Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
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| ClinicalTrials.gov Identifier: NCT03113500 |
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Recruitment Status :
Recruiting
First Posted : April 13, 2017
Last Update Posted : July 13, 2020
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| 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 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 Drug: Etoposide Phosphate Other: Laboratory Biomarker Analysis Drug: Prednisone | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 53 participants |
| Allocation: | N/A |
| 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, 2021 |
| Estimated Study Completion Date : | January 21, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (CHEP-BV)
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. |
Drug: Brentuximab Vedotin
Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Doxorubicin Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos Other: Laboratory Biomarker Analysis Correlative studies Drug: Prednisone Given PO
Other Names:
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- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Documented informed consent of participant and/or legally authorized representative
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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
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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
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Absolute neutrophil count (ANC) >= 1,000/mm^3
- Exception: unless documented bone marrow involvement by lymphoma
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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:
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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
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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)
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
| 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 | 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 | |
| Principal Investigator: | Alex F Herrera | City of Hope Comprehensive Cancer Center |
| Responsible Party: | City of Hope Medical Center |
| ClinicalTrials.gov Identifier: | NCT03113500 |
| Other Study ID Numbers: |
17058 NCI-2017-00573 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 17058 ( Other Identifier: City of Hope Medical Center ) P30CA033572 ( U.S. NIH Grant/Contract ) |
| First Posted: | April 13, 2017 Key Record Dates |
| Last Update Posted: | July 13, 2020 |
| Last Verified: | May 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 Daunorubicin Podophyllotoxin Antineoplastic Agents, Immunological Antibodies Immunoglobulins |