Description:
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.
Title
- Brief Title: A Study of Brentuximab Vedotin, Rituximab, and Dose Attenuated CHP in Elderly Patients With Diffuse Large B-Cell Lymphoma (DLBCL)
- Official Title: Phase II Pilot Study of Brentuximab Vedotin, Rituximab and Dose Attenuated CHP in Elderly Patients With DLBCL
Clinical Trial IDs
- ORG STUDY ID:
ULYM15105
- SECONDARY ID:
IST-2014-100578
- NCT ID:
NCT02734771
Conditions
- Diffuse Large B-Cell Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
Brentuximab vedotin | Adcetris, SGN-35, cAC10-vcMMAE | BV+mini-R-CHP |
Rituximab | Rituxan, Mabthera | BV+mini-R-CHP |
Cyclophosphamide | Cytoxan, Lyophilizedcytoxan, Endoxan, Neosar, Procytox, Revimmune, Cycloblastin | BV+mini-R-CHP |
Doxorubicin | Adriamycin, Doxil, Caelyx, Myocet | BV+mini-R-CHP |
Prednisone | Deltasone, Orasone, Adasone, Deltacortisone, Prednisonum | BV+mini-R-CHP |
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
BV+mini-R-CHP | Experimental | 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 | - Brentuximab vedotin
- Rituximab
- Cyclophosphamide
- Doxorubicin
- Prednisone
|
Eligibility 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 75 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Percent of Subjects Completing Regimen |
Time Frame: | 20 weeks |
Safety Issue: | |
Description: | Number of subjects who complete all 6 cycles of the therapy divided by the total number of subjects. |
Secondary Outcome Measures
Measure: | Overall Survival |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Number of participants who are alive after two years. |
Measure: | Progression Free Survival |
Time Frame: | 2 years |
Safety Issue: | |
Description: | 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. |
Measure: | Overall Response Rate |
Time Frame: | 20 weeks |
Safety Issue: | |
Description: | 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. |
Measure: | Complete Response Rate |
Time Frame: | 20 weeks |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Patrick Reagan |
Trial Keywords
Last Updated
September 17, 2020