NCT02243436

Brentuximab Vedotin in Pre-transplant Induction and Consolidation for Relapsed or Refractory Hodgkin Lymphoma

Phase I-II Clinical Trial for the Evaluation of Brentuximab Vedotin Plus Etoposide, Solumoderin (Methylprednisolone), High Dose ARA-C (Cytarabine) and Cisplatin in the Transplant and Post-transplant Management for Relapsed or Refractory Classical Hodgkin Lymphoma Patients

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 67 (actual)
• Sponsor: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Phase I trial aimed to determine the Maximum Tolerable Dose of the BV in combination with ESHAP in relapsed/resistant Hodgkin Lymphona patients and to evaluate response to treatment with BV-ESHAP as salvage regimen prior to autologous stem cell transplantation.

Detailed description

Most patients suffering from Hodgkin's lymphoma (HL) can be successfully treated with standard chemo- and/or radiotherapy. However, in patients with refractory disease/relapsing after first line of therapy, conventional-dose chemotherapy regimens induce low remission rates, with long-term disease free survival not higher than 10% of patients. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard treatment for these patients. This treatment approach results in long-term remissions in approximately 40-50% of relapsed patients, and in up to 25-30% of those with primary refractory disease. The possibility of a cure depends on several prognostic factors, however, in almost all series, the strongest prognostic factor has been the disease status before ASCT. Patients with HL who do not achieve complete remission (CR) after induction chemotherapy and those with unresponsive relapse have a very poor prognosis. Therefore, the choice of a very active pre-transplant salvage chemotherapy regimen is extremely important to improve results after ASCT. In addition, this activity should also be combined with a good stem cell mobilizing potential and low toxicity profiled. Several pre-transplant salvage regimens for refractory/relapsed HL are currently used with an overall response (OR) and CR rates ranging from 60% to 88% and from 17% to 49%, respectively. No randomized trial exists comparing the effectiveness of these regimens. ESHAP (Etoposide, Solumoderin (methylprednisolone), Ara-C (Cytarabine) and cisplatin) is one of the most commonly used regimens. ESHAP induces an OR and CR of 73% and 41%, respectively, with 5% toxic deaths. In the present study, a combination of ESHAP plus Brentuximab Vedotin (BV) is proposed as pre-transplant therapy with the aim to improve the CR rate before ASCT. HL is characterized by the presence of CD30-positive Hodgkin Reed-Sternberg cells. The antibody-drug conjugate BV delivers the highly potent antimicrotubule agent monomethyl auristatin E (MMAE) to CD30-positive malignant cells by binding specifically to CD30 on the cell surface and releasing MMAE inside the cell via lysosomal degradation. Binding of MMAE to tubulin results in apoptotic death of the CD30 expressing tumor cell.

Conditions

• CLASSICAL HODGKIN LYMPHOMA

Interventions

Type	Name	Description
DRUG	Brentuximab Vedotin	Brentuximab Vedotin, 0.9mg/kg, 1.2mg/kg, 1.8mg/kg, day 1
DRUG	Etoposide	Intravenose use, 40mg/m2/day, on days 1 to 4
DRUG	Soludomerin	Intravenous use, 250mg/day, on days 1 to 4
DRUG	Cisplatin	Intravenous use, 25mg/m2/day, on days 1 to 4
DRUG	Ara C	Intravenous use, 2g/m2, day 5

Timeline

• Start date: 2014-11-11
• Primary completion: 2019-01-01
• Completion: 2019-01-14
• First posted: 2014-09-18
• Last updated: 2019-04-24

Locations

14 sites across 1 country: Spain