Adult T-Cell Leukemia/LymphomaPhase 2NCT03113500
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
A Phase 2 study testing Brentuximab Vedotin, Cyclophosphamide and Doxorubicin in people with Adult T-Cell Leukemia/Lymphoma and Anaplastic Large Cell Lymphoma, ALK-Negative, run by City of Hope Medical Center at 5 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative, Anaplastic Large Cell Lymphoma, ALK-Positive
- What is being tested?
- Brentuximab Vedotin, Cyclophosphamide and Doxorubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 25 May 2017to 25 Apr 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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)
Who cannot join
- 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
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- 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)
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Hackensack University Medical Center
Hackensack, New Jersey, 07601
M D Anderson Cancer Center
Houston, Texas, 77030
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- 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
- Being tested
- Brentuximab Vedotin, Cyclophosphamide, Doxorubicin, Doxorubicin Hydrochloride, Etoposide
- Medical subject headings
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Enteropathy-Associated T-Cell Lymphoma, Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brentuximab VedotinDrug
Also called ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
DoxorubicinDrug
Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Given IV
Also called 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
Given IV
EtoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar
Given IV
Etoposide PhosphateDrug
Also called Etopophos
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
PrednisoneDrug
Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (CHEP-BV) | Experimental | 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. Receives: Drug: Brentuximab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Drug: Etoposide Phosphate; Other: Laboratory Biomarker Analysis; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to the end of the CHEP-BV treatment
Secondary outcomes (1)
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.
Measured: The time from enrollment to death from any cause assessed up to 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2017
- Study start25 May 2017
- Primary completion16 Jul 2021
- Study completion25 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult T-Cell Leukemia/LymphomaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Alex F Herrera, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03113500
- Sponsor's protocol ID
- 17058
- Other IDs
- NCI-2017-00573, 17058, P30CA033572
- Status last verified
- Aug 2026
- First submitted
- 10 Apr 2017
- Last updated
- 21 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Herrera AF, Zain J, Savage KJ, Feldman T, Brammer JE, Chen L, Puverel S, Popplewell L, Budde LE, Mei M, Hosing C, Nair R, Leslie L, Daniels S, Peters L, Forman S, Rosen S, Kwak L, Iyer SP. Brentuximab vedotin plus cyclophosphamide, doxorubicin, etoposide, and prednisone followed by brentuximab vedotin consolidation in CD30-positive peripheral T-cell lymphomas: a multicentre, single-arm, phase 2 study. Lancet Haematol. 2024 Sep;11(9):e671-e681. doi: 10.1016/S2352-3026(24)00171-6. Epub 2024 Jul 24.
PubMed 39067464