Estados Unidos, 10016
        • New York University Cancer Cen
    • Oregon
      • Eugene, Oregon, Estados Unidos, 97401-8122
        • Willamette Valley Cancer Ctr - 520 Country Club

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Life expectancy of at least 12 weeks
  • Histologically confirmed B-cell non-Hodgkin's lymphoma that has relapsed after or failed to respond to at least one prior treatment regimen and for which no suitable therapy of curative intent or higher priority exists
  • A clinical indication for treatment as determined by the investigator
  • Availability of archival or freshly collected tumor tissue before study enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Fasting (greater than or equal to [>=] 8 hours) glucose less than or equal to (<=) 160 milligrams per deciliter (mg/dL)
  • Participants requiring anti-diabetic medications must be on a stable dose and regimen for >=4 weeks
  • Adequate hematologic function without growth factor or transfusion support
  • For women who are not postmenopausal (>= 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods as specified in protocol
  • For men: agreement to remain abstinent or use a condom plus an additional contraceptive method as specified in protocol

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, systemic steroids used as an anti-neoplastic agent, or any other investigational anti-cancer agent within 2 weeks prior to Cycle 1, Day 1
  • Completion of autologous stem cell transplant within 100 days prior to Cycle 1, Day 1
  • Prior allogeneic stem cell transplant
  • Current or history of CNS lymphoma
  • Current Grade greater than (>) 1 toxicity (except alopecia and anorexia) from prior therapy
  • Current Grade >1 peripheral neuropathy from any cause
  • Glycosylated hemoglobin (HbA1c) >=7.5 percent (%)
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
  • Prior irradiation to lung fields
  • Clinically significant pulmonary disease
  • Recent major surgery within 4 weeks prior to Cycle 1, Day 1, other than superficial lymph node biopsies for diagnosis
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Presence of positive test results for hepatitis B (hepatitis B surface antigen [HbsAg] and/or total hepatitis B core antibody [anti-HBc]) or hepatitis C (hepatitis C virus [HCV] antibody)
  • Known history of human immunodeficiency virus (HIV) seropositive status
  • Women who are pregnant or lactating or intending to become pregnant during the study
  • Any abnormal laboratory values as specified in protocol
  • Requirement for any excluded medication as specified in protocol
  • History of other malignancy that could affect compliance with the protocol or interpretation of results
  • 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 participant at high risk from treatment complications, including inadequately controlled diabetes or significant cardiovascular disease
  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1
  • Participants in Phase 1b Stage Only: Vaccination with live vaccines within 6 months before Cycle 1, Day 1

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: No aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: DCDS0780A Monotherapy
Participants will receive escalating doses of DCDS0780A as intravenous infusion as monotherapy on Day 1 of each 21-day cycle up to approximately 1 year or until disease progression or unacceptable toxicity (whichever comes first).
Droga: DCDS0780A
Participants will receive escalating doses of DCDS0780A as intravenous infusion.
Experimental: DCDS0780A + Rituximab
Participants will receive escalating doses of DCDS0780A on Day 2 of Cycles 1 and 2, and from Cycle 3 onwards on Day 1 of each 21-day cycle in combination with rituximab at a dose of 375 milligrams per square meter (mg/m^2) of body surface area as intravenous infusion on Day 1 of each 21-day cycle up to approximately 1 year or until disease progression or unacceptable toxicity (whichever comes first).
Droga: DCDS0780A
Participants will receive escalating doses of DCDS0780A as intravenous infusion.
Droga: Rituximab
Participants will receive rituximab at a dose of 375 mg/m^2 of body surface area as intravenous infusion.
Otros nombres:
  • Rituxan®
  • MabThera®
Experimental: DCDS0780A + Obinutuzumab
Participants will receive escalating doses of DCDS0780A on Day 2 of Cycles 1 and 2, and from Cycle 3 onwards on Day 1 of each 21-day cycle in combination with obinutuzumab at a dose of 1000 milligrams (mg) as intravenous infusion on Days 1, 8, and 15 of Cycle 1, and from Cycle 2 onwards on Day 1 of each 21-day cycle up to approximately 1 year or until disease progression or unacceptable toxicity (whichever comes first).
Droga: DCDS0780A
Participants will receive escalating doses of DCDS0780A as intravenous infusion.
Droga: Obinutuzumab
Participants will receive obinutuzumab at a dose of 1000 milligrams (mg) as intravenous infusion.
Otros nombres:
  • GA101
  • Gazyva®
  • Gazyvaro™

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Number of Participants with Adverse Events
Periodo de tiempo: Baseline up to 30 days after the last dose of study drug (up to 1 year)
Baseline up to 30 days after the last dose of study drug (up to 1 year)
Percentage of Participants with Dose-Limiting Toxicities
Periodo de tiempo: Days 1 to 21
Days 1 to 21
Maximum Tolerated Dose (MTD) of DCDS0780A
Periodo de tiempo: Days 1 to 21
Days 1 to 21
Recommended Phase 2 Dose (RP2D) of DCDS0780A
Periodo de tiempo: Days 1 to 21
Days 1 to 21

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Area Under the Serum Concentration-Time Curve (AUC) for DCDS0780A Total Antibody
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to end of treatment (ET) visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Maximum Observed Serum Concentration (Cmax) for DCDS0780A Total Antibody
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Total Clearance (CL) of DCDS0780A Total Antibody
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Half-life (t1/2) of DCDS0780A Total Antibody
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Volume of Distribution Under Steady-State Conditions (Vss) of DCDS0780A Total Antibody
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Area Under the Plasma Concentration-Time Curve (AUC) for DCDS0780A Conjugate (Antibody-Conjugated Monomethyl Auristatin E [acMMAE])
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Maximum Observed Plasma Concentration (Cmax) for acMMAE
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Total Clearance (CL) of acMMAE
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Half-life (t1/2) of acMMAE
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Volume of Distribution Under Steady-State Conditions (Vss) of acMMAE
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Area Under the Plasma Concentration-Time Curve (AUC) for Unconjugated Monomethyl Auristatin E (MMAE)
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Maximum Observed Plasma Concentration (Cmax) for Unconjugated MMAE
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Total Clearance (CL) of Unconjugated MMAE
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Half-life (t1/2) of Unconjugated MMAE
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Volume of Distribution Under Steady-State Conditions (Vss) of Unconjugated MMAE
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.

Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.

Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Obinutuzumab Serum Concentration
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 1; Cycle 1 Days 4 (or 5); Pre-infusion and 0.5 hours after end of infusion on Cycle 1 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 1; Pre-infusion and 0.5 hours after end of infusion on Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2, 4, 6 months after ET.

Pre-infusion = 0-4 hours before infusion; infusion rate = 50 milligrams per hour initially (to be adjusted in case of reactions), ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Rituximab Serum Concentration
Periodo de tiempo: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 1; Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 1; Pre-infusion and 0.5 hours after end of infusion on Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2, 4, 6 months after ET.

Pre-infusion = 0-4 hours before infusion; infusion rate = 50 milligrams per hour initially (to be adjusted in case of reactions), ET = 30 days after last dose (up to 1 year), cycle length = 21 days.
Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Percentage of Participants with Anti-DCDS0780A Antibodies
Periodo de tiempo: Baseline up to 2 to 4 months after last dose (up to 16 months)
Baseline up to 2 to 4 months after last dose (up to 16 months)
Absolute Lymphocyte Count
Periodo de tiempo: Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years)
Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years)
Change from Baseline in Intra-Patient Absolute Lymphocyte Counts
Periodo de tiempo: Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years)
Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years)
Time to CD19+ B-Cell Count Recovery to Baseline Value
Periodo de tiempo: Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years)
Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years)
Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) Assessed According to Lugano Classification
Periodo de tiempo: Baseline up to first occurrence of disease progression or death from any cause within 30 days after the last dose of study drug (up to 1 year)
Baseline up to first occurrence of disease progression or death from any cause within 30 days after the last dose of study drug (up to 1 year)
Duration of Response Assessed According to Lugano Classification
Periodo de tiempo: From the first occurrence of a documented objective response (CR or PR) to the time of relapse or death from any cause (up to 1 year)
From the first occurrence of a documented objective response (CR or PR) to the time of relapse or death from any cause (up to 1 year)
Progression-Free Survival (PFS) Assessed According to Lugano Classification
Periodo de tiempo: Baseline up to first occurrence of disease progression or death from any cause within 30 days after the last dose of study drug (up to 1 year)
Baseline up to first occurrence of disease progression or death from any cause within 30 days after the last dose of study drug (up to 1 year)
Relative Dose Intensity (DI) Calculated as Ratio of Amount of Drug Actually Administered to the Amount Planned
Periodo de tiempo: Baseline up to 1 year
Baseline up to 1 year

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Hoffmann-La Roche

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

4 de agosto de 2015

Finalización primaria (Actual)

12 de julio de 2019

Finalización del estudio (Actual)

12 de julio de 2019

Fechas de registro del estudio

Enviado por primera vez

21 de mayo de 2015

Primero enviado que cumplió con los criterios de control de calidad

21 de mayo de 2015

Publicado por primera vez (Estimar)

25 de mayo de 2015

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

29 de agosto de 2019

Última actualización enviada que cumplió con los criterios de control de calidad

27 de agosto de 2019

Última verificación

1 de agosto de 2019

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • GO29687

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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