Phase 1
N=20
A Phase 1 Study in Patients With Relapsed or Refractory Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma
Hodgkin Lymphoma · Anaplastic Large-cell Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT01950364 ↗Enrolled (actual)
20
Serious AEs
20.0%
Results posted
Feb 2016
Primary outcome: Primary: Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose — NA; NA; NA; NA ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- brentuximab vedotin (Drug); Brentuximab vedotin and rifampicin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Millennium Pharmaceuticals, Inc.
- Primary completion
- Oct 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose |
NA; NA; NA; NA; NA; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose |
0.0919; 0.0795; NA; NA; NA; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose |
0.1046; 0.0727; NA; NA; NA; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose |
0.3902; 0.2149; 0.0184; NA; NA; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose |
0.3119; 0.2929; NA; NA; NA; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose |
0.3307; 0.2577; 0.0256; NA; NA; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 4 Hour Postdose |
2.2778; 1.7836; 0.0547; NA; 0.0254; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 4 Hour Postdose |
1.7171; 1.4529; 0.0397; NA; 0.0163; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 24 Hour Postdose |
3.7950; 3.1227; 0.0443; 0.0191; 0.0218; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 24 Hour Postdose |
3.2336; 2.2558; 0.0200; NA; 0.0203; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 48 Hour Postdose |
4.2140; 3.3727; 0.0424; 0.0128; 0.0168; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 48 Hour Postdose |
3.4733; 2.2156; 0.0193; NA; 0.0198; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 72 Hour Postdose |
3.8931; 3.0948; 0.0501; 0.0127; 0.0190; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 72 Hour Postdose |
3.3047; 1.9732; 0.0310; NA; 0.0256; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 96 Hour Postdose |
2.9148; 3.2956; 0.0136; 0.1420; 0.0120; 0.0593 | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 96 Hour Postdose |
2.4449; 2.2344; 0.0140; 0.0418; 0.0205; 0.0294 | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 144 Hour Postdose |
2.3326; 1.7990; 0.0297; NA; 0.0174; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 144 Hour Postdose |
2.0555; 1.2920; 0.0198; NA; 0.0140; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 336 Hour Postdose |
0.3130; 0.2723; NA; NA; NA; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 336 Hour Postdose |
0.4258; 0.2578; NA; NA; NA; NA | — |
| PRIMARY Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 480 Hour Postdose |
0.1189; 0.0941; NA; NA; NA; NA | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, Predose |
NA; 7.8900; NA; NA; NA; NA | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 0-24 Hours Postdose |
12.5668; 12.5020; 0.0878; 0.0521; 0.0883; 0.0254 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 24-48 Hours Postdose |
12.6225; 11.7995; 0.0690; 0.0392; 0.0863; 0.0277 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 48-72 Hours Postdose |
12.4089; 11.6600; 0.0812; 0.0419; 0.0867; 0.0322 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 72-96 Hours Postdose |
10.7766; 12.8426; 0.0867; 0.0427; 0.0882; 0.0394 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 96-120 Hours Postdose |
10.8018; 9.5626; 0.0885; 0.0414; 0.1053; 0.0406 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 120-144 Hours Postdose |
6.7161; 7.9830; 0.0730; 0.0335; 0.0836; 0.0301 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 144-168 Hours Postdose |
5.5693; 5.8025; 0.0579; 0.0448; 0.0747; 0.0287 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 336-360 Hours Postdose |
1.0727; 1.3326; 0.0459; NA; 0.0289; NA | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 1, 480-504 Hours Postdose |
0.4420; 0.3505; NA; NA; NA; NA | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, Predose |
0.3171; 0.4227; NA; NA; NA; NA | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 0-24 Hours Postdose |
10.7174; 12.4438; 0.0454; 0.0451; 0.0509; 0.0301 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 24-48 Hours Postdose |
11.1360; 13.2483; 0.0604; 0.0413; 0.0808; 0.0311 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 48-72 Hours Postdose |
12.7267; 13.8072; 0.0620; 0.0524; 0.0746; 0.0406 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 72-96 Hours Postdose |
11.2527; 12.2263; 0.0702; 0.0611; 0.0937; 0.0437 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 96-120 Hours Postdose |
8.3817; 8.1426; 0.0710; 0.0512; 0.0916; 0.0435 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 120-144 Hours Postdose |
7.3500; 7.5871; 0.0461; 0.0520; 0.0657; 0.0342 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 144-168 Hours Postdose |
6.1125; 4.6823; 0.0538; 0.0562; 0.0662; 0.0308 | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 336-360 Hours Postdose |
1.2811; 0.8271; 0.0377; NA; 0.0347; NA | — |
| PRIMARY Amount of Monomethylauristatin E (MMAE) and Its Metabolites Excreted in Urine at Cycle 3, 480-504 Hours Postdose |
0.4660; 0.3334; 0.0248; NA; 0.0377; NA | — |
| SECONDARY Serum Concentrations of Antibody-drug Conjugate (ADC) |
NA; NA; 29609.7759; 33125.0025; 24398.6482; 24533.2372 | — |
| SECONDARY Serum Concentration of Total Antibody (TAb) |
NA; NA; 30874.4957; 30884.9074; 28577.3869; 28865.4674 | — |
| SECONDARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
9; 9; 4; 0 | — |
| SECONDARY Number of Participants With Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin |
5; 7; 1; 0; 2; 2 | — |
| SECONDARY Number of Participants With Markedly Abnormal Laboratory Values |
5; 5 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
1; 2 | — |
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
Data sourced from ClinicalTrials.gov (NCT01950364). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.