Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 38 of 1216 for:    "Hodgkin lymphoma"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02243436
Recruitment Status : Active, not recruiting
First Posted : September 18, 2014
Last Update Posted : February 8, 2019
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

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.

Condition or disease Intervention/treatment Phase
CLASSICAL HODGKIN LYMPHOMA Drug: Brentuximab Vedotin Drug: Etoposide Drug: Soludomerin Drug: Cisplatin Drug: Ara C Phase 1 Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 11, 2014
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019


Arm Intervention/treatment
Experimental: BV-ESHAP
  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
Brentuximab Vedotin, 0.9mg/kg, 1.2mg/kg, 1.8mg/kg, day 1
Other Name: ADCETRIS

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

Drug: Soludomerin
Intravenous use, 250mg/day, on days 1 to 4
Other Name: Methylprednisolone

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

Drug: Ara C
Intravenous use, 2g/m2, day 5
Other Name: Cytarabine




Primary Outcome Measures :
  1. Recommended dose [ Time Frame: Day 21 of cycle 1 (3 weeks after start of treatment) ]
    During phase I, defined as the maximum Tolerable Dose of the BV in combination with ESHAP in relapsed/resistant HL patients.

  2. Global response rate prior to ASCT [ Time Frame: 9 weeks (after start of treatment) ]
    During phase II, Global response rate after BV-ESHAP as salvage regimen prior to ASCT.

  3. Complete response [ Time Frame: 9 weeks (after start of treatment) ]
    Percentage of patients with complete response rate after BV-ESHAP as salvage regimen prior to ASCT.


Secondary Outcome Measures :
  1. Toxicity according to the CTC criteria [ Time Frame: 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. ]
    To determine the toxicity of BV-ESHAP regimen

  2. Stem cell mobilization capacity [ Time Frame: After first or second cycle of treatment ]
    To assess the stem cell mobilization capacity of the BV-ESHAP regimen: determine the expanse and effectiveness of the extraction of stem cells from peripheral blood.

  3. Transplant-related mortality (TRM) [ Time Frame: 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. ]
  4. Overall Survival (OS) [ Time Frame: 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. ]
    Percentage of patients alive after first dose of treatment through follow-up

  5. Progression free survival (PFS) [ Time Frame: 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. ]
    Percentage of patients without progression of disease

  6. Event-Free Survival [ Time Frame: 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. ]
    Percentage of patients without event

  7. Time to HL Progression [ Time Frame: 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. ]
  8. Disease-Free Survival [ Time Frame: 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. ]
  9. Response Duration [ Time Frame: 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. ]
    Length of time between date of evidenced response and progression of disease or death

  10. Lymphoma-Specific Survival [ Time Frame: 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. ]
  11. Time to Next Treatment [ Time Frame: 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. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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
  • Serum creatinine: < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute
  • Serum sodium >130 mmol/L
  • Voluntary written informed consent

Exclusion Criteria:

  • 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
  • Positive serology for HCV

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02243436


Locations
Layout table for location information
Spain
Hospital Universitario Central de Asturias
Oviedo, Asturias, Spain, 33006
Institut Català d'Oncologia, Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Institut Català d'Oncologia, Hospital Duran i Reynals
L'Hospitalet de Llobregat, Barcelona, Spain, 08908
Hospital Son Espases
Palma, Islas Baleares, Spain
Hospital del Mar
Barcelona, Spain, 08003
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Hospital General Universitario Gregorio Marañon
Madrid, Spain, 28007
Hospital Universitario Ramón y Cajal
Madrid, Spain, 28034
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital Universitario de Salamanca
Salamanca, Spain, 37007
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Spain, 38320
Hospital Universitario Virgen del Rocío
Sevilla, Spain, 41013
Hospital Clínico de Valencia
Valencia, Spain, 46010
Sponsors and Collaborators
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Millennium Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Chair: Ramón García-Sanz, MD Hospital Universitario de Salamanca

Layout table for additonal information
Responsible Party: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
ClinicalTrials.gov Identifier: NCT02243436     History of Changes
Other Study ID Numbers: BRESHAP-GELTAMO.LH-2013
2014-000835-17 ( EudraCT Number )
First Posted: September 18, 2014    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea:
CLASSICAL HODGKIN LYMPHOMA
HODGKIN LYMPHOMA
LYMPHOMA
HL

Additional relevant MeSH terms:
Layout table for MeSH terms
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cisplatin
Etoposide
Etoposide phosphate
Cytarabine
Methylprednisolone Hemisuccinate
Prednisolone
Antibodies, Monoclonal
Methylprednisolone
Methylprednisolone Acetate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents