Clinical Trials /

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

NCT02734771

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.

Related Conditions:
  • B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
Brentuximab vedotinAdcetris, SGN-35, cAC10-vcMMAEBV+mini-R-CHP
RituximabRituxan, MabtheraBV+mini-R-CHP
CyclophosphamideCytoxan, Lyophilizedcytoxan, Endoxan, Neosar, Procytox, Revimmune, CycloblastinBV+mini-R-CHP
DoxorubicinAdriamycin, Doxil, Caelyx, MyocetBV+mini-R-CHP
PrednisoneDeltasone, Orasone, Adasone, Deltacortisone, PrednisonumBV+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

NameTypeDescriptionInterventions
BV+mini-R-CHPExperimentalBrentuximab 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:Recruiting
Lead Sponsor:Patrick Reagan

Trial Keywords

  • DLBCL

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