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

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ClinicalTrials.gov Identifier: NCT03113500
Recruitment Status : Recruiting
First Posted : April 13, 2017
Last Update Posted : July 26, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 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 Drug: Brentuximab Vedotin Drug: Cyclophosphamide Drug: Doxorubicin Drug: Doxorubicin Hydrochloride Drug: Etoposide Other: Laboratory Biomarker Analysis Drug: Prednisone Phase 2

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.

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 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles 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, 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 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 25, 2017
Estimated Primary Completion Date : January 21, 2020
Estimated Study Completion Date : January 21, 2020


Arm Intervention/treatment
Experimental: Treatment (CHEP-BV)

INDUCTION: 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 cycles 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, 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 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Brentuximab Vedotin
Given IV
Other Names:
  • ADC 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-35

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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- 138719

Drug: Doxorubicin
Given IV
Other Names:
  • Adriablastin
  • Hydroxydaunomycin
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 5,12-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
  • Rubex

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Prednisone
Given PO
Other Names:
  • .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-Prednisone




Primary Outcome Measures :
  1. Complete response (CR) rate after cyclophosphamide, doxorubicin, etoposide, prednisone, and brentuximab vedotin (CHEP-BV) induction therapy [ Time Frame: Up to 1 year ]
    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 :
  1. Incidence of adverse events after CHEP-BV induction therapy [ Time Frame: Up to 1 year ]
    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.

  2. 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 ]
    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.

  3. Incidence of adverse events of BV consolidation after CHEP-BV induction therapy and ASCT/radiation [ Time Frame: Up to 1 year ]
    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.

  4. Overall response rate after induction therapy [ Time Frame: Up to 1 year ]
    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.

  5. CR rate after BV consolidation therapy [ Time Frame: Up to 1 year ]
    Will be estimated by the proportion of evaluable patients achieving CR after BV consolidation therapy, along with the 95% exact binomial confidence interval.

  6. 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 ]
    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.

  7. Overall survival [ Time Frame: The time from enrollment to death from any cause assessed up to 1 year ]
    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

      • 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:

  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03113500


Locations
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United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Alex F. Herrera    626-256-4673 ext 62405    aherrera@coh.org   
Principal Investigator: Alex F. Herrera         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Tatyana A. Feldman    551-996-4469    Tatyana.Feldman@hackensackmeridian.org   
Principal Investigator: Tatyana A. Feldman         
United States, Ohio
Ohio State University Comprehensive Cancer Center Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: Jonathan E. Brammer    614-366-6963    Jonathan.Brammer@osumc.edu   
Principal Investigator: Jonathan E. Brammer         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Swaminathan P. Iyer    713-792-5242    spiyer@mdanderson.org   
Principal Investigator: Swaminathan P. Iyer         
Canada, British Columbia
BCCA-Vancouver Cancer Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Kerry J. Savage       KSavage@bccancer.bc.ca   
Principal Investigator: Kerry J. Savage         
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Alex F Herrera City of Hope Medical Center

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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT03113500     History of Changes
Other Study ID Numbers: 17058
NCI-2017-00573 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17058 ( Other Identifier: City of Hope Medical Center )
First Posted: April 13, 2017    Key Record Dates
Last Update Posted: July 26, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Enteropathy-Associated T-Cell Lymphoma
Immunoblastic Lymphadenopathy
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Leukemia
Lymphadenopathy
Prednisone
Cortisone
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Etoposide
Etoposide phosphate
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunosuppressive Agents