A Study of Pinatuzumab Vedotin (DCDT2980S) Combined With Rituximab or Polatuzumab Vedotin (DCDS4501A) Combined With Rituximab or Obinutuzumab in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL)
ROMULUS
A Randomized, Open-Label, Multicenter, Phase II Trial Evaluating the Safety and Activity of Pinatuzumab Vedotin (DCDT2980S) in Combination With Rituximab or Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab and a Non-Randomized Phase Ib/II Evaluation of Polatuzumab Vedotin in Combination With Obinutuzumab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
2 other identifiers
interventional
231
6 countries
41
Brief Summary
This multicenter, open-label study will evaluate the safety and efficacy of pinatuzumab vedotin (DCDT2980S) or polatuzumab vedotin (DCDS4501A) in combination with rituximab (RTX), as well as of polatuzumab vedotin in combination with obinutuzumab in participants with relapsed or refractory (r/r) follicular lymphoma (FL) and r/r diffuse large B-cell lymphoma (DLBCL).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2012
Longer than P75 for phase_1
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 16, 2012
CompletedFirst Posted
Study publicly available on registry
September 25, 2012
CompletedStudy Start
First participant enrolled
September 27, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 8, 2017
CompletedResults Posted
Study results publicly available
April 19, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
February 7, 2019
CompletedFebruary 21, 2020
February 1, 2020
4.4 years
September 16, 2012
March 6, 2018
February 20, 2020
Conditions
Outcome Measures
Primary Outcomes (3)
Percentage of Participants With a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments greater than or equal to (\>/=) 4 weeks after initial documentation. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as \>/=50 percent (%) decrease in sum of the products of greatest diameters (SPD) of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a \>/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. Participants with insufficient data to determine response were classified as non-responders.
Baseline up to 12 months after the last dose of study treatment (up to approximately 3.5 years)
Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014). DOR was defined as the time from the initial documentation of a CR or PR to the time of PD or death. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as \>/=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a \>/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. PD was defined as appearance of any new lesion more than 1.5 centimeters (cm) in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.
First occurrence of objective response up to PD/relapse or death due to any cause, whichever occurred first (up to approximately 3.5 years)
Percentage of Participants With CR at End of Treatment (EOT) Based on Positron Emission Tomographic/Computed Tomography (PET/CT) Assessment Determined by Independent Review Committee (IRC) Per Lugano 2014 Response Criteria: Cohorts E, G, and H
Tumor response assessment was performed by an IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to \[\</=\] mediastinum), or 3 (uptake less than \[\<\] mediastinum but \</=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method.
6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Secondary Outcomes (49)
Number of Participants With Anti-Drug Antibodies (ADA) to Pinatuzumab Vedotin
Baseline, post-baseline (up to approximately 5.5 years)
Number of Participants With ADA to Polatuzumab Vedotin
Baseline, post-baseline (up to approximately 5.5 years)
Number of Participants With ADA to Obinutuzumab
Baseline, post-baseline (up to approximately 5.5 years)
Percentage of Participants With PD as Determined by Modified Response and Progression Criteria for NHL or Death Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)
Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years)
Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years)
- +44 more secondary outcomes
Study Arms (6)
Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab
EXPERIMENTALFor the first 2 cycles, RTX 375 milligrams per square meter (mg/m\^2) will be given by intravenous (IV) infusion on Day 1 and pinatuzumab vedotin 2.4 milligrams per kilogram (mg/kg) will be administered by IV infusion on Day 2 to Arm A participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and pinatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop disease progression (PD) will be further treated with RTX 375 mg/m\^2 followed by polatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).
Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab
EXPERIMENTALFor the first 2 cycles, RTX 375 mg/m\^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 2.4 mg/kg will be administered by IV infusion on Day 2 to Arm B participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop PD would be further treated with RTX 375 mg/m\^2 followed by pinatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).
Cohort C (FL): RTX + Polatuzumab
EXPERIMENTALFor the first 2 cycles, RTX 375 mg/m\^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 1.8 mg/kg will be administered by IV infusion on Day 2 to Cohort C participants (with r/r FL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, PD, or withdrawal from study.
Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab
EXPERIMENTALFor the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort E participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.
Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab
EXPERIMENTALFor the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort G participants (with r/r FL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort G participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.
Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
EXPERIMENTALFor the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort H participants (with r/r DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort H participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.
Interventions
Obinutuzumab 1000 mg will be administered by IV infusion on Days 1, 8, 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.
Pinatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.
Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.
RTX 375 mg/m\^2 administered by IV infusion on Day 1 of every 21-day cycle.
Eligibility Criteria
You may qualify if:
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Life expectancy of at least 12 weeks
- History of histologically documented r/r Grades 1 to 3a FL, or r/r DLBCL
- Availability of an archival or freshly biopsied tumor tissue sample must be confirmed for study enrollment
- Have a clinical indication for treatment as determined by the investigator
- Must have at least one bi-dimensionally measurable lesion (greater than \[\>\] 1.5 centimeters \[cm\] in its largest dimension by CT scan or Magnetic Resonance Imaging \[MRI\])
You may not qualify if:
- Prior use of any monoclonal antibody, radio-immuno-conjugate or antibody drug conjugate within 4 weeks before study start
- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational anti-cancer agent within 2 weeks prior study start
- Adverse events except for sensory neuropathy from any previous treatments must be resolved or stabilized to Grade less than equal to (\</=) 2 prior study start
- Completion of autologous stem cell transplant (SCT) within 100 days prior study start
- Prior allogeneic SCT
- Eligibility for autologous SCT (participants with r/r DLBCL)
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- Current or past history of central nervous system lymphoma
- Current Grade \>1 peripheral neuropathy
- Vaccination with a live vaccine within 28 days prior to treatment
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
Study Sites (41)
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
Stanford Cancer Center
Stanford, California, 94305-5820, United States
Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
Denver, Colorado, 80218, United States
Georgetown University Medical Center Lombardi Cancer Center
Washington D.C., District of Columbia, 20007, United States
Florida Cancer Specialists - Fort Myers (Colonial Center Dr)
Fort Myers, Florida, 33905, United States
Florida Cancer Specialists; Sarasota
Sarasota, Florida, 34232, United States
Univ of Michigan Med School; Hematology Oncology
Ann Arbor, Michigan, 48109, United States
Comprehensive Cancer Centers of Nevada - Eastern Avenue
Las Vegas, Nevada, 89169, United States
Hematology Oncology Associates; Carol G. Simon Ctr
Morristown, New Jersey, 07960, United States
Regional Cancer Care Associates LLC - Morristown
Morristown, New Jersey, 07962, United States
Roswell Park Cancer Inst.
Buffalo, New York, 14263, United States
New York University Cancer Cen
New York, New York, 10016, United States
Oncology Hematology Care Inc
Cincinnati, Ohio, 45242, United States
Willamette Valley Cancer Ctr - 520 Country Club
Eugene, Oregon, 97401-8122, United States
Oregon Health Sciences Uni
Portland, Oregon, 97239, United States
Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
Nashville, Tennessee, 37203, United States
Texas Oncology-Baylor Sammons Cancer Center
Dallas, Texas, 75246, United States
Cancer Care Centers of South Texas
San Antonio, Texas, 78217, United States
Texas Transplant Inst.
San Antonio, Texas, 78229, United States
Texas Oncology, P.A. - Tyler; Tyler Cancer Center
Tyler, Texas, 75702, United States
Fairfax N Virginia Hem/Onc PC
Fairfax, Virginia, 22031, United States
Oncology & Hematolgy Associates of SW Va Inc. - Roanoke
Roanoke, Virginia, 24014, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Northwest Cancer Specialists - Vancouver
Vancouver, Washington, 98684, United States
Yakima Valley Memorial Hospital/North Star Lodge
Yakima, Washington, 98902, United States
Univ of Wisconsin-Madison
Madison, Wisconsin, 53705, United States
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
British Columbia Cancer Agency
Vancouver, British Columbia, V5Z 1H6, Canada
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
Montreal, Quebec, H3T 1E2, Canada
Hopital Claude Huriez - CHU Lille
Lille, 59037, France
CHU Montpellier - Saint ELOI
Montpellier, 34295, France
Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)
Paris, 75475, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495, France
Centre Henri Becquerel; Hematologie
Rouen, 76038, France
Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V
Heidelberg, 69120, Germany
Universitätsmedizin Johannes Gutenberg Universität; Klinik u. Poliklinik f. Neurologie
Mainz, 55131, Germany
Klinikum d.Universität München Campus Großhadern
München, 81377, Germany
A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
Bologna, Emilia-Romagna, 40138, Italy
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
Milan, Lombardy, 20133, Italy
Azienda Ospedale San Giovanni
Turin, Piedmont, 10126, Italy
Academisch Medisch Centrum; Hematologie
Amsterdam, 1105 AZ, Netherlands
Related Publications (3)
Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.
PMID: 32770353DERIVEDLu T, Gibiansky L, Li X, Li C, Shi R, Agarwal P, Hirata J, Miles D, Chanu P, Girish S, Jin JY, Lu D. Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2020 Dec;61(12):2905-2914. doi: 10.1080/10428194.2020.1795154. Epub 2020 Jul 24.
PMID: 32705923DERIVEDMorschhauser F, Flinn IW, Advani R, Sehn LH, Diefenbach C, Kolibaba K, Press OW, Salles G, Tilly H, Chen AI, Assouline S, Cheson BD, Dreyling M, Hagenbeek A, Zinzani PL, Jones S, Cheng J, Lu D, Penuel E, Hirata J, Wenger M, Chu YW, Sharman J. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol. 2019 May;6(5):e254-e265. doi: 10.1016/S2352-3026(19)30026-2. Epub 2019 Mar 29.
PMID: 30935953DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Genentech, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 16, 2012
First Posted
September 25, 2012
Study Start
September 27, 2012
Primary Completion
March 8, 2017
Study Completion
February 7, 2019
Last Updated
February 21, 2020
Results First Posted
April 19, 2018
Record last verified: 2020-02