Clinical trial NCT01950364: A Phase 1 Study in Patients With Relapsed or Refractory Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma
Official title: A Phase 1 Study to Estimate MMAE Metabolites in Human Plasma and Urine in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma or Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma Receiving Brentuximab Vedotin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hodgkin Lymphoma
Anaplastic Large-cell Lymphoma
Keywords: Lymphoma
Hodgkin
Anaplastic Large-cell
Relapsed
Refractory
Antigens, CD30
Antibody-Drug Conjugate
Antibodies, Monoclonal
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Anaplastic
Monomethyl auristatin E
Drug Therapy
Immunotherapy
Hematologic Diseases
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2013-09-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label trial to estimate the concentrations of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma (HL) or relapsed/refractory systemic anaplastic large cell lymphoma (sALCL) participants treated with either brentuximab vedotin or brentuximab vedotin + rifampicin.


Eligibility criteria: Inclusion Criteria:

* Male or female participants between 18 years and 75 years old, with relapsed or refractory HL or relapsed or refractory sALCL who have previously received at least 1 multiagent chemotherapy
* Measurable disease
* An Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1
* Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 30 days after the last dose of study drug, or agree to practice true abstinence
* Male participants who agree to practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug or agree to practice true abstinence
* Clinical laboratory values as specified in the study protocol

Exclusion Criteria:

* Participants for whom rifampicin is contraindicated
* Previously received an allogeneic transplant.
* Participants with current diagnosis of primary cutaneous anaplastic large cell lymphoma (ALCL) (participants whose ALCL has transformed to sALCL are eligible).
* Known cerebral/meningeal disease including signs or symptoms of progressive multifocal leukoencephalopathy (PML)
* Female participants who are lactating and breastfeeding or pregnant
* Known human immunodeficiency virus (HIV) positive,
* Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection

Primary outcomes:
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose
timeFrame: Cycle 1: Predose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose
timeFrame: Cycle 2: Predose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose
timeFrame: Cycle 3: Predose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose
timeFrame: Cycle 1: 0.5 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose
timeFrame: Cycle 2: 0.5 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose
timeFrame: Cycle 3: 0.5 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 4 Hour Postdose
timeFrame: Cycle 1: 4 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 4 Hour Postdose
timeFrame: Cycle 3: 4 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 24 Hour Postdose
timeFrame: Cycle 1: 24 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 24 Hour Postdose
timeFrame: Cycle 3: 24 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 48 Hour Postdose
timeFrame: Cycle 1: 48 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 48 Hour Postdose
timeFrame: Cycle 3: 48 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 72 Hour Postdose
timeFrame: Cycle 1: 72 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 72 Hour Postdose
timeFrame: Cycle 3: 72 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 96 Hour Postdose
timeFrame: Cycle 1: 96 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 96 Hour Postdose
timeFrame: Cycle 3: 96 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 144 Hour Postdose
timeFrame: Cycle 1: 144 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 144 Hour Postdose
timeFrame: Cycle 3: 144 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 336 Hour Postdose
timeFrame: Cycle 1: 336 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 336 Hour Postdose
timeFrame: Cycle 3: 336 hour postdose
measure: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 480 Hour Postdose
timeFrame: Cycle 3: 480 hour postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, Predose
timeFrame: Cycle 1: Predose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 0-24 Hours Postdose
timeFrame: Cycle 1: 0-24 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 24-48 Hours Postdose
timeFrame: Cycle 1: 24-48 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 48-72 Hours Postdose
timeFrame: Cycle 1: 48-72 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 72-96 Hours Postdose
timeFrame: Cycle 1: 72-96 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 96-120 Hours Postdose
timeFrame: Cycle 1: 96-120 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 120-144 Hours Postdose
timeFrame: Cycle 1: 120-144 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 144-168 Hours Postdose
timeFrame: Cycle 1: 144-168 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 336-360 Hours Postdose
timeFrame: Cycle 1: 336-360 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 480-504 Hours Postdose
timeFrame: Cycle 1: 480-504 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, Predose
timeFrame: Cycle 3: Predose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 0-24 Hours Postdose
timeFrame: Cycle 3: 0-24 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 24-48 Hours Postdose
timeFrame: Cycle 3: 24-48 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 48-72 Hours Postdose
timeFrame: Cycle 3: 48-72 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 72-96 Hours Postdose
timeFrame: Cycle 3: 72-96 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 96-120 Hours Postdose
timeFrame: Cycle 3: 96-120 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 120-144 Hours Postdose
timeFrame: Cycle 3: 120-144 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 144-168 Hours Postdose
timeFrame: Cycle 3: 144-168 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 336-360 Hours Postdose
timeFrame: Cycle 3: 336-360 hours postdose
measure: Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 480-504 Hours Postdose
timeFrame: Cycle 3: 480-504 hours postdose
Secondary outcomes:
measure: Serum Concentrations of Antibody-drug Conjugate (ADC)
timeFrame: Cycle 1 and 3: Predose, 0.5, 4, 72, 336 hours post-dose; Cycle 2: Predose, 0.5 hours post-dose; Cycle 3: 480 hours post-dose
measure: Serum Concentration of Total Antibody (TAb)
timeFrame: Cycle 1 and 3: Predose, 0.5, 4, 72, 336 hours post-dose; Cycle 2: Predose, 0.5 hours post-dose; Cycle 3: 480 hours post-dose
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 30 days after last dose of study drug (30 days after Cycle 16)
measure: Number of Participants With Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin
timeFrame: Day 1 of Cycle 1 and 3
measure: Number of Participants With Markedly Abnormal Laboratory Values
timeFrame: Baseline up to 30 days after last dose of study drug (30 Days after Cycle 16)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline up to 30 days after last dose of study drug (30 Days after Cycle 16)
Other outcomes:
Locations:
city: Brussels
country: Belgium
city: Gent
country: Belgium
city: Vilnius
country: Lithuania
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Salamanca
country: Spain
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: