Hodgkin Lymphoma Treatment With Adcetris and Levact in the Old Patient

NCT02467946 | Completed Phase 1 DMC

• 1 other identifier: 2013/24
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment outcome with ABVD in elderly patients remains inferior to adults. Moreover, Bleomycin-induced lung toxicity in the elderly has been reported as high as 46%. For these reasons, questions arise whether ABVD could be still considered the standard treatment in HL patients aged \> than 60. Regimens containing other alkylators such as CHOP proved even superior to ABVD, with a 3-y PFS of 67%. Frontline treatment of advanced-stage HL with Brentuximab Vedotin (BV) in association with AVD (Doxorubicin, Vinblastine, Dacarbazine) proved very active in a pioneer study, reporting the preliminary results of a phase 1 multicentre trial, in which the percentage of patients achieving CR was as high as 92%. For all these reason the investigators decided to test the association of an alkylator with an innovative mechanism of action and a very safe toxicity profile in the elderly such as Bendamustine (Be) with BV in untreated elderly HL patients. The combination of BV and Be, investigated in this study, might represent an innovative treatment alternative for HL patients older than 60 years of age, especially for those of them in whom ABVD chemotherapy, the current standard front-line treatment, is not suitable. However, even when ABVD is given as upfront treatment for elderly HL patients, it is associated with substantial dose reduction, treatment delay, toxicity, and treatment-related mortality, with treatment outcomes remaining much inferior to those obtained in younger patients. This drug association is expected to be safe, well-tolerated and to demonstrate higher efficiency compared with ABVD. In this setting, it is expected that this therapy could be offered to the large majority of elderly patients with a full treatment completion reached in up to 80% of these patients. Thus, the aim of this study will be to assess safety and efficacy of the above association.

Conditions

Clinical Efficacy; Safety

Outcome Measures

Primary Outcomes (2)

• toxicity analysis

  To evaluate the tolerability and toxicity of Adcetris-Levact (BV-Be) association.

  up to 2.5 years

• Efficacy analysis

  To evaluate the efficacy in terms of Response Rate after treatment completion of Adcetris-Levact (BV-Be) association.

  up to 2.5 years

Secondary Outcomes (2)

• Progression Free Survival

  3 years

• Complete Response Rate

  2 years

Study Arms (1)

Adcetris-Levact (BV-Be) Association

EXPERIMENTAL

Adcetris® (BV) : 1.2 mg/kg intravenously every 3 weeks Levact® (Be): 90 mg/m2/day intravenously for 2 days every 3 weeks. Up to 6 cycles

Drug: Adcetris-Levact

Interventions

Adcetris-Levact DRUG

Association of Adcetris (1.2 mg/kg intravenously every 3 weeks) with Levact (90 mg/m2/day intravenously for 2 days every 3 weeks) during at least 6 cycles.

Also known as: Bendamustine, Brentuximab Vedotin

Adcetris-Levact (BV-Be) Association

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced classical Hodgkin Lymphoma according to the World Health Organization classification. All Hasenclever IPS prognostic groups accepted
• Stages IIB to IV B
• Age 60-80 years included
• Patient not previously treated
• ECOG ≤ 2
• Patient with adequate organ function:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Haemoglobin ≥ 9 g/dL
• Platelets (PTL) ≥ 100 x 109/L
• AST - ALAT ≤ 2.5x ULN
• Bilirubin ≤ 1.5 x ULN
• Creatinine \< 150 µmol/l (or 1.7 mg/dl)
• Male patients, even if surgically sterilized, (i.e., status post vasectomy) and women of childbearing potential agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
• Contraception as described above is not a requirement if the female patient's postmenopausal status is documented (has had no menstrual period for at least 12 consecutive months)
• Information delivered to patient and voluntary written informed consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

You may not qualify if:

• Patients aged less than 60 years.
• Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML.
• Symptomatic neurologic disease compromising instrumental activities of daily living or requiring medication.
• Symptomatic sensory or motor peripheral neuropathy.
• Chemotherapy, biologics, and/or other treatment with immunotherapy not completed at least 4 weeks prior to first dose of study drug.
• Patient who had major surgery less than 30 days before start of treatment
• Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose.
• Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of BV.
• Patient presenting an uncontrolled infectious disease, including active HBV infection defined by either detection of HBs Antigen or presence of anti HBc antibody without detectable anti HBs antibody or HIV or HCV serology positivity. In case of HBc positive serology, a PCR could be performed in order to determine viral load. Patients with viral load defined as negative could be included.
• o A prophylactic treatment will be strongly recommended (see HALO Study protocol, paragraph 6.2.3, page 36)
• Patient with history of poor compliance or current or past psychiatric conditions or severe acute or chronic medical conditions, or laboratory abnormalities that would interfere, in the judgment of the investigator and/or sponsor, with the ability to comply with the study protocol.
• Patients with uncompensated diabetes mellitus and fasting glucose levels over 180 mg/dl.
• Known history of any of the following cardiovascular conditions
• Myocardial infarction within 2 years of enrollment

Sponsors & Collaborators

• Centre Antoine Lacassagne: lead
• Millennium: The Takeda Oncology Company: collaborator

Study Sites (1)

Centre Antoine Lacassagne

Nice, 06000, France

Location

Related Links

• Related Info

MeSH Terms

Interventions

Bendamustine Hydrochloride; Brentuximab Vedotin

Intervention Hierarchy (Ancestors)

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; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: June 10, 2015
• Study Start: January 14, 2016
• Primary Completion: April 6, 2022
• Study Completion: April 6, 2022
• Last Updated: January 4, 2023

Record last verified: 2022-04

Locations

FR (1)