Study of Bendamustine and Ofatumumab in Elderly Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy

NCT01626352 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SCRI LYM 75
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 11

Brief Summary

This is a single-arm, Phase II study designed to enroll and treat up to 64 patients. All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Patients will receive as an IV infusion bendamustine Days 1 and 2 of Cycles 1 through 6 and ofatumumab Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6.

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

Diffuse Large B-Cell Lymphoma; Ofatumumab; Bendamustine

Outcome Measures

Primary Outcomes (1)

• Number of Patients With a Complete Response

  Disease response assessments will be performed using the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). Complete response requires a disappearance of all evidence of disease.

  18 months

Secondary Outcomes (6)

• Duration of Response

  After cycles 3 and 6 of each 21-day cycle and every 3 months thereafter until disease progression or relapse from complete response for up to 38 months

• Time to Progression (TTP)

  After cycles 3 and 6 of each 21-day cycle, and every 3 months thereafter until progression or relapse from complete response for up to 40 months

• Overall Survival (OS)

  every 3 cycles during treatment and every 3 months thereafter until progression or death from any cause, projected 18 months

• Overall Response (OR)

  after cycles 3 and 6 of each 21-day cycle, and every 3 months thereafter, projected 18 months

• Number of Patients With Treatment-Related Adverse Events (AEs) as a Measure of Safety

  after cycles 3 and 6 of each 21-day cycle, and up to 30 days after last dose, projected 24 weeks

Study Arms (1)

Bendamustine/Ofatumumab

EXPERIMENTAL

All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Patients will receive as an IV infusion of bendamustine Days 1 and 2 of Cycles 1-6, ofatumumab Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2-6.

Drug: Bendamustine; Drug: Ofatumumab

Interventions

Bendamustine DRUG

Patients will receive as an IV infusion bendamustine 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6.

Also known as: Treanda

Bendamustine/Ofatumumab

Ofatumumab DRUG

Patients will receive as an IV infusion ofatumumab 1000-mg IV Days 1 and 8 during Cycle 1 only, and on Day 1 of Cycles 2 through 6

Bendamustine/Ofatumumab

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Histologically confirmed CD20-positive DLBCL.
• Newly diagnosed, stage III-IV DLBCL considered poor candidates for R-CHOP.
• Age \>=70 years
• At least one of the following criteria:
• ECOG PS 2
• Cardiac compromise precluding anthracycline therapy
• Previous anthracycline therapy for other malignancy precluding further anthracycline therapy.
• Severe coexisting medical problems
• General frailty
• ECOG 0-2
• Measurable disease with at least one bidimensional lymph node or tumor mass \>1.5 cm in the longest diameter that can be followed for response as a target lesion as measured by CT
• Patients must be HBV sAg and HBV cAb negative within 6 weeks of screening.
• Patient must understand and voluntarily sign the IRB-approved informed consent.
• Life expectancy \>= 3 months
• Laboratory parameters:

You may not qualify if:

• Patients with active/symptomatic central nervous system (CNS) involvement based on clinical evaluation by lumbar puncture, PET, CT or MRI.
• Known sensitivity to bendamustine or any component of bendamustine.
• Known anaphylaxis or sensitivity to ofatumumab.
• Major surgery within 28 days of Cycle 1, Day 1. Patients undergoing minor surgery within 7 days of Cycle 1, Day 1. (no wait needed for port placement)
• Prior chemotherapy, immunotherapy, or irradiation for lymphoma.
• Prior use of investigational anti-cancer agents for lymphoma.
• HIV-related lymphoma.
• Known active HIV or HCV infection, or known seropositivity for HIV, or current or chronic HBV or HCV infection. HBV test required at screening or a negative result within 6 weeks of screening.
• Concurrent active or history of other malignancies, except non-melanoma skin cancer or carcinoma in situ of cervix or breast. Patients with previous malignancies are eligible provided they have been treated with curative intent and disease free for \>= 1 year.
• Serious (grade 3-4), active, intercurrent infection requiring therapy, or deep seated or systemic mycotic infections.
• Myocardial infarction within 6 months prior to registration or New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities, in the judgment of the Investigator.
• Concurrent uncontrolled serious medical or psychiatric conditions likely to interfere with participation in this clinical study, in the judgment of the Investigator
• Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
• Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study.
• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator
• GlaxoSmithKline: collaborator
• Cephalon: collaborator

Study Sites (11)

Florida Cancer Specialists-South

Fort Myers, Florida, 33916, United States

Location

Woodlands Medical Specialists

Pensacola, Florida, 32503, United States

Location

Florida Cancer Specialists North

St. Petersburg, Florida, 33705, United States

Location

Space Coast Cancer Center

Titusville, Florida, 32796, United States

Location

Providence Medical Group

Terre Haute, Indiana, 47802, United States

Location

RHHP/Hope Cancer Center

Terre Haute, Indiana, 47802, United States

Location

Grand Rapids Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

Cancer Centers of Southwest Oklahoma

Lawton, Oklahoma, 73505, United States

Location

Oklahoma University

Oklahoma City, Oklahoma, 73104, United States

Location

Tennessee Oncology-Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Related Publications (23)

• Aapro MS, Cameron DA, Pettengell R, Bohlius J, Crawford J, Ellis M, Kearney N, Lyman GH, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C; European Organisation for Research and Treatment of Cancer (EORTC) Granulocyte Colony-Stimulating Factor (G-CSF) Guidelines Working Party. EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur J Cancer. 2006 Oct;42(15):2433-53. doi: 10.1016/j.ejca.2006.05.002. Epub 2006 Jun 5.

  PMID: 16750358 BACKGROUND

• Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.

  PMID: 17242396 BACKGROUND

• Ansell SM, Falkson G, van der Merwe R, Uys A. Chronological age is a multifactorial prognostic variable in patients with non-Hodgkin's lymphoma. Ann Oncol. 1992 Jan;3(1):45-50. doi: 10.1093/oxfordjournals.annonc.a058068.

  PMID: 1606068 BACKGROUND

• Armitage JO, Potter JF. Aggressive chemotherapy for diffuse histiocytic lymphoma in the elderly: increased complications with advancing age. J Am Geriatr Soc. 1984 Apr;32(4):269-73. doi: 10.1111/j.1532-5415.1984.tb02020.x.

  PMID: 6368652 BACKGROUND

• Balducci L, Repetto L. Increased risk of myelotoxicity in elderly patients with non-Hodgkin lymphoma. Cancer. 2004 Jan 1;100(1):6-11. doi: 10.1002/cncr.11861. No abstract available.

  PMID: 14692018 BACKGROUND

• Chang JE, Seo S, Kim KM, Werndli JE, Bottner WA, Rodrigues GA, Sanchez FA, Saphner TJ, Longo WL, Kahl BS. Rituximab and CHOP chemotherapy plus GM-CSF for previously untreated diffuse large B-cell lymphoma in the elderly: a Wisconsin oncology network study. Clin Lymphoma Myeloma Leuk. 2010 Oct;10(5):379-84. doi: 10.3816/CLML.2010.n.071.

  PMID: 21030351 BACKGROUND

• Chow KU, Sommerlad WD, Boehrer S, Schneider B, Seipelt G, Rummel MJ, Hoelzer D, Mitrou PS, Weidmann E. Anti-CD20 antibody (IDEC-C2B8, rituximab) enhances efficacy of cytotoxic drugs on neoplastic lymphocytes in vitro: role of cytokines, complement, and caspases. Haematologica. 2002 Jan;87(1):33-43.

  PMID: 11801463 BACKGROUND

• Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795.

  PMID: 11807147 BACKGROUND

• Coiffier B, Radford J, Bosly A, Martinelli G, Verhoef G, Barca G, Davies A, Decaudin D, Gallop-Evans E, Padmanabhan-Iyer S, Van Eygen K, Wu KL, Gupta IV, Lin TS, Goldstein N, Jewell RC, Winter P, Lisby S; 415 study investigators. A multicentre, phase II trial of ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Haematol. 2013 Nov;163(3):334-42. doi: 10.1111/bjh.12537. Epub 2013 Aug 23.

  PMID: 24032456 BACKGROUND

• Dixon DO, Neilan B, Jones SE, Lipschitz DA, Miller TP, Grozea PN, Wilson HE. Effect of age on therapeutic outcome in advanced diffuse histiocytic lymphoma: the Southwest Oncology Group experience. J Clin Oncol. 1986 Mar;4(3):295-305. doi: 10.1200/JCO.1986.4.3.295.

  PMID: 3512783 BACKGROUND

• Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. doi: 10.1200/JCO.2005.09.131. Epub 2005 May 2.

  PMID: 15867204 BACKGROUND

• Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. doi: 10.1200/JCO.2005.05.1003. Epub 2006 Jun 5.

  PMID: 16754935 BACKGROUND

• Hainsworth JD, Flinn IW, Spigel DR, Clark BL, Griner PL, Vazquez ER, Doss HH, Shipley D, Franco LA, Burris HA 3rd, Greco FA; Sarah Cannon Oncology Research Consortium. Brief-duration rituximab/chemotherapy followed by maintenance rituximab in patients with diffuse large B-cell lymphoma who are poor candidates for R-CHOP chemotherapy: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma Leuk. 2010 Feb;10(1):44-50. doi: 10.3816/CLML.2010.n.004.

  PMID: 20223728 BACKGROUND

• Leoni LM, Bailey B, Reifert J, Bendall HH, Zeller RW, Corbeil J, Elliott G, Niemeyer CC. Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res. 2008 Jan 1;14(1):309-17. doi: 10.1158/1078-0432.CCR-07-1061.

  PMID: 18172283 BACKGROUND

• International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993 Sep 30;329(14):987-94. doi: 10.1056/NEJM199309303291402.

  PMID: 8141877 BACKGROUND

• Lipschitz DA. Age-related declines in hematopoietic reserve capacity. Semin Oncol. 1995 Feb;22(1 Suppl 1):3-5. No abstract available.

  PMID: 7863350 BACKGROUND

• Ozer H, Armitage JO, Bennett CL, Crawford J, Demetri GD, Pizzo PA, Schiffer CA, Smith TJ, Somlo G, Wade JC, Wade JL 3rd, Winn RJ, Wozniak AJ, Somerfield MR; American Society of Clinical Oncology. 2000 update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. American Society of Clinical Oncology Growth Factors Expert Panel. J Clin Oncol. 2000 Oct 15;18(20):3558-85. doi: 10.1200/JCO.2000.18.20.3558. No abstract available.

  PMID: 11032599 BACKGROUND

• Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trumper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. doi: 10.1016/S1470-2045(08)70002-0. Epub 2008 Jan 15.

  PMID: 18226581 BACKGROUND

• Strumberg D, Harstrick A, Doll K, Hoffmann B, Seeber S. Bendamustine hydrochloride activity against doxorubicin-resistant human breast carcinoma cell lines. Anticancer Drugs. 1996 Jun;7(4):415-21. doi: 10.1097/00001813-199606000-00007.

  PMID: 8826610 BACKGROUND

• van Spronsen DJ, Janssen-Heijnen ML, Breed WP, Coebergh JW. Prevalence of co-morbidity and its relationship to treatment among unselected patients with Hodgkin's disease and non-Hodgkin's lymphoma, 1993-1996. Ann Hematol. 1999 Jul;78(7):315-9. doi: 10.1007/s002770050521.

  PMID: 10466443 BACKGROUND

• Weidmann E, Kim SZ, Rost A, Schuppert H, Seipelt G, Hoelzer D, Mitrou PS. Bendamustine is effective in relapsed or refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2002 Aug;13(8):1285-9. doi: 10.1093/annonc/mdf189.

  PMID: 12181253 BACKGROUND

• Weidmann E, Neumann A, Fauth F, Atmaca A, Al-Batran SE, Pauligk C, Jager E. Phase II study of bendamustine in combination with rituximab as first-line treatment in patients 80 years or older with aggressive B-cell lymphomas. Ann Oncol. 2011 Aug;22(8):1839-44. doi: 10.1093/annonc/mdq671. Epub 2011 Jan 21.

  PMID: 21257672 BACKGROUND

• Flinn IW, Erter J, Daniel DB, Mace JR, Berdeja JG. Phase II Study of Bendamustine and Ofatumumab in Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy. Oncologist. 2019 Aug;24(8):1035-e623. doi: 10.1634/theoncologist.2019-0286. Epub 2019 May 9.

  PMID: 31073022 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Bendamustine Hydrochloride; ofatumumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Charles H. Davis
• Organization: Sarah Cannon Research Institute

charles.davis2@scri-innovations.com

615-524-4341

Study Officials

• Ian Flinn, MD, PhD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 20, 2012
• First Posted: June 22, 2012
• Study Start: October 1, 2012
• Primary Completion: September 1, 2016
• Study Completion: April 1, 2017
• Last Updated: November 22, 2017
• Results First Posted: October 18, 2017

Record last verified: 2017-10

Locations

US (11)