NCT01950364

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2013

Geographic Reach
3 countries

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 23, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 25, 2013

Completed
1 month until next milestone

Study Start

First participant enrolled

November 1, 2013

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2014

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2015

Completed
8 months until next milestone

Results Posted

Study results publicly available

February 9, 2016

Completed
Last Updated

May 11, 2016

Status Verified

March 1, 2016

Enrollment Period

11 months

First QC Date

September 23, 2013

Results QC Date

October 30, 2015

Last Update Submit

March 30, 2016

Conditions

Hodgkin LymphomaAnaplastic Large-cell Lymphoma

Keywords

LymphomaHodgkinAnaplastic Large-cellRelapsedRefractoryAntigens, CD30Antibody-Drug ConjugateAntibodies, MonoclonalLymphoma, Non-HodgkinLymphoma, Large-Cell, AnaplasticMonomethyl auristatin EDrug TherapyImmunotherapyHematologic Diseases

Outcome Measures

Primary Outcomes (41)

  • 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).

    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.

    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.

    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.

    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.

    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.

    Cycle 3: 0.5 hour postdose

  • Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at 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.

    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.

    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.

    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.

    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.

    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.

    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.

    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.

    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.

    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.

    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.

    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.

    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.

    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.

    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.

    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.

    Cycle 1: Predose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 1: 0-24 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 1: 24-48 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 1: 48-72 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 1: 72-96 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 1: 96-120 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 1: 120-144 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 1: 144-168 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 1: 336-360 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 1: 480-504 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 3: Predose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 3: 0-24 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 3: 24-48 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 3: 48-72 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 3: 72-96 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 3: 96-120 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 3: 120-144 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 3: 144-168 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 3: 336-360 hours postdose

  • Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at 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.

    Cycle 3: 480-504 hours postdose

Secondary Outcomes (6)

  • 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

  • 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

  • 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)

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

    Day 1 of Cycle 1 and 3

  • Number of Participants With Markedly Abnormal Laboratory Values

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

  • +1 more secondary outcomes

Study Arms (2)

Arm A: Brentuximab vedotin

EXPERIMENTAL

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

Drug: brentuximab vedotin

Arm B: Brentuximab vedotin and rifampicin

EXPERIMENTAL

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.

Drug: Brentuximab vedotin and rifampicin

Interventions

brentuximab vedotinDRUG

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

Also known as: SGN-35
Arm A: Brentuximab vedotin
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.

Also known as: SGN-35
Arm B: Brentuximab vedotin and rifampicin

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Unknown Facility

Brussels, Belgium

Location

Unknown Facility

Ghent, Belgium

Location

Unknown Facility

Vilnius, Lithuania

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Salamanca, Spain

Location

MeSH Terms

Conditions

Hodgkin DiseaseLymphoma, Large-Cell, AnaplasticLymphomaRecurrenceLymphoma, Non-HodgkinHematologic Diseases

Interventions

Brentuximab VedotinRifampin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, T-CellDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

OligopeptidesPeptidesAmino Acids, Peptides, and ProteinsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulinsRifamycinsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsLactams, MacrocyclicMacrocyclic CompoundsPolycyclic Compounds

Results Point of Contact

Title
Medical Director
Organization
Takeda
trialdisclosures@takeda.com
+1-877-825-3327

Study Officials

  • Medical Monitor

    Millennium Pharmaceuticals, Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 23, 2013

First Posted

September 25, 2013

Study Start

November 1, 2013

Primary Completion

October 1, 2014

Study Completion

June 1, 2015

Last Updated

May 11, 2016

Results First Posted

February 9, 2016

Record last verified: 2016-03

Locations

BE(2)LI(1)ES(3)