Clinical Trials /

Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma

NCT03113500

Description:

This phase II trial studies the side effects and how well brentuximab vedotin and combination chemotherapy work in treating patients with CD30-positive peripheral T-cell lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, etoposide, and prednisone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin and combination chemotherapy may work better in treating patients with CD30-positive peripheral T-cell lymphoma.

Related Conditions:
  • Adult T-Cell Leukemia/Lymphoma
  • Angioimmunoblastic T-Cell Lymphoma
  • Enteropathy-Associated T-Cell Lymphoma
  • Hepatosplenic T-Cell Lymphoma
  • Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
  • Official Title: A Phase 2 Study of Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed by BV Consolidation in Patients With CD30-Positive Peripheral T-Cell Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: 17058
  • SECONDARY ID: NCI-2017-00573
  • SECONDARY ID: 17058
  • SECONDARY ID: P30CA033572
  • NCT ID: NCT03113500

Conditions

  • Adult T-Cell Leukemia/Lymphoma
  • Anaplastic Large Cell Lymphoma, ALK-Negative
  • Anaplastic Large Cell Lymphoma, ALK-Positive
  • Angioimmunoblastic T-Cell Lymphoma
  • Ann Arbor Stage II Noncutaneous Anaplastic Large Cell Lymphoma
  • Ann Arbor Stage III Noncutaneous Anaplastic Large Cell Lymphoma
  • Ann Arbor Stage IV Noncutaneous Anaplastic Large Cell Lymphoma
  • Enteropathy-Associated T-Cell Lymphoma
  • Hepatosplenic T-Cell Lymphoma
  • Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified

Interventions

DrugSynonymsArms
Brentuximab VedotinADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35Treatment (CHEP-BV)
Cyclophosphamide(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Treatment (CHEP-BV)
DoxorubicinAdriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, HydroxyldaunorubicinTreatment (CHEP-BV)
Doxorubicin Hydrochloride5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, RubexTreatment (CHEP-BV)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16Treatment (CHEP-BV)
Etoposide PhosphateEtopophosTreatment (CHEP-BV)
Prednisone.delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-PrednisoneTreatment (CHEP-BV)

Purpose

This phase II trial studies the side effects and how well brentuximab vedotin and combination chemotherapy work in treating patients with CD30-positive peripheral T-cell lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, etoposide, and prednisone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin and combination chemotherapy may work better in treating patients with CD30-positive peripheral T-cell lymphoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Assess the safety and tolerability of cyclophosphamide, doxorubicin hydrochloride
      (doxorubicin), etoposide phosphate (etoposide), prednisone, and brentuximab vedotin
      (CHEP-BV), as induction therapy in patients with CD30-positive peripheral T-cell lymphoma
      (PTCL). (Safety lead-in) II. Assess the anti-lymphoma activity of CHEP-BV as induction
      treatment in patients with CD30-positive PTCL. (Phase 2)

      SECONDARY OBJECTIVES:

      I. Describe outcomes of CD30-positive PTCL patients who go on to receive BV consolidation
      therapy post CHEP-BV induction with/without autologous hematopoietic cell
      transplantation/radiation.

      EXPLORATORY OBJECTIVES:

      I. Explore the rate of minimal residual disease (MRD) negativity (as assessed by
      next-generation sequencing) and MRD kinetics after CHEP-BV and BV consolidation therapy in
      CD30-positive PTCL.

      II. Explore the possible association between outcome after study treatment and CD30
      expression, gene expression profiles (GEP), and genetic mutations as measured in PTCL tumor
      samples.

      OUTLINE:

      INDUCTION: Patients receive cyclophosphamide intravenously (IV) and doxorubicin IV on day 1,
      etoposide IV on days 1-3, and prednisone orally (PO) on days 1-5. Patients also receive
      brentuximab vedotin IV over approximately 30 minutes on day 1. Treatment repeats every 21
      days for up to 6 cycles (or for up to 5 cycles for patients who received 1 cycle of
      cyclophosphamide, doxorubicin, vincristine and prednisone [CHOP]-like or brentuximab vedotin,
      cyclophosphamide, doxorubicin, and prednisone [CHP-BV] therapy prior to induction, per
      investigator's discretion) in the absence of disease progression or unacceptable toxicity.

      CONSOLIDATION: Between 30-60 days post-consolidative autologous stem cell therapy,
      post-consolidative radiation therapy, or after completing induction cycle 6 (cycle 5 for
      patients who qualify for receiving 5 cycles of CHEP-BV instead of 6), patients with objective
      response (complete response or partial response) receive brentuximab vedotin IV over
      approximately 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, 6 months, and 12
      months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (CHEP-BV)ExperimentalINDUCTION: Patients receive cyclophosphamide IV and doxorubicin IV on day 1, etoposide IV on days 1-3, and prednisone PO on days 1-5. Patients also receive brentuximab vedotin IV over approximately 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (or for up to 5 cycles for patients who received 1 cycle of CHOP-like or CHP-BV therapy prior to induction, per investigator's discretion) in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Between 30-60 days post-consolidative autologous stem cell therapy, post-consolidative radiation therapy, or after completing induction cycle 6 (cycle 5 for patients who qualify for receiving 5 cycles of CHEP-BV instead of 6), patients with objective response (complete response or partial response) receive brentuximab vedotin IV over approximately 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
  • Brentuximab Vedotin
  • Cyclophosphamide
  • Doxorubicin
  • Doxorubicin Hydrochloride
  • Etoposide
  • Etoposide Phosphate
  • Prednisone

Eligibility Criteria

        Inclusion Criteria:

          -  Documented informed consent of participant and/or legally authorized representative

          -  Agreement to allow the use of archival tissue from diagnostic tumor biopsies will be
             retrieved and submitted post-enrollment

               -  If unavailable, exceptions may be granted with study principal investigator (PI)
                  approval.

          -  Eastern Cooperative Oncology Group (ECOG) status =< 2

          -  Histologically confirmed mature peripheral T-cell or natural killer (NK)-cell lymphoma
             per World Health Organization (WHO) classification, including:

               -  Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL)
                  with international protein index (IPI) of 2 or higher (must have bulky [defined
                  as mass >= 10 cm] stage II, or stage III-IV disease)

               -  ALK-negative ALCL

                    -  NOTE: Per amendment dated 05-10-19, ALCL will no longer be eligible except
                       for Canada.

               -  PTCL-not otherwise specified (NOS)

               -  Angioimmunoblastic T-cell lymphoma (AITL)

               -  Adult T-cell lymphoma/leukemia (ATLL)

               -  Enteropathy-associated T-cell lymphoma (EATL)

               -  Hepatosplenic T-cell lymphoma

          -  CD30-positivity (e.g. at least 1%) by immunohistochemistry confirmed by
             hematopathology review at the participating institution

          -  Measurable disease of at least 1.5 cm on computed tomography (CT) or positron emission
             tomography (PET)-CT scan

          -  Absolute neutrophil count (ANC) >= 1,000/mm^3

               -  Exception: unless documented bone marrow involvement by lymphoma

          -  Platelets >= 50,000/mm^3

               -  Exception: unless documented bone marrow involvement by lymphoma

          -  Total serum bilirubin =< 1.5 x upper limit of normal (ULN) OR if hepatic involvement
             by lymphoma: =< 3 x ULN for Gilbert's disease or documented hepatic involvement by
             lymphoma

          -  Aspartate aminotransferase (AST) =< 2 x ULN OR if hepatic involvement by lymphoma: AST
             =< 5 x ULN

          -  Alanine aminotransferase (ALT) =< 2 x ULN OR if hepatic involvement by lymphoma: ALT
             =< 5 x ULN

          -  Creatinine clearance of >= 60 mL/min per the Cockcroft-Gault formula

          -  Left ventricular ejection fraction (LVEF) >= 45%

          -  Women of childbearing potential (WOCBP): negative urine or serum pregnancy test; if
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required

          -  Agreement by WOCBP and males of childbearing potential to use an effective method of
             birth control or abstain from heterosexual activity for the course of the study
             through at least 6 months after the last dose of protocol therapy; childbearing
             potential defined as not being surgically sterilized (men and women) or have not been
             free from menses for > 1 year (women only)

        Exclusion Criteria:

          -  Prior treatment of PTCL with systemic anti-lymphoma therapies, investigational agents,
             radiation

               -  Exception: May have received 1 cycle of CHOP-like therapy (e.g. CHOP, CHOEP,
                  EPOCH) or 1 cycle of CHP-BV; these participants must initiate day 1 cycle 1 of
                  study therapy (CHEP-BV) no less than 19 days from prior CHOP-like or CHP-BV
                  therapy; Patients who received 1 cycle of CHOP-like or 1 cycle of CHP-BV therapy
                  prior to initiating induction with CHEP-BV are allowed to receive only 5 cycles
                  of CHEP-BV instead of 6 cycles, per investigator's discretion

          -  History of another primary invasive cancer, hematologic malignancy, or myelodysplastic
             syndrome that has not been in remission for at least 3 years.

               -  Exceptions: Non-melanoma skin cancer and in situ cervical cancer

          -  Symptomatic cardiac disease (including symptomatic ventricular dysfunction,
             symptomatic coronary artery disease, and symptomatic arrhythmias), cerebrovascular
             event/stroke or myocardial infarction within the past 6 months

          -  Central nervous system involvement by lymphoma, including leptomeningeal involvement

          -  History of progressive multifocal leukoencephalopathy (PML)

          -  Active >= grade 3 viral, bacterial, or fungal infection within 2 weeks prior to day 1
             of protocol therapy

          -  Any known human immunodeficiency virus (HIV) infection, hepatitis B surface
             antigen-positive status, or known or suspected active hepatitis C infection

          -  Baseline peripheral neuropathy >= grade 2 or patients with the demyelinating form of
             Charcot-Marie-Tooth syndrome

          -  Known severe hypersensitivity to any study related agent excipient(s)

          -  Females only: pregnant or breastfeeding

          -  Any other condition that would, in the investigator's judgement, contraindicate the
             patient's participation in the clinical study

          -  Prospective participants who, in the opinion of the investigator, may not be able to
             comply with all study procedures (including compliance issues related to
             feasibility/logistics)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete response (CR) rate after cyclophosphamide, doxorubicin, etoposide, prednisone, and brentuximab vedotin (CHEP-BV) induction therapy
Time Frame:Up to 1 year
Safety Issue:
Description:Will be estimated by the proportion of evaluable patients achieving CR after CHEP-BV induction therapy, along with the 95% exact binomial confidence interval.

Secondary Outcome Measures

Measure:Incidence of adverse events after CHEP-BV induction therapy
Time Frame:Up to 1 year
Safety Issue:
Description:Will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution. For cycle 1 only, all grade >= 2 adverse events (AEs) (highest grade or not) will also be collected.
Measure:Incidence of adverse events of brentuximab vedotin (BV) consolidation after CHEP-BV induction therapy without autologous hematopoietic stem cell transplantation (ASCT)/radiation
Time Frame:Up to 1 year
Safety Issue:
Description:Will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution. For cycle 1 only, all grade >= 2 AEs (highest grade or not) will also be collected.
Measure:Incidence of adverse events of BV consolidation after CHEP-BV induction therapy and ASCT/radiation
Time Frame:Up to 1 year
Safety Issue:
Description:Will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.
Measure:Overall response rate after induction therapy
Time Frame:Up to 1 year
Safety Issue:
Description:Will be estimated by the proportion of evaluable patients achieving overall response rate after induction therapy. Will be estimated along with the 95% exact binomial confidence interval.
Measure:CR rate after BV consolidation therapy
Time Frame:Up to 1 year
Safety Issue:
Description:Will be estimated by the proportion of evaluable patients achieving CR after BV consolidation therapy, along with the 95% exact binomial confidence interval.
Measure:Progression-free survival
Time Frame:The time from enrollment to the first observation of disease relapse/progression or death from any cause, whichever occurs first assessed up to 1 year
Safety Issue:
Description:Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.
Measure:Overall survival
Time Frame:The time from enrollment to death from any cause assessed up to 1 year
Safety Issue:
Description:Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:City of Hope Medical Center

Last Updated

February 11, 2021