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. Monoclonal antibodies, such as brentuximab vedotin may interfere with the ability of cancer cells to grow and spread. 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
  • Anaplastic Large Cell 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, NOS
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
  • 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
  • CD30-Positive Neoplastic Cells Present
  • 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
  • Stage III Anaplastic Large Cell Lymphoma
  • Stage IV Anaplastic Large Cell Lymphoma

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, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Treatment (CHEP-BV)
DoxorubicinAdriablastin, Hydroxyl Daunorubicin, HydroxydaunorubicinTreatment (CHEP-BV)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213Treatment (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, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, 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. Monoclonal antibodies, such as brentuximab vedotin may interfere with the ability of cancer cells to grow and spread. 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, 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.

      TERTIARY 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 30 minutes on day 1. Treatment repeats every 21 days for up to 6
      courses in the absence of disease progression or unacceptable toxicity.

      CONSOLIDATION: Between 30-60 days post-consolidative autologous stem cell therapy or after
      completing induction course 6, patients with objective response (compete response or partial
      response) receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21
      days for up to 10 courses 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, 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 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Between 30-60 days post-consolidative autologous stem cell therapy or after completing induction course 6, patients with objective response (compete response or partial response) receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.
  • Brentuximab Vedotin
  • Cyclophosphamide
  • Doxorubicin
  • Etoposide
  • 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 >= 10cm] stage II, or stage III-IV disease)

               -  ALK-negative ALCL

               -  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:

          -  Brentuximab vedotin

          -  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); these participants must initiate day 1 cycle 1 of CHEP-BV no less than
             19 days from prior CHOP-like therapy; Patients who received 1 cycle of CHOP‐like
             therapy prior to initiating induction with CHEP‐BV will receive a total of 7 cycles (1
             CHOP‐like cycle prior to study therapy + 6 cycles of study therapy)

          -  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 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 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: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: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 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:Incidence of adverse events of BV consolidation after CHEP-BV induction therapy without 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: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: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.
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.

Details

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

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