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

Phase II Pilot Study of Brentuximab Vedotin, Rituximab and Dose Attenuated CHP in Elderly Patients With DLBCL

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Prednisone; Drug: Rituximab; Drug: Brentuximab vedotin; Drug: Doxorubicin

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Institute, University of Rochester Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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of any study-specific procedure not part of routine medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Cyclophosphamide; Other Names: Cytoxan; Endoxan; Cycloblastin; Neosar; Revimmune; Lyophilizedcytoxan; Procytox; Drug: Prednisone; Other Names: Deltasone; Orasone; Adasone; Deltacortisone; Prednisonum; Drug: Rituximab; Other Names: Rituxan; Mabthera; Drug: Brentuximab vedotin; Other Names: Adcetris; SGN-35; cAC10-vcMMAE; Drug: Doxorubicin; Other Names: Caelyx; Doxil; Myocet; Adriamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects Completing Regimen	Number of subjects who complete all 6 cycles of the therapy divided by the total number of subjects.	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Number of participants who are alive after two years.	2 years
Progression Free Survival	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.	2 years
Overall Response Rate	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.	20 weeks
Complete Response Rate	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.	20 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with impairment in physical function	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.	20 weeks
mean number of falls per participant		20 weeks
Mean change in objective physical performance	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.	baseline and 20 weeks
Mean number of comorbidities		20 weeks
mean change in mini nutritional assessment	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.	baseline and 20 weeks
Number of participants with any documented change in the Older Americans Resources and Services social resources assessment.	This is a descriptive assessment.	baseline and 20 weeks
mean change in the geriatric depression screen	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.	baseline and 20 weeks
mean change in cognition score	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.	baseline and 20 weeks

Collaborators and Investigators

• Sponsor: Patrick Reagan
• Collaborators: Seagen Inc.
• Investigators: Principal Investigator: Patrick M Reagan, MD, Wilmot Cancer Institute, University of Rochester Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: April 6, 2016
• First Submitted That Met QC Criteria: April 6, 2016
• First Posted (Estimated): April 12, 2016

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: DLBCL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Immunoconjugates; Immunotoxins; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Brentuximab Vedotin
• Other Study ID Numbers: ULYM15105; IST-2014-100578 (Other Grant/Funding Number: Seattle Genetics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No