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

Hodgkin Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01950364
• Other study ID #: C25005
• Secondary ID: 2013-000193-29WH
• Status: Completed
• Phase: Phase 1
• First received: September 23, 2013
• Last updated: January 6, 2016
• Start date: November 2013
• Est. completion date: October 2014

Study information

• Verified date: January 2016
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

This is an open-label trial to estimate the concentrations of brentuximab vedotin in relapsed/refractory HL or relapsed/refractory sALCL patients treated with either brentuximab vedotin or brentuximab vedotin + rifampicin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or female patients 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 patients 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 patients 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:

• Patients for whom rifampicin is contraindicated

• Previously received an allogeneic transplant.

• Patients with current diagnosis of primary cutaneous ALCL (patients whose ALCL has transformed to sALCL are eligible).

• Known cerebral/meningeal disease including signs or symptoms of progressive multifocal leukoencephalopathy (PML)

• Female patients 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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anaplastic Large-cell Lymphoma
• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Non-Hodgkin

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Belgium,  Lithuania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 1: Predose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 1: 0-24 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 1: 24-48 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 1: 48-72 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 1: 72-96 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 1: 96-120 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 1: 120-144 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 1: 144-168 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 1: 336-360 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 1: 480-504 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 3: Predose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 3: 0-24 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 3: 24-48 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 3: 48-72 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 3: 72-96 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 3: 96-120 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 3: 120-144 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 3: 144-168 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 3: 336-360 hours postdose	No
Primary	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. The LLQ for all the observations was 0.01 ng/mL.	Cycle 3: 480-504 hours postdose	No
Secondary	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	No
Secondary	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	No
Secondary	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.	Baseline up to 30 days after last dose of study drug (30 days after Cycle 16)	Yes
Secondary	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.	Day 1 of Cycle 1 and 3	Yes
Secondary	Number of Participants With Markedly Abnormal Laboratory Values	The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.	Baseline up to 30 days after last dose of study drug (30 Days after Cycle 8)	Yes
Secondary	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Vital signs included body temperature, body weight, blood pressure and heart rate.	Baseline up to 30 days after last dose of study drug (30 Days after Cycle 8)	Yes