A Study of Brentuximab Vedotin in Patients With Hodgkin Lymphoma Unsuitable for Chemotherapy Due to Age, Frailty or Co-morbidity

• Status: Completed
• Trial end date: 2017-10-02
• Target enrollment: 0
• Participant gender: All

Summary

An early phase II, single arm, two stage study, to investigate the level of activity, duration of response and tolerability of brentuximab vedotin (SGN-35), as a single agent, utilising a response adapted approach, in older, frailer or co-morbid patients with previously untreated Hodgkin lymphoma.

Opened Feb 2014 and will recruit over 18 months. Duration of treatment will be dependent on the patients' response (see schema below) with a maximum of 16 cycles over 48 weeks.

At the end of treatment patients will be assessed clinically at 3 months intervals and by CT scan at 15, 18, 24 and 36 months. For those still alive and disease free after 2 years, follow-up will be according to local practice.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Birmingham
• Collaborators: Leukaemia Lymphoma Research; Millennium Pharmaceuticals, Inc.
• Treatments: Antibodies, Monoclonal; Brentuximab Vedotin

Criteria

Inclusion Criteria:

1. Histologically confirmed CD30 positive classical Hodgkin lymphoma

2. No previous treatment for classical Hodgkin lymphoma

3. Aged ≥ 16 years

4. Stages II (with B symptoms, extranodal disease, bulky disease, ≥3 sites of nodal involvement, fewer than 3 sites of nodal involvement but unsuitable for radiotherapy because of anatomical distribution or ESR ≥50 mm/h), III and IV classical Hodgkin lymphoma

5. Any of the following:

At any age and with ECOG score of 0, 1, 2 or 3, for whom standard chemotherapy considered inappropriate because:

• Impaired cardiac function defined either by an ejection fraction of < 50% assessed by echocardiogram or nuclear medicine scan (MUGA)

• Left ventricular ejection fraction ≥50% measured by echocardiography or MUGA but in the presence of significant co-morbidities or cardiac risk factors such as diabetes mellitus, hypertension, peripheral vascular disease, ischaemic heart disease, previous myocardial infarction, obesity, stroke or transient ischaemic attacks (TIA) that make anthracycline-containing chemotherapy inadvisable as determined by the investigator.

• Heart failure clinically determined by the presence of New York Heart Association (NYHA) heart failure grade II and III due to a cause other than Hodgkin Lymphoma

• Impaired respiratory function with DLCO and/or FVC/FEV1 ratio <75% of predicted due to a cause other than Hodgkin lymphoma

For patients aged 60 years or older,

• an ECOG score of 1, 2 or 3 for any reason, before the start of permitted steroids (see section 7.9) and considered unsuitable for treatment with standard chemotherapy by the investigator

All co-morbidities must be documented on the baseline form and the CIRS-G score (if 60 years or older) recorded.

6. FDG avid disease - proven by PET scan

7. Measurable disease with at least one lesion measuring >1.5 cm in long axis diameter (for nodal lesions) or >1.0cm in long axis diameter (for extra-nodal lesions)

8. Written informed consent

9. Able to comply with requirements of the protocol (including PET scans)

10. Agree and be able to use adequate contraception if required

Exclusion Criteria:

1. Nodular lymphocyte predominant Hodgkin lymphoma

2. Grade 2 or worse peripheral neuropathy

3. Haemoglobin <90 g/L (transfusion allowed)

4. Unsupported neutrophil count <1.0 x 109/l and platelet count <100 x 109/l unless due to bone marrow infiltration by Hodgkin lymphoma demonstrated by trephine biopsy

5. Serum bilirubin ≥1.5 times upper limit normal unless due to Hodgkin lymphoma or Gilbert's syndrome

6. Creatinine clearance <30 ml/min (calculated by the modified Cockroft-Gault formula, see appendix) unless due to Hodgkin lymphoma. Patients with an eGFR <30 ml/min but a measured GFR by another method (e.g. EDTA) of 30ml/min or greater would be eligible.

7. Pregnant or lactating women

8. Any other cancer diagnosis within the last 24 months - except for:

• Appropriately treated superficial melanoma, basal cell carcinoma and squamous cell carcinoma of the skin

• Appropriately treated cervical intra-epithelial neoplasia

• In situ or organ confined prostate cancer not currently requiring therapy

Previous cancers treated with curative intent and with no evidence of recurrence following a minimum of at least 2 years of follow-up are permitted.

9. The use of other investigational or anti-neoplastic agents within the previous 6 weeks or during the trial.

10. Known to be HIV, Hep B positive (Hep B Core antibody positive allows inclusion providing surface / core antigen both negative) or Hep C positive (Hep C antibody positive allows inclusion providing PCR for viral RNA is negative).

11. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin.

12. Known cerebral or meningeal involvement by Hodgkin lymphoma

13. Symptoms or signs of progressive multifocal leukoencephalopathy (PML)

14. Any active systemic viral, bacterial, or fungal infection requiring intravenous antimicrobials within 2 weeks prior to registration

15. Evidence of current uncontrolled cardiovascular conditions, including unstable angina and NYHA grade IV heart failure

16. ECOG 4 at registration