Nivolumab Role in the Treatment of Patients With Refractory or Relapse Multiple Myeloma

Multiple Myeloma Clinical Trial

Status Terminated

Clinical Trial Summary

This is an open-label, non-randomized Phase 1 study evaluating the role of two regimens:

A) Nivolumab in combination with Pomalidomide and low dose dexamethasone and B) Nivolumab + Elotuzumab + Pomalidomide + dexamethasone in the treatment of relapse or refractory multiple myeloma patients.

The study will be performed in 10 sites in Spain. First, the MTD for the Nivo-Pom-Dex combination will be determined using a 3+3 scheme. Once the MTD has been determined both Regimes (A and B) will be open for full accrual and patients will be included in an alternating way in both regimes simultaneously. In the case that an unacceptable toxicity was seen in the Lead-in phase (Nivolumab + Pomalidomide + low dose dexamethasone), the other phase would not be open.

A safety analysis by an internal review committee will be performed once the first six patients included in the regimen B have completed the first two cycles.

The main purpose of the study is to analyze the proportion of subjects, with refractory or relapsed multiple myeloma, receiving the combination Nivo-Pom-dex or Nivo-Pom-dex-Elo experience one or more haematological and non haematological SAE (grade 3 or higher).

Additionally, other

Research Hypothesis:

The combination of nivolumab with pomalidomide and dexamethasone will demonstrate adequate safety and tolerability to permit further testing of these combinations in subjects with multiple myeloma. The addition of elotuzumab to nivolumab, pomalidomide and dexamethasone will not change the safety profile.

Duration of Study:

The study will remain open for enrolment for 15 months (estimated), or until the planned total number of 40 subjects is reached if this happens first.

The follow-up of the last recruited patient will be up to 3 years, being the Final analyses performed 1,5 years after the last patient is included.

Study Population:

Male and female adult patients with Multiple Myeloma in first or subsequent relapses, previously exposed to both a proteasome inhibitor and a IMID (Lenalidomide). Patients may be exposed, relapsed or refractory to Lenalidomide.

Clinical Trial Description

Test Product, Dose and Mode of Administration, Duration of Treatment:

The study is using a modified 3+3 design and has 2 parts. First (Lead-In phase), the MTD for the Nivo-Pom-dex combination will be determined:

Regimen A: The treatment regimen will include Pomalidomide, Nivolumab and low dose dexamethasone. There will be three different dose levels:

• First dose level (DL1): Nivolumab 240mg intravenous infusion, every other week; Pomalidomide at the standard dose of 4 mg/day from day 1 to 21 in a 28-day cycle and Dexamethasone 40mg weekly except for patients older than 75 or with comorbidities who will received 20 mg weekly.

Initially, 3 patients will be enrolled and treated. If not DLT, 3 additional patients will be included at the same dose level.

• In the case there is DLT, the dose level will be de-escalated.

• If the DLT is haematological or non-hematological attributable to Pomalidomide, the dose level will be DL-1P (Pomalidomide 2 mg/d from day 1-21, Nivolumab 240mg every other week and Dexamethasone 40mg weekly or 20 weekly in patients older than 75 or with comorbidities.

• In the case the DLT is non-hematological, and attributable to Nivolumab, this combination arm will be stopped. No Nivolumab dose reductions are allowed in the trial.

Once the MTD has been determined, both regimens A and B will be open for full accrual and patients will be included in an alternating way in both regimens simultaneously.

Regimen B: The treatment regimen will include Pomalidomide and Nivolumab at the selected dose level from the previous arm of the study. Dexamethasone will be given in the standard dose of 40mg weekly on days 1, 8, 15 and 22 of each 28-day cycle and could be reduced to 20mg weekly in case of age above 75 year-old or comorbidities. Elotuzumab will be given at the standard dose of 10mg/kg weekly for the first two cycles, and then on days 1 and 15 for the subsequent cycles.

Treatment will be maintained until disease progression.

Criteria for Evaluation:

• Safety: Adverse events will be assessed continuously during the study and for 100 days after the last treatment. Adverse events will be coded using the most current version of MedDRA and reviewed for potential significance and importance. Adverse events will be evaluated according to the NCI CTCAE Version 4.0. Subjects should be followed until all treatment related adverse events have recovered to grade ≤ 1 or baseline, or are deemed irreversible by the investigator. Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests.

• Efficacy: Disease assessment will be performed with serum and urine myeloma lab tests, bone marrow assessment and computed tomography (CT) and/or magnetic resonance imaging (MRI), as appropriate. Myeloma responses will be based on investigator assessment and determined as defined by IMWG criteria. Any initial assessment will be confirmed by a repeat evaluation every 4 weeks.

• Biomarker Assessments: Peripheral blood and bone marrow samples will be collected from subjects to assess mechanisms of primary resistance (cell surface protein analyses and transcriptome analyses) and mechanisms of chemosensitivity to NivoPomDex combination (10-colour flow cytometry, TCR clonality by NGS). ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

• NCT number: NCT03023527
• Study type: Interventional
• Source: PETHEMA Foundation
• Status: Terminated
• Phase: Phase 1
• Start date: January 2017
• Completion date: January 2018