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Diffuse Large B-Cell LymphomaPhase 2NCT01626352

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

A Phase 2 study testing Bendamustine and Ofatumumab in people with Diffuse Large B-Cell Lymphoma, run by SCRI Development Innovations, LLC at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 70 years and older
Conditions the study is for
Diffuse Large B-Cell Lymphoma
What is being tested?
Bendamustine and Ofatumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
11 sitesUnited States
Study dates
Oct 2012to Apr 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 70 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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
Show all 22Show fewer
  • 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:
  • Absolute neutrophil count >=1,000 cells/mm3
  • Platelet count >=75,000 cells/mm3
  • Hemoglobin >=8 g/dL
  • Creatinine <=2.0 mg/dL or Creatinine Clearance >= 40 mL/min (calculated or 24 hour urine sample)
  • AST/SGOT <=2.0 x ULN (<=5.0 x ULN if secondary to lymphoma)
  • ALT/SGPT <=2.0 x ULN (<=5.0 x ULN if secondary to lymphoma)
  • Bilirubin level of <2.0 mg/dL unless secondary to Gilbert's disease (or pattern consistent with Gilbert's)

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.
  • Male patients unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Tennessee Oncology-Chattanooga

    Chattanooga, Tennessee, 37404

  • Florida Cancer Specialists-South

    Fort Myers, Florida, 33916

  • Grand Rapids Oncology Program

    Grand Rapids, Michigan, 49503

  • Cancer Centers of Southwest Oklahoma

    Lawton, Oklahoma, 73505

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37023

  • Oklahoma University

    Oklahoma City, Oklahoma, 73104

  • Woodlands Medical Specialists

    Pensacola, Florida, 32503

  • Florida Cancer Specialists North

    St. Petersburg, Florida, 33705

  • Providence Medical Group

    Terre Haute, Indiana, 47802

  • RHHP/Hope Cancer Center

    Terre Haute, Indiana, 47802

  • Space Coast Cancer Center

    Titusville, Florida, 32796

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

While R-CHOP has improved survival and is considered standard of care for patients with DLBCL, the toxicities associated with R-CHOP are substantial in the elderly population. This is one of several reasons the outcome of older patients is worse than the corresponding younger patients. Bendamustine is an alkylating agent which causes intra- and inter-strand cross-links between DNA bases. Ofatumumab is a fully human anti-CD 20 antibody well tolerated by elderly patients. Ofatumumab targets a novel epitope of the CD20 molecule on B cells and remains on the cell surface twice as long as rituximab. The combination of both agents allows for a potentially efficacious, less toxic regimen.

Being tested
Bendamustine, Ofatumumab
Keywords
Diffuse Large B-Cell Lymphoma, Ofatumumab, Bendamustine
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BendamustineDrug

    Also called Treanda

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

  • OfatumumabDrug

    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

Study groups in NCT01626352
Study groupRoleWhat they receive
Bendamustine/OfatumumabExperimentalAll 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.
Receives: Drug: Bendamustine; Drug: Ofatumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 18 months

Secondary outcomes (6)

  1. Duration of Response

    Defined as the time from date of first documented confirmed response to date of disease progression or relapse from complete response as defined by the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). This criteria categorizes the response of a patient's tumor to treatment as Complete Response (CR): the disappearance of all disease evidence; Partial Response (PR): regression of measurable disease and no new sites; Stable Disease (SD): less than a PR but not progressive disease (PD); Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Patients who are alive and free from disease progression will be censored at the date of last tumor assessment. Patients who begin further anticancer therapy prior to disease progression will be censored at the date of last tumor assessment prior to the start date of the anticancer therapy.

    Measured: 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

  2. Time to Progression (TTP)

    Defined as the time from date of first treatment to the date of first documented disease progression or relapse from complete response as defined by the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). This criteria categorizes the response of a patient's tumor to treatment as Complete Response (CR): the disappearance of all disease evidence; Partial Response (PR): regression of measurable disease and no new sites; Stable Disease (SD): less than a PR but not progressive disease (PD); Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir.

    Measured: 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

  3. Overall Survival (OS)

    Defined as the time from Day 1 of study drug administration to date of death from any cause.

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

  4. Overall Response (OR)

    Overall response is the number of patients with observed complete or partial response (CR or PR) as assessed using the International Working Group (IMW) revised response criteria for malignant lymphoma (Cheson 2007). Complete response requires disappearance of all evidence of disease. Partial response requires regression of measurable disease and no new sites.

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

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

    A treatment-related adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events were evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

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

  6. Progression-free Survival

    Defined as the time from first treatment until objective tumor progression, relapse from complete response, or death from any cause. Tumor response is defined by the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). This criteria categorizes the response of a patient's tumor to treatment as Complete Response (CR): the disappearance of all disease evidence; Partial Response (PR): regression of measurable disease and no new sites; Stable Disease (SD): less than a PR but not progressive disease (PD); Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Patients who are alive and free from disease progression will be censored at the date of last tumor assessment.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2012 (estimated)
  2. Study startOct 2012
  3. Primary completionSep 2016
  4. Study completionApr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01626352
Sponsor's protocol ID
SCRI LYM 75
Status last verified
Oct 2017
First submitted
20 Jun 2012
Last updated
22 Nov 2017
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 16750358

  • 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.

    PubMed 17242396

  • 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.

    PubMed 1606068

  • 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.

    PubMed 6368652

  • 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.

    PubMed 14692018

  • 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.

    PubMed 21030351

  • 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.

    PubMed 11801463

  • 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.

    PubMed 11807147

  • 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.

    PubMed 24032456

  • 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.

    PubMed 3512783

  • 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.

    PubMed 15867204

  • 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.

    PubMed 16754935

  • 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.

    PubMed 20223728

  • 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.

    PubMed 18172283

  • 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.

    PubMed 8141877

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bendamustine and Ofatumumab in people with Diffuse Large B-Cell Lymphoma, run by SCRI Development Innovations, LLC at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With a Complete Response (time frame: 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01626352, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2017.

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