Clinical trial NCT02453087: A Study of Escalating Doses of DCDS0780A in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Hodgkin's Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-05-25
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: Baseline up to 30 days after the last dose of study drug (up to 1 year)
measure: Percentage of Participants with Dose-Limiting Toxicities
timeFrame: Days 1 to 21
measure: Maximum Tolerated Dose (MTD) of DCDS0780A
timeFrame: Days 1 to 21
measure: Recommended Phase 2 Dose (RP2D) of DCDS0780A
timeFrame: Days 1 to 21
Secondary outcomes:
measure: Area Under the Serum Concentration-Time Curve (AUC) for DCDS0780A Total Antibody
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Maximum Observed Serum Concentration (Cmax) for DCDS0780A Total Antibody
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Total Clearance (CL) of DCDS0780A Total Antibody
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Half-life (t1/2) of DCDS0780A Total Antibody
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Volume of Distribution Under Steady-State Conditions (Vss) of DCDS0780A Total Antibody
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Area Under the Plasma Concentration-Time Curve (AUC) for DCDS0780A Conjugate (Antibody-Conjugated Monomethyl Auristatin E [acMMAE])
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Maximum Observed Plasma Concentration (Cmax) for acMMAE
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Total Clearance (CL) of acMMAE
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Half-life (t1/2) of acMMAE
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Volume of Distribution Under Steady-State Conditions (Vss) of acMMAE
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Area Under the Plasma Concentration-Time Curve (AUC) for Unconjugated Monomethyl Auristatin E (MMAE)
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Maximum Observed Plasma Concentration (Cmax) for Unconjugated MMAE
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Total Clearance (CL) of Unconjugated MMAE
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Half-life (t1/2) of Unconjugated MMAE
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Volume of Distribution Under Steady-State Conditions (Vss) of Unconjugated MMAE
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Obinutuzumab Serum Concentration
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Rituximab Serum Concentration
timeFrame: Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
measure: Percentage of Participants with Anti-DCDS0780A Antibodies
timeFrame: Baseline up to 2 to 4 months after last dose (up to 16 months)
measure: Absolute Lymphocyte Count
timeFrame: 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)
measure: Change from Baseline in Intra-Patient Absolute Lymphocyte Counts
timeFrame: 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)
measure: Time to CD19+ B-Cell Count Recovery to Baseline Value
timeFrame: 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)
measure: Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) Assessed According to Lugano Classification
timeFrame: 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)
measure: Duration of Response Assessed According to Lugano Classification
timeFrame: 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)
measure: Progression-Free Survival (PFS) Assessed According to Lugano Classification
timeFrame: 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)
measure: Relative Dose Intensity (DI) Calculated as Ratio of Amount of Drug Actually Administered to the Amount Planned
timeFrame: Baseline up to 1 year
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: Medical Center of Aurora; Rocky Mountain Cancer Centers
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center Lombardi Cancer Center
state: District of Columbia
city: Sarasota
country: United States
facility: Florida Cancer Specialists - Sarasota (North Catttlemen Rd)
state: Florida
city: New York
country: United States
facility: New York University Cancer Cen
state: New York
city: Eugene
country: United States
facility: Willamette Valley Cancer Ctr - 520 Country Club
state: Oregon
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: