NCT03113500

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

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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
• 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

Interventions

Type	Name	Description
DRUG	Brentuximab Vedotin	Given IV
DRUG	Cyclophosphamide	Given IV
DRUG	Doxorubicin	Given IV
DRUG	Doxorubicin Hydrochloride	Given IV
DRUG	Etoposide	Given IV
DRUG	Etoposide Phosphate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Prednisone	Given PO

Timeline

• Start date: 2017-05-25
• Primary completion: 2021-07-16
• Completion: 2026-07-07
• First posted: 2017-04-13
• Last updated: 2025-11-14
• Results posted: 2023-04-19

Locations

5 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study