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

NCT02453087 | Completed Phase 1 FDA Drug

• 1 other identifier: GO29687
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 7

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.

Conditions

Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (4)

• Number of Participants with Adverse Events

  Baseline up to 30 days after the last dose of study drug (up to 1 year)

• Percentage of Participants with Dose-Limiting Toxicities

  Days 1 to 21

• Maximum Tolerated Dose (MTD) of DCDS0780A

  Days 1 to 21

• Recommended Phase 2 Dose (RP2D) of DCDS0780A

  Days 1 to 21

Secondary Outcomes (25)

• Area Under the Serum Concentration-Time Curve (AUC) for DCDS0780A Total Antibody

  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

  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

  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

  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

  Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)

Study Arms (3)

DCDS0780A Monotherapy

EXPERIMENTAL

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).

Drug: DCDS0780A

DCDS0780A + Rituximab

EXPERIMENTAL

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).

Drug: DCDS0780A; Drug: Rituximab

DCDS0780A + Obinutuzumab

EXPERIMENTAL

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).

Drug: DCDS0780A; Drug: Obinutuzumab

Interventions

DCDS0780A DRUG

Participants will receive escalating doses of DCDS0780A as intravenous infusion.

DCDS0780A + Obinutuzumab; DCDS0780A + Rituximab; DCDS0780A Monotherapy

Rituximab DRUG

Participants will receive rituximab at a dose of 375 mg/m\^2 of body surface area as intravenous infusion.

Also known as: Rituxan®, MabThera®

DCDS0780A + Rituximab

Obinutuzumab DRUG

Participants will receive obinutuzumab at a dose of 1000 milligrams (mg) as intravenous infusion.

Also known as: GA101, Gazyva™, Gazyvaro™

DCDS0780A + Obinutuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (7)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford Cancer Center

Stanford, California, 94305-5820, United States

Location

Medical Center of Aurora; Rocky Mountain Cancer Centers

Aurora, Colorado, 80012, United States

Location

Georgetown University Medical Center Lombardi Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists - Sarasota (North Catttlemen Rd)

Sarasota, Florida, 34232, United States

Location

New York University Cancer Cen

New York, New York, 10016, United States

Location

Willamette Valley Cancer Ctr - 520 Country Club

Eugene, Oregon, 97401-8122, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Rituximab; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2015
• First Posted: May 25, 2015
• Study Start: August 4, 2015
• Primary Completion: July 12, 2019
• Study Completion: July 12, 2019
• Last Updated: August 29, 2019

Record last verified: 2019-08

Locations

US (7)