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

NCT02243436 | Completed Phase 1

• 2 other identifiers: BRESHAP-GELTAMO.LH-20132014-000835-17
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 14

Brief 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.

Conditions

CLASSICAL HODGKIN LYMPHOMA

Keywords

CLASSICAL HODGKIN LYMPHOMA; HODGKIN LYMPHOMA; LYMPHOMA; HL

Outcome Measures

Primary Outcomes (3)

• Recommended dose

  During phase I, defined as the maximum Tolerable Dose of the BV in combination with ESHAP in relapsed/resistant HL patients.

  Day 21 of cycle 1 (3 weeks after start of treatment)

• Global response rate prior to ASCT

  During phase II, Global response rate after BV-ESHAP as salvage regimen prior to ASCT.

  9 weeks (after start of treatment)

• Complete response

  Percentage of patients with complete response rate after BV-ESHAP as salvage regimen prior to ASCT.

  9 weeks (after start of treatment)

Secondary Outcomes (11)

• Toxicity according to the CTC criteria

  Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.

• Stem cell mobilization capacity

  After first or second cycle of treatment

• Transplant-related mortality (TRM)

  Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.

• Overall Survival (OS)

  Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.

• Progression free survival (PFS)

  Prior every cycle, 14th day of first three cycles, at week 12, 16, 19, 22, 25, 31. Every 12 weeks for 2 years and then every 24 week up to 5 years.

Study Arms (1)

BV-ESHAP

EXPERIMENTAL

1. \- 3 cycles every 21 days: * Brentuximab Vedotin, on day 1 (BV will be administered at three different doses 0.9mg/kg, 1.2mg/kg, 1.8mg/kg) * Etoposide 40 mg/m2/day, on days 1 to 4 * Soludomerin (methylprednisolone) 250 mg/day, on days 1 to 4 * Cisplatin 25 mg/m2/day, on days 1 to 4 * Ara C (cytarabine) 2 g/m2, on day 5 2. \- A fourth dose of BV will be given 21 days after the third BV dose during the evaluation of response before the transplant. 3. \- Autologous peripheral blood stem cell transplant 4. \- A fifth dose of BV (1.8mg/kg) will be given on between day 28 and 35 post-transplant, followed by two additional doses (1.8mg/kg) every 3 weeks, to complete a total of 7 BV infusions.

Drug: Brentuximab Vedotin; Drug: Etoposide; Drug: Soludomerin; Drug: Cisplatin; Drug: Ara C

Interventions

Brentuximab Vedotin DRUG

Brentuximab Vedotin, 0.9mg/kg, 1.2mg/kg, 1.8mg/kg, day 1

Also known as: ADCETRIS

BV-ESHAP

Etoposide DRUG

Intravenose use, 40mg/m2/day, on days 1 to 4

BV-ESHAP

Soludomerin DRUG

Intravenous use, 250mg/day, on days 1 to 4

Also known as: Methylprednisolone

BV-ESHAP

Cisplatin DRUG

Intravenous use, 25mg/m2/day, on days 1 to 4

BV-ESHAP

Ara C DRUG

Intravenous use, 2g/m2, day 5

Also known as: Cytarabine

BV-ESHAP

Eligibility Criteria

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

You may qualify if:

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Histologically confirmed relapsed or refractory classical HL after first line chemotherapy. CD30 has to be positive
• Age 18 to 65 years. Patient \>65 years old with ECOG ≤1 and absence of comorbidities will be included in the study
• ECOG ≤2
• Karnofsky performance status ≥ 60
• No major organ dysfunction
• Biopsy at HL relapse or when refractoriness disease is diagnosed must be done prior to BV-ESHAP. If biopsy cannot be performed, tumor biopsy at initial diagnosis of HL must be available to be revised
• Absence of prior history of other malignant diseases, except:
• Basal cell carcinoma of the skin or uterine "in situ" carcinoma adequately treated Any curable neoplasia adequately treated that has achieved complete response and has remained in such status longer than 3 years
• Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse
• Male patients, even if surgically sterilized, 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
• Life-expectancy \>3 months
• Platelet count ≥75•109/L (or 20 if due to Bone Marrow \[BM\] infiltration) absolute neutrophil count ≥1.5•109/L (or 0.5 if due to BM infiltration), and hemoglobin ≥ 8g/dL
• Total Bilirubin: \<1.5 x UNL, unless clearly related to the disease (Gilbert disease will be ruled out from this point)
• AST and ALT: \<3 xUNL except liver infiltration

You may not qualify if:

• Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Patients that have been treated previously with anti-CD30 monoclonal antibodies
• Myocardial infarction within 6 months prior to enrollment. Heart failure NYHA Class III-IV, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Recent evidence (within 6 months) of a left-ventricular ejection fraction \<50%
• Peripheral neuropathy or neuropathic pain grade ≥ 2
• Known cerebral or meningeal disease, including signs or symptoms of PML
• Symptomatic neurologic disease compromising normal activities of daily living or requiring medication
• Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in brentuximab vedotin
• Pregnant women or in breast-feeding period, or adults in childbearing period not using an effective contraception method
• Treatment with any known non-marketed drug substance or experimental therapy within the longer of 5 terminal half-lives or 4 weeks prior to enrollment or currently participating in any other interventional clinical study
• Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment within two weeks prior to first study drug dose
• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
• HIV positive
• Significant concurrent, uncontrolled medical condition which may represent a risk for the patient
• Positive serology for HBV

Sponsors & Collaborators

• Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (14)

Hospital Son Espases

Palma, Balearic Islands, Spain

Location

Institut Català d'Oncologia, Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Institut Català d'Oncologia, Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33006, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, 38320, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma

Interventions

Brentuximab Vedotin; Etoposide; Methylprednisolone; Cisplatin; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; 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; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Ramón García-Sanz, MD

  University of Salamanca

  STUDY CHAIR

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: August 27, 2014
• First Posted: September 18, 2014
• Study Start: November 11, 2014
• Primary Completion: January 1, 2019
• Study Completion: January 14, 2019
• Last Updated: April 24, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (14)