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A Study of Brentuximab Vedotin, Rituximab, and Dose Attenuated CHP in Elderly Patients With Diffuse Large B-Cell Lymphoma (DLBCL) (BV mini CHP)

This study is currently recruiting participants.
See Contacts and Locations
Verified March 2017 by Patrick Reagan, University of Rochester
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Patrick Reagan, University of Rochester
ClinicalTrials.gov Identifier:
NCT02734771
First received: April 6, 2016
Last updated: March 23, 2017
Last verified: March 2017
  Purpose
This is a study incorporating brentuximab vedotin and dose attenuated rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) into initial therapy for elderly patients with DLBCL. Vincristine will be omitted from the standard R-CHOP regimen given the overlapping toxicities with brentuximab vedotin.

Condition Intervention Phase
Diffuse Large B-Cell Lymphoma Drug: Brentuximab vedotin Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Prednisone Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase II Pilot Study of Brentuximab Vedotin, Rituximab and Dose Attenuated CHP in Elderly Patients With DLBCL

Resource links provided by NLM:


Further study details as provided by Patrick Reagan, University of Rochester:

Primary Outcome Measures:
  • Percent of Subjects Completing Regimen [ Time Frame: 20 weeks ]
    Number of subjects who complete all 6 cycles of the therapy divided by the total number of subjects.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 2 years ]
    Number of participants who are alive after two years.

  • Progression Free Survival [ Time Frame: 2 years ]
    Per the Lugano Criteria, progression is defined as an individual node/lesion that increases in size by 50% or in the setting of splenomegaly, the splenic length must increase by 50% of the extent of its prior increase beyond baseline (eg, a 15-cm spleen must increase to 16 cm). If no prior splenomegaly, must increase by at least 2 cm from baseline or any new or recurrent splenomegaly or new or clear progression of preexisting non-measured lesions or regrowth of previously resolved lesions. or assessable disease of any size unequivocally attributable to lymphoma or new or recurrent involvement.

  • Overall Response Rate [ Time Frame: 20 weeks ]
    The overall response rate is the proportion of subjects who achieve a complete response or partial response based on the Lugano Criteria. Per the Lugano Criteria, complete response is defined as a Deauville score of 1, 2 or 3 and partial response is defined as Deauville score of 4 or 5, but decreased from baseline. Using CT measurements a complete response is defined as decrease in lymph node size to 1.5 cm, while a partial response is a 50% or greater reduction in size in 6 target lesions.

  • Complete Response Rate [ Time Frame: 20 weeks ]
    Proportion of participants who have a complete response rate. Per the Lugano Criteria, complete response is defined as a Deauville score of 1, 2 or 3 and partial response is defined as Deauville score of 4 or 5, but decreased from baseline. Using CT measurements a complete response is defined as decrease in lymph node size to 1.5 cm, while a partial response is a 50% or greater reduction in size in 6 target lesions.


Other Outcome Measures:
  • Number of participants with impairment in physical function [ Time Frame: 20 weeks ]
    Activities of daily living (ADL): ADLs are measures of self-care. ADL independence will be assessed using the Katz Index of Independence in Activities of Daily Living, commonly referred to as the Katz ADL. The Katz ADL is the most appropriate instrument to assess functional status as a measurement of the client's ability to perform activities of daily living independently. Clinicians typically use the tool to detect problems in performing activities of daily living and to plan care accordingly. The Index ranks adequacy of performance in the six functions of bathing, dressing, toileting, transferring, continence, and feeding. Clients are scored yes/no for independence in each of the six functions. A score of 6 indicates full function, 4 indicates moderate impairment, and 2 or less indicates impairment.

  • mean number of falls per participant [ Time Frame: 20 weeks ]
  • Mean change in objective physical performance [ Time Frame: baseline and 20 weeks ]
    Physical performance will be tested using the short physical performance battery (range 0-12). Impairment is a score of less than or equal to 9.

  • Mean number of comorbidities [ Time Frame: 20 weeks ]
  • mean change in mini nutritional assessment [ Time Frame: baseline and 20 weeks ]
    The current MNA® is a 6 question assessment that identifies older adults who are malnourished or at risk of malnutrition. Scale=0-30. A score of less than or equal to 11 indicates impairment.

  • Number of participants with any documented change in the Older Americans Resources and Services social resources assessment. [ Time Frame: baseline and 20 weeks ]
    This is a descriptive assessment.

  • mean change in the geriatric depression screen [ Time Frame: baseline and 20 weeks ]
    The Geriatric Depression Scale (GDS) is a 30-item self-report assessment used to identify depression in the elderly. Scale ranges from 0-15 with a score of greater than or equal to 5 signifying impairment.

  • mean change in cognition score [ Time Frame: baseline and 20 weeks ]
    Cognition will be assessed using the blessed orientation memory-concentration (BOMC) test. The BOMC is a screening tool allowing family members, caregivers, or health care professionals to check for suspected dementia in an elderly. Dementia is described as the progressive loss of memory and at least of one other cognitive area, such as language or behavior. The scale is -20 with a score of greater than 10 signifying impairment.


Estimated Enrollment: 24
Study Start Date: June 2016
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BV+mini-R-CHP
Brentuximab vedotin 1.8 mg/kg IV day 1 for six cycles Rituximab 375 mg/m2 IV day 1 for six cycles Cyclophosphamide 400 mg/m2 IV day 1for six cycles Doxorubicin 25 mg/m2 IV day 1 for six cycles Prednisone 40 mg/m1 PO days 1-5 for six cycles
Drug: Brentuximab vedotin
Other Names:
  • Adcetris
  • SGN-35
  • cAC10-vcMMAE
Drug: Rituximab
Other Names:
  • Rituxan
  • Mabthera
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
  • Lyophilizedcytoxan
  • Endoxan
  • Neosar
  • Procytox
  • Revimmune
  • Cycloblastin
Drug: Doxorubicin
Other Names:
  • Adriamycin
  • Doxil
  • Caelyx
  • Myocet
Drug: Prednisone
Other Names:
  • Deltasone
  • Orasone
  • Adasone
  • Deltacortisone
  • Prednisonum

Detailed Description:
This is a multicenter, single-arm pilot study incorporating brentuximab vedotin and dose attenuated rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) into initial therapy for elderly patients with DLBCL. Vincristine will be omitted from the standard R-CHOP regimen given the overlapping toxicities with brentuximab vedotin. CD30 positivity will be determined at enrollment and patients will be enrolled into a CD30 positive and negative group in equal numbers. Additionally, a Comprehensive Geriatric Assessment (CGA) will be performed on all patients, but this will not be used to guide treatment decisions.
  Eligibility

Ages Eligible for Study:   75 Years and older   (Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Voluntary written informed consent before performance of any study-specific procedure not part of routine medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. Subjects must be able to understand and be willing to sign the written informed consent form.
  • Men and women aged greater than or equal to 75 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
  • Histologically-confirmed DLBCL by World Health Organization classification by site hematopathologist

    • Histologic transformation (HT) will be included on the study. This must be confirmed with a biopsy. Patients with HT must not have received an anthracycline-containing regimen in the past.
    • Composite lymphoma containing both indolent and large cell features will be included
  • Has received no prior therapy for DLBCL or HT with the exception of a course of prednisone of less than or equal to 7 days given for lymphoma related symptoms; prior therapy for follicular lymphoma is accepted, but no prior anthracycline-containing therapy.
  • Carriers of hepatitis B virus should be closely monitored for clinical and laboratory signs of active hepatitis B virus infection and for signs of hepatitis throughout study participation.
  • Total bilirubin must be less than 1.5 times the upper limit of normal (ULN) unless the elevation is known to be due to Gilbert syndrome.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be less than 3 times the upper limit of the normal range. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of DLBCL in liver.

Exclusion Criteria:

  • Patient has a platelet count of ≤50,000/mm3 within 14 days before enrollment.
  • Patient has an absolute neutrophil count of < 1,000/mm3 within 14 days before enrollment.
  • Patient has a calculated or measured creatinine clearance of <30 mL/minute within 14 days before enrollment.
  • Patient is receiving peritoneal dialysis or hemodialysis
  • Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • New York Heart Association class III heart failure or ejection fraction of less than 30% on echocardiogram or Multi Gated Acquisition Scan (MUGA)
  • Patient has received other investigational drugs with 14 days before enrollment
  • Prior exposure to anthracycline
  • Patient has concomitant active malignancy that the treating physician or PI feels may interfere with the ability to measure the primary or secondary outcomes

    • Patients with a history of curative, surgically treated basal or squamous cell carcinoma or stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible.
    • Patients with a malignancy that has been treated with surgery alone with curative intent will also be excluded, unless the malignancy has been in documented remission without treatment for ≥ 3 years prior to enrollment.
  • Patient is known to be HIV positive (test result not required for enrollment).
  • History of solid organ transplantation, or post-transplant lymphoproliferative disorder
  • Patient has history of allogeneic stem cell transplantation.
  • History of, or clinically apparent central nervous system (CNS) lymphoma
  • Any clinically significant abnormality in screening blood chemistry, hematology, or urinalysis results that, in the judgment of the investigator, would impede adequate evaluation of adverse events and/or response to treatment, or that requires aggressive intervention
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02734771

Contacts
Contact: Patrick M Reagan, MD 585-273-3258 Patrick_Reagan@urmc.rochester.edu
Contact: Yelena Lerman, PhD 585-276-8333 YLerman@urmc.rochester.edu

Locations
United States, New York
James P. Wilmot Cancer Institute, University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Patrick M Reagan, MD    585-273-3258    Patrick_Reagan@urmc.rochester.edu   
Contact: Yelena Lerman, PhD    585-275-8333    YLerman@urmc.rochester.edu   
United States, Virginia
University of Virginia Cancer Center Not yet recruiting
Charlottesville, Virginia, United States, 22908
Contact: Kathleen Bohorfoush, RN, MSN    434-243-6152    KEC@virginia.edu   
Sponsors and Collaborators
Patrick Reagan
Seattle Genetics, Inc.
Investigators
Principal Investigator: Patrick M Reagan, MD Wilmot Cancer Institute, University of Rochester Medical Center
  More Information

Responsible Party: Patrick Reagan, Senior Instructor, Hematology/Oncology, University of Rochester
ClinicalTrials.gov Identifier: NCT02734771     History of Changes
Other Study ID Numbers: ULYM15105
IST-2014-100578 ( Other Grant/Funding Number: Seattle Genetics )
Study First Received: April 6, 2016
Last Updated: March 23, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Patrick Reagan, University of Rochester:
DLBCL

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Doxorubicin
Prednisone
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on June 28, 2017