Phase II Randomized Trial Comparing GA101 and Rituximab in Untreated Low Tumor Burden Indolent Non-Hodgkin's Lymphoma

NCT01889797 | Terminated Phase 2 Results DMC

• 2 other identifiers: PrE0401BO25454
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 28

Brief Summary

Patients with previously untreated low tumor burden indolent Non-Hodgkin's Lymphoma (NHL) will receive either rituximab or GA101 weekly for 4 weeks followed by re-staging to determine response. Rituximab, an anti-CD20 chimeric antibody, was approved by the United States Food and Drug Administration in 1998 for the treatment of patients with relapsed low-grade B-cell lymphomas. Clinically, four weekly doses of rituximab have proven to be well tolerated and effective in previously untreated as well as relapsed patients with low-grade lymphoma. GA101 is an anti-CD20 humanized and glyco-engineered monoclonal antibody. GA101 has been shown to have increased antibody-dependent cellular cytotoxicity (ADCC) and direct cell-death induction compared to Rituximab. It is possible that GA101 may have greater efficacy than rituximab. PrE0401 Sub-Study Evaluation of Corrected QT (QTc) Interval and Pharmacokinetic Parameters in Patients Participating in GA101 (Obinutuzumab) Approximately twenty-five patients randomized to GA101 may participate in the sub-study. Electrocardiograms and blood samples will be obtained.

Conditions

Indolent Non-Hodgkin's Lymphoma

Keywords

Untreated Non-Hodgkin's Lymphoma; Low Tumor Burden Non-Hodgkin's Lymphoma; NHL; Indolent; Rituximab; Rituxan; GA101; Obinutuzumab

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate

  Positron Emission Tomography (PET)-documented CR rates after induction therapy (weekly treatment x 4 weeks with GA101 or rituximab) Definitions for clinical response are modified from the Revised Response Criteria for Malignant Lymphoma (Cheson BD, et al. Revised Response Criteria for Malignant Lymphoma. J Clin Oncol 2007; 25(5): 579-86). Lymph node measurements were taken from CT, CT portion of the PET/CT, or MRI scans where applicable. CR is defined as complete disappearance of all evidence of disease; PR as a \>50% decrease in the sum of the products of the maximal perpendicular diameters of measured lesions (SPD) and no new sites; SD as failure to attain CR/PR or PD; and PD as any new lesion \>1.5cm in any axis or ≥50% increase in previously involved sites.

  Re-staging (week 12, 13 or 14) and during follow-up if physician feels patient is subsequently in CR for up to 4 years

Secondary Outcomes (3)

• PET Response Rate

  Re-staging (week 12, 13 or 14)

• Overall Response Rate

  Baseline and Re-staging (week 12, 13 or 14)

• Progression Free Survival (PFS)

  Percent of participants alive and progression-free at 1 year

Study Arms (2)

Arm A: Rituximab

ACTIVE COMPARATOR

Rituximab 375 mg/m² IV weekly for 4 weeks.

Biological: Arm A: Rituximab

Arm B: GA101

EXPERIMENTAL

GA101 1,000 mg IV weekly for 4 weeks.

Biological: Arm B: GA101

Interventions

Arm A: Rituximab BIOLOGICAL

Rituximab 375 mg/m² IV x 4 weekly doses.

Also known as: IDEC-C2B8, Chimeric anti-CD20 monoclonal antibody, Rituxan, NSC# 687451

Arm A: Rituximab

Arm B: GA101 BIOLOGICAL

GA101 1,000 mg (flat dose) IV x 4 weekly doses.

Also known as: Obinutuzumab, RO5072759, huMAB<CD20>

Arm B: GA101

Eligibility Criteria

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

You may qualify if:

• Registration: Patients having both diffuse and follicular architectural elements will be considered eligible if the histology is predominantly follicular (≥ 50% of the cross-sectional area), and there is no evidence of transformation to a large cell histology.
• Biopsy-proven diagnosis of Grade 1 or 2 follicular non-Hodgkin's lymphoma with no evidence of transformation to large cell histology.
• Meet criteria for Low Tumor Burden:
• No nodal or extra nodal mass ≥ 7 centimeter (cm)
• \<3 nodal masses \>3 cm in diameter
• No systemic symptoms or B symptoms
• No splenomegaly \>16 cm by CT scan
• No risk of compression of a vital organ.
• No leukemic phase with \>5000/mm³ circulating lymphocytes.
• No cytopenias defined as:
• Platelets \<100,000/mm³
• Hemoglobin (Hgb) \<10 g/dL
• Absolute Neutrophil Count (ANC) \<1500/mm³
• Must have Stage III or Stage IV disease.
• Baseline measurements/evaluations obtained within 6 weeks of registration. Patient must have at least one objective measurable disease parameter.

Sponsors & Collaborators

• PrECOG, LLC.: lead
• Genentech, Inc.: collaborator

Study Sites (28)

University of South Alabama

Mobile, Alabama, 36604, United States

Location

Marin Cancer Care

Greenbrae, California, 94904, United States

Location

St. Joseph's/Candler Health System

Savannah, Georgia, 31405, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Siouxland Hematology Oncology Associates

Sioux City, Iowa, 51101, United States

Location

Ochsner Cancer Institute

New Orleans, Louisiana, 70121, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

St. Joseph Mercy Health System

Ann Arbor, Michigan, 48106, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro MN CCOP

Saint Louis Park, Minnesota, 55416, United States

Location

Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Aultman Hospital

Canton, Ohio, 44710, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Toledo Community Oncology Program

Toledo, Ohio, 43617, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Susquehanna Health Cancer Center

Williamsport, Pennsylvania, 17701, United States

Location

University of Virginia

Charlottesburg, Virginia, 22908, United States

Location

Charleston Area Medical Center (CAMC)

Charleston, West Virginia, 25304, United States

Location

Gundersen Health System

La Crosse, Wisconsin, 54601, United States

Location

Dean Clinic

Madison, Wisconsin, 53717, United States

Location

ProHealth Care, Inc.

Waukesha, Wisconsin, 53188, United States

Location

Aurora Health Care

Wauwatosa, Wisconsin, 53266, United States

Location

Related Publications (5)

• Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. doi: 10.1200/JCO.2002.08.674.

  PMID: 12377971 BACKGROUND

• Beers SA, Chan CH, French RR, Cragg MS, Glennie MJ. CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin Hematol. 2010 Apr;47(2):107-14. doi: 10.1053/j.seminhematol.2010.01.001.

  PMID: 20350657 BACKGROUND

• Mossner E, Brunker P, Moser S, Puntener U, Schmidt C, Herter S, Grau R, Gerdes C, Nopora A, van Puijenbroek E, Ferrara C, Sondermann P, Jager C, Strein P, Fertig G, Friess T, Schull C, Bauer S, Dal Porto J, Del Nagro C, Dabbagh K, Dyer MJ, Poppema S, Klein C, Umana P. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010 Jun 3;115(22):4393-402. doi: 10.1182/blood-2009-06-225979. Epub 2010 Mar 1.

  PMID: 20194898 BACKGROUND

• Salles GA, et al. Efficacy and Safety of Obinutuzumab (GA101) Monotherapy in Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma: Results from a Phase I/II Study (BO20999) American Society of Hematology Annual meeting 2011 Abstract 268.

  BACKGROUND

• Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. doi: 10.1200/JCO.2014.59.2139. Epub 2015 Aug 17.

  PMID: 26282650 BACKGROUND

MeSH Terms

Interventions

Rituximab; obinutuzumab

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The study closed early due to slow accrual.

Results Point of Contact

• Title: PrECOG Statistician
• Organization: ECOG-ACRIN Biostatistics Center

jmanola@jimmy.harvard.edu

617-632-3627

Study Officials

• Stephen Ansell, MD

  Mayo Clinic in Minnesota

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2013
• First Posted: June 28, 2013
• Study Start: December 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: August 1, 2016
• Last Updated: May 5, 2017
• Results First Posted: May 5, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (28)