A Phase 1 Study in Patients With Relapsed or Refractory Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma

Phase 1CompletedNCT01950364

Millennium Pharmaceuticals, Inc.20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hodgkin Lymphoma Anaplastic Large-cell Lymphoma

Interventions

brentuximab vedotinDRUG

Brentuximab vedotin will be administered every 3 weeks at a dose of 1.8 mg/kg.

Brentuximab vedotin and rifampicinDRUG

Brentuximab vedotin will be administered every 3 weeks at a dose of 1.8 mg/kg beginning on Cycle 1, Day 1; daily rifampicin (600 mg PO) will be administered during Cycles 0 through 3 only, beginning on Cycle 0, Day 1 (7 days before the Cycle 1, Day 1 dose of brentuximab vedotin) and continuing through Cycle 3, Day 21.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (6)

Unnamed facility

Brussels, Belgium

Unnamed facility

Ghent, Belgium

Unnamed facility

Vilnius, Lithuania

Unnamed facility

Barcelona, Spain

Unnamed facility

Madrid, Spain

Outcomes

Primary Outcomes

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The lower limit of Quantification (LLQ) for all the observations was 0.01 nanogram/milliliter (ng/mL).

Time frame: Cycle 1: Predose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 2: Predose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 3: Predose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 1: 0.5 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 2: 0.5 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 3: 0.5 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 4 Hour Postdose

Data from ClinicalTrials.gov

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Unnamed facility

Salamanca, Spain

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 1: 4 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 4 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 3: 4 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 24 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 1: 24 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 24 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 3: 24 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 48 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 1: 48 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 48 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 3: 48 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 72 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 1: 72 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 72 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 3: 72 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 96 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 1: 96 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 96 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 3: 96 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 144 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 1: 144 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 144 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 3: 144 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 336 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 1: 336 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 336 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 3: 336 hour postdose

Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 480 Hour Postdose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.

Time frame: Cycle 3: 480 hour postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, Predose

Metabolites of MMAE includes C4, C5, C7, C8 and C13. Amount of MMAE and its metabolites in urine were determined by multiplying the volume of urine obtained and the concentration of MMAE and its metabolites present in it, respectively. The LLQ for determining the concentration was 0.01 ng/mL.

Time frame: Cycle 1: Predose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 0-24 Hours Postdose

Time frame: Cycle 1: 0-24 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 24-48 Hours Postdose

Time frame: Cycle 1: 24-48 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 48-72 Hours Postdose

Time frame: Cycle 1: 48-72 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 72-96 Hours Postdose

Time frame: Cycle 1: 72-96 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 96-120 Hours Postdose

Time frame: Cycle 1: 96-120 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 120-144 Hours Postdose

Time frame: Cycle 1: 120-144 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 144-168 Hours Postdose

Time frame: Cycle 1: 144-168 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 336-360 Hours Postdose

Time frame: Cycle 1: 336-360 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 480-504 Hours Postdose

Time frame: Cycle 1: 480-504 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, Predose

Time frame: Cycle 3: Predose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 0-24 Hours Postdose

Time frame: Cycle 3: 0-24 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 24-48 Hours Postdose

Time frame: Cycle 3: 24-48 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 48-72 Hours Postdose

Time frame: Cycle 3: 48-72 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 72-96 Hours Postdose

Time frame: Cycle 3: 72-96 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 96-120 Hours Postdose

Time frame: Cycle 3: 96-120 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 120-144 Hours Postdose

Time frame: Cycle 3: 120-144 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 144-168 Hours Postdose

Time frame: Cycle 3: 144-168 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 336-360 Hours Postdose

Time frame: Cycle 3: 336-360 hours postdose

Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 480-504 Hours Postdose

Time frame: Cycle 3: 480-504 hours postdose

Secondary Outcomes

Serum Concentrations of Antibody-drug Conjugate (ADC)

The LLQ for all the observations was 12.5 ng/mL.

Time frame: 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

Serum Concentration of Total Antibody (TAb)

The LLQ for all the observations was 12.5 ng/mL.

Time frame: 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

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. AEs included both SAE and non-SAE.

Time frame: Baseline up to 30 days after last dose of study drug (30 days after Cycle 16)

Number of Participants With Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin

Participants with positive ATA at both Cycle 1 and 3, negative ATA at both Cycle 1 and 3, and transient positive (positive at one time point, but negative at the other) ATA for brentuximab vedotin were reported.

Time frame: Day 1 of Cycle 1 and 3

Number of Participants With Markedly Abnormal Laboratory Values

The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.

Time frame: Baseline up to 30 days after last dose of study drug (30 Days after Cycle 16)

Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Vital signs included body temperature, body weight, blood pressure and heart rate.

Time frame: Baseline up to 30 days after last dose of study drug (30 Days after Cycle 16)