Monoclonal Antibody Therapy and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

• ClinicalTrials.gov Identifier: NCT00301821
• Recruitment Status: Completed
• First Posted: March 13, 2006
• Results First Posted: March 24, 2015
• Last Update Posted: October 9, 2019
• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Alliance for Clinical Trials in Oncology

Tracking Information

• First Submitted Date: March 9, 2006
• First Posted Date: March 13, 2006
• Results First Submitted Date: March 13, 2015
• Results First Posted Date: March 24, 2015
• Last Update Posted Date: October 9, 2019
• Study Start Date: January 2006
• Actual Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 7, 2015)

Event-free Survival After 12 Months [ Time Frame: From Baseline to 12 months ]

The primary endpoint of the trial was the percentage of the eligible patients who were alive and event-free 12 months after enrollment to the study (EFS12).

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: March 31, 2015)

• Overall Survival [ Time Frame: time from study entry to 36 months ]
  Percentage of participants alive at different time points
• Progression-free Survival (PFS) [ Time Frame: the time from study entry to 36 months ]
  Percentage of participants Progression-free at different time points. Response was assessed using International Workshop Response Criteria.38 Response is based on CT alone. Relapse or progression is defined as Enlarging liver/spleen, new sites, New or increased lymph nodes, New or Increased lymph node masses, bone marrow reappearance.
• Overall Response Rate (ORR) [ Time Frame: Baseline to first 6 cycles of treatment ]
  Overall response rate will be estimated by the number of patients with objective status of partial response (PR), unconfirmed complete response (CRu), or complete response (CR) during the first 6 cycles of treatment divided by number of evaluable patients (met eligibility criteria, signed consent form, and started treatment). Response was assessed using International Workshop Response Criteria.38 Response is based on CT alone. Relapse or progression is defined as Enlarging liver/spleen, new sites, New or increased lymph nodes, New or Increased lymph node masses, bone marrow reappearance.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Monoclonal Antibody Therapy and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma
• Official Title: A Phase II Study of Epratuzumab, Rituximab (ER)-CHOP for Patients With Previously Untreated Diffuse Large B-Cell Lymphoma
• Brief Summary: RATIONALE: Monoclonal antibodies, such as epratuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody therapy together with chemotherapy may kill more cancer cells.> PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell lymphoma.

Detailed Description

OBJECTIVES:> Primary>

• Assess the efficacy of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP), as measured by 12-month, event-free survival, in patients with previously untreated stage II, III, or IV diffuse large B-cell lymphoma.>
• Assess the use of positron emission tomography (PET) scan routinely early in treatment and after completion of treatment.>
• Assess the functional response rate (complete response, partial response, or stable disease by CT scan and PET negative) in patients treated with this regimen.>
• Assess the safety of this treatment regimen.> Secondary>
• Correlate laboratory prognostic factors for large cell lymphoma with clinical response to this regimen.> OUTLINE: This is a multicenter study.> Patients receive epratuzumab IV over 1 hour on day 1, rituximab IV over 4-8 hours on day 1 or days 1 and 2, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 or 2, and oral prednisone on days 1-5 or 2-6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.> After completion of study treatment, patients are followed periodically for up to 5 years.> PROJECTED ACCRUAL: A total of 86 patients will be accrued for this study.>

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma

Intervention

• Biological: epratuzumab
• Biological: rituximab
• Drug: cyclophosphamide
• Drug: doxorubicin hydrochloride
• Drug: prednisone
• Drug: vincristine sulfate

Study Arms

Experimental: Epratuzumab + Rituximab + CHOP

One arm open label.

Interventions:

• Biological: epratuzumab
• Biological: rituximab
• Drug: cyclophosphamide
• Drug: doxorubicin hydrochloride
• Drug: prednisone
• Drug: vincristine sulfate

Publications *

• Micallef IN, Kahl BS, Maurer MJ, Dogan A, Ansell SM, Colgan JP, Geyer S, Inwards DJ, White WL, Habermann TM. A pilot study of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated, diffuse large B-cell lymphoma. Cancer. 2006 Dec 15;107(12):2826-32. doi: 10.1002/cncr.22342.
• Maurer MJ, Micallef IN, Cerhan JR, Katzmann JA, Link BK, Colgan JP, Habermann TM, Inwards DJ, Markovic SN, Ansell SM, Porrata LF, Johnston PB, Nowakowski GS, Thompson CA, Gupta M, Syrbu SI, Kurtin PJ, Macon WR, Nikcevich DA, Witzig TE. Elevated serum free light chains are associated with event-free and overall survival in two independent cohorts of patients with diffuse large B-cell lymphoma. J Clin Oncol. 2011 Apr 20;29(12):1620-6. doi: 10.1200/JCO.2010.29.4413. Epub 2011 Mar 7.
• Micallef IN, Maurer MJ, Wiseman GA, Nikcevich DA, Kurtin PJ, Cannon MW, Perez DG, Soori GS, Link BK, Habermann TM, Witzig TE. Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma. Blood. 2011 Oct 13;118(15):4053-61. doi: 10.1182/blood-2011-02-336990. Epub 2011 Jun 14.
• Micallef IN, Maurer MJ, Nikcevich DA, et al.: Final results of NCCTG N0489: epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (ER-CHOP) in patients with previously untreated diffuse large B-cell lymphoma. [Abstract] J Clin Oncol 27 (Suppl 15): A-8508, 2009.
• Ghesquieres H, Larrabee BR, Haioun C, Link BK, Verney A, Slager SL, Ketterer N, Ansell SM, Delarue R, Maurer MJ, Fitoussi O, Habermann TM, Peyrade F, Dogan A, Molina TJ, Novak AJ, Tilly H, Cerhan JR, Salles G. FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts. Hematol Oncol. 2017 Dec;35(4):447-455. doi: 10.1002/hon.2305. Epub 2016 Jun 10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 13, 2015): 107
• Original Enrollment: Not Provided
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell lymphoma

  • B-cell phenotype (CD20+) as determined by immunohistochemistry (IHC) or flow cytometry
  • Stage II, III, or IV disease
• CD22+ tumor by IHC*

NOTE: *CD22 status may be determined after study enrollment

• Measurable disease, defined as at least 1 lesion ≥ 1.5 cm by CT scan or physical exam
• No relapsed or refractory non-Hodgkin's lymphoma
• No history of transformed lymphoma

• No CNS lymphoma

  • CNS symptoms or bone marrow or sinus involvement must have absence of CNS lymphoma confirmed by lumbar puncture

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-3

  - For patients with ECOG PS 3, the PS must be disease related

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ 2 mg/dL (if total bilirubin > 2 mg/dL, direct bilirubin should be within normal limits)
• AST ≤ 3 times upper limit of normal (ULN) (5 times ULN if there is liver involvement)
• Creatinine ≤ 2 times ULN
• Life expectancy ≥ 12 weeks
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after completion of study treatment
• No active serious infection requiring antibiotics
• No New York Heart Association class III or IV heart disease
• No other primary malignancy within the past 5 years, except for squamous cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or previously treated prostate cancer with a stable prostate-specific antigen
• No known HIV positivity
• No known hepatitis B or C infection
• Ejection fraction ≥ 45% by MUGA or echocardiogram (required if patients has a history of heart disease or is ≥ 50 years old)
• Willing to provide blood and tissue samples for mandatory translational research component of study

PRIOR CONCURRENT THERAPY:

• No prior therapy for diffuse large B-cell lymphoma, including the following:

  • Chemotherapy
  • Immunotherapy
  • Biologic therapy
  • Radiotherapy
• Prior short course (≤ 14 days) of corticosteroids allowed
• Prior splenectomy allowed
• No prior pelvic irradiation
• No other concurrent investigational agents
• No concurrent chemotherapy, immunotherapy, or radiotherapy
• No concurrent enrollment on another treatment study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00301821
• Other Study ID Numbers: NCCTG-N0489; NCI-2012-02685 ( Registry Identifier: CTRP (Clinical Trials Reporting System) ); CDR0000459932 ( Registry Identifier: PDQ (Physician Data Query) )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Alliance for Clinical Trials in Oncology
• Original Responsible Party: Not Provided
• Current Study Sponsor: Alliance for Clinical Trials in Oncology
• Original Study Sponsor: North Central Cancer Treatment Group
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Ivana Micallef, MD; Mayo Clinic

• PRS Account: Alliance for Clinical Trials in Oncology
• Verification Date: October 2019