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

Phase 1

Completed

• Conditions: Hodgkin Lymphoma; Anaplastic Large-cell Lymphoma
• Interventions: Drug: Brentuximab vedotin and rifampicin; Drug: brentuximab vedotin

• Registration Number: NCT01950364
• Lead Sponsor: Millennium Pharmaceuticals, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-09-23
• Study First Submitted QC: 2013-09-24
• Study First Posted: 2013-09-25
• Study Start: 2013-11
• Primary Completion: 2014-10
• Study Completion: 2015-06
• Results First Submitted: 2015-10-30
• Results First Submitted QC: 2016-01-06
• Results First Posted: 2016-02-09
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-30
• Last Update Posted: 2016-05-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B: Brentuximab vedotin and rifampicin	Brentuximab vedotin and rifampicin	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.
Arm A: Brentuximab vedotin	brentuximab vedotin	Brentuximab vedotin will be administered every 3 weeks at a dose of 1.8 mg/kg.

Primary Outcome Measures

Name	Time	Method
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 336 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 336 Hour Postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, Predose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 0-24 Hours Postdose	Cycle 1: 0-24 hours postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose	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).
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 96 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose	Cycle 2: Predose	Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 4 Hour Postdose	Cycle 1: 4 hour postdose	Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 4 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 72 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 72 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 96 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose	Cycle 3: Predose	Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 24 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 24 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 48 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 48 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 144 Hour Postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 480 Hour Postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 24-48 Hours Postdose	Cycle 1: 24-48 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 48-72 Hours Postdose	Cycle 1: 48-72 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 96-120 Hours Postdose	Cycle 1: 96-120 hours postdose	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.
Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 144 Hour Postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 72-96 Hours Postdose	Cycle 1: 72-96 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 0-24 Hours Postdose	Cycle 3: 0-24 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 24-48 Hours Postdose	Cycle 3: 24-48 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 120-144 Hours Postdose	Cycle 3: 120-144 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 336-360 Hours Postdose	Cycle 3: 336-360 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 120-144 Hours Postdose	Cycle 1: 120-144 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 144-168 Hours Postdose	Cycle 1: 144-168 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 336-360 Hours Postdose	Cycle 1: 336-360 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 480-504 Hours Postdose	Cycle 1: 480-504 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, Predose	Cycle 3: 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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 48-72 Hours Postdose	Cycle 3: 48-72 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 72-96 Hours Postdose	Cycle 3: 72-96 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 96-120 Hours Postdose	Cycle 3: 96-120 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 144-168 Hours Postdose	Cycle 3: 144-168 hours postdose	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.
Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 480-504 Hours Postdose	Cycle 3: 480-504 hours postdose	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Markedly Abnormal Laboratory Values	Baseline up to 30 days after last dose of study drug (30 Days after Cycle 16)	The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Baseline up to 30 days after last dose of study drug (30 Days after Cycle 16)	Vital signs included body temperature, body weight, blood pressure and heart rate.
Serum Concentrations of Antibody-drug Conjugate (ADC)	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	The LLQ for all the observations was 12.5 ng/mL.
Number of Participants With Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Day 1 of Cycle 1 and 3	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.
Serum Concentration of Total Antibody (TAb)	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	The LLQ for all the observations was 12.5 ng/mL.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Baseline up to 30 days after last dose of study drug (30 days after Cycle 16)	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.