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

Primary Purpose

Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative, Anaplastic Large Cell Lymphoma, ALK-Positive

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Brentuximab Vedotin
Cyclophosphamide
Doxorubicin
Doxorubicin Hydrochloride
Etoposide
Etoposide Phosphate
Laboratory Biomarker Analysis
Prednisone
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult T-Cell Leukemia/Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • City of Hope Comprehensive Cancer Center
  • Hackensack University Medical Center
  • Ohio State University Comprehensive Cancer Center
  • M D Anderson Cancer Center
  • BCCA-Vancouver Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (CHEP-BV)

Arm Description

INDUCTION: 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.

Outcomes

Primary Outcome Measures

Complete Response (CR) Rate After Cyclophosphamide, Doxorubicin, Etoposide, Prednisone, and Brentuximab Vedotin (CHEP-BV) Induction Therapy
CR rate was 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

Overall Survival at 1 Year
Overall survival (OS) was measured from enrollment to death from any cause. OS was estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.

Full Information

First Posted
April 10, 2017
Last Updated
June 19, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03113500
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 25, 2017 (Actual)
Primary Completion Date
July 16, 2021 (Actual)
Study Completion Date
December 21, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (CHEP-BV)
Arm Type
Experimental
Arm Description
INDUCTION: 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.
Intervention Type
Drug
Intervention Name(s)
Brentuximab Vedotin
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-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- 138719
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Doxorubicin Hydrochloride
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Etoposide Phosphate
Other Intervention Name(s)
Etopophos
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
.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
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Complete Response (CR) Rate After Cyclophosphamide, Doxorubicin, Etoposide, Prednisone, and Brentuximab Vedotin (CHEP-BV) Induction Therapy
Description
CR rate was estimated by the proportion of evaluable patients achieving CR after CHEP-BV induction therapy, along with the 95% exact binomial confidence interval.
Time Frame
Up to the end of the CHEP-BV treatment
Secondary Outcome Measure Information:
Title
Overall Survival at 1 Year
Description
Overall survival (OS) was measured from enrollment to death from any cause. OS was estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.
Time Frame
The time from enrollment to death from any cause assessed up to 1 year.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alex F Herrera
Organizational Affiliation
City of Hope Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
BCCA-Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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