Bendamustine Plus Brentuximab Vedotin in HL and CD30+ PTCL in First Salvage Setting

NCT02499627 | Terminated Phase 2

• 1 other identifier: FIL-BBV
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 5

Brief Summary

This is a single-arm, open-label, multicenter, phase 2 clinical trial aimed at evaluating the efficacy and safety of the combination of bendamustine and brentuximab vedotin as a first salvage therapy in patients with relapsed or refractory Hodgkin's lymphoma or PTCL. A total of 25 patients with PTCL, and 40 with Hodgkin's lymphoma are expected to be treated according to this treatment protocol.

Conditions

Lymphatic Diseases

Keywords

Lymphoma; Hodgkin; PTCL; CD30+

Outcome Measures

Primary Outcomes (1)

• Overall objective response rate (ORR).

  Proportion of patients in CR or PR

  1 year

Secondary Outcomes (5)

• Duration of the response (DOR)

  1 year

• Complete remission (CR) rate

  1 year

• Progression-free survival (PFS)

  1 year

• Adverse Events

  1 year

• Overall survival (OS)

  1 year

Other Outcomes (3)

• One-year event-free survival (EFS)

  1 year

• B symptoms resolution rate (when documented at presentation)

  1 year

• CD30 expression and the objective response

  1 year

Study Arms (1)

Bendamustine + Brentuximab for 6 cycles

EXPERIMENTAL

Bendamustine 90 mg/m2 d1-2. Brentuximab vedotin 1.8 mg/kg d1.Every 21 days for 6 cycles.

Drug: Brentuximab Vedotin; Drug: Bendamustine

Interventions

Brentuximab Vedotin DRUG

Brentuximab will be given intravenously at a total dose of 1.8 mg/kg on day 1 of each 21 days-based cycle, for 6 cycles.

Also known as: SGN35

Bendamustine + Brentuximab for 6 cycles

Bendamustine DRUG

Bendamustine will be administered at a dose of 90 mg/m2 on day 1 and 2 of each 21 days-based cycle, for 6 cycles.

Also known as: Levact

Bendamustine + Brentuximab for 6 cycles

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with primary refractory disease after one previous line of therapy or at first relapse after one previous line of therapy. Patients must have completed any prior treatment with radiation, chemotherapy, biologics, immunotherapy and/or other investigational agents at least 4 weeks prior to the first BBV dose
• Histologically-confirmed CD30+ disease (IHC BerH2 antibody)
• Age from 18 to 60 years.
• Fluorodeoxyglucose (FDG)-avid and measurable disease (lymph nodes must have long axis of 1.5 cm regardless of short axis or long axis 1.1 to 1.5 and short axis \> 1.0 cm) as documented by both PET and CT.
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• The following required baseline laboratory data: absolute neutrophil count (ANC) ≥ 1500/μL, unless known marrow involvement due to disease, platelets ≥ 75,000/μL, unless known marrow involvement due to disease, bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN for patients with Gilbert's disease, serum creatinine ≤ 1.5 X ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 X ULN.
• Serum Albumin ≥ 3 g/dL.
• Females of childbearing potential must have a negative serum or urine β-hCG pregnancy test result within 7 days prior to the first dose of therapy. Females of non-childbearing potential are those who are postmenopausal for more than 1 year or who have had a bilateral tubal ligation or hysterectomy.
• Both females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for at least 6 months following the last dose of study drug.
• Male patients, even if surgically sterilized (i.e., post vasectomy), who:
• Agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of the study drug, or
• Agree to completely abstain from heterosexual intercourse.
• Patients must provide written informed consent

You may not qualify if:

• Previous treatment with bendamustine or brentuximab vedotin.
• Prior autologous stem cell transplant.
• Known history of any of the following cardiovascular conditions: myocardial infarction within 2 years of study entry; NYHA class III or IV heart failure; cardiac arrhythmias; angina; any electrocardiographic evidence of acute ischemia or conduction system abnormalities; recent evidence (within 6 months before the first dose of study drug) of a left-ventricular ejection fraction \< 50%.
• History of another primary malignancy for within 3 years of study entry (the following are exempt from the 3-year limit: non-melanoma skin cancer, curatively treated localized prostate cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear).
• Known cerebral/meningeal disease (HL or any other etiology) or testicular involvement.
• Signs or symptoms of progressive multifocal leukoencephalopathy (PML).
• Pre-existing Peripheral Neuropathy ≥ 2.
• Any active systemic viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 2 weeks prior to the first dose of therapy.
• Current therapy with other systemic anti-neoplastic or investigational agents.
• Therapy with corticosteroids at greater than or equal to 20 mg/day prednisone equivalent within 1 week prior to the first dose of therapy.
• Women who are pregnant or breastfeeding.
• Patients with a known hypersensitivity to recombinant proteins, murine proteins, or any excipient contained in the drug formulation of brentuximab vedotin and to bendamustine.
• HIV positive.
• HCV positive.
• HBsAg positive; HBsAg negative patients with anti-HBcAg positive can be enrolled if HBV DNA is negative and antiviral treatment with Lamivudine or Tenofir is provided.

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (5)

A.O S.Orsola-Malpighi

Bologna, BO, 40138, Italy

Location

Spedali Civili

Brescia, BS, 25123, Italy

Location

Fondazione IRCCS Milano INT

Milan, MI, 20133, Italy

Location

AOU Città della Salute e della Scienza

Torino, TO, 10126, Italy

Location

IRCCS Fondazione Pascale

Napoli, 80131, Italy

Location

MeSH Terms

Conditions

Lymphatic Diseases; Lymphoma

Interventions

Brentuximab Vedotin; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Vittorio Stefoni, MD

  Ematologia "L. & A. Seragnoli" - Policlinico S. Orsola Malpighi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2015
• First Posted: July 16, 2015
• Study Start: December 23, 2015
• Primary Completion: September 13, 2019
• Study Completion: June 30, 2020
• Last Updated: May 27, 2021

Record last verified: 2020-09

Locations

IT (5)