A Phase I/II Study of BI-505 in Conjunction With Autologous Stem Cell Transplant in Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety and efficacy of administering BI-505 in conjunction with high dose melphalan and stem cell transplantation in multiple myeloma patients.

Detailed Description
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N/A study is closed

Official Title
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A Randomized Phase I/II Study of BI-505 in Conjunction With High-dose Melphalan and Autologous Stem Cell Transplantation for Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: BI-505
* Other: High dose melphalan
* Other: Autologous stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of multiple myeloma by 2014 IMWG criteria and have been recommended to undergo HDM + ASCT as a standard-of-care therapy for their multiple myeloma. Subjects must have adequate vital organ function and functional status for HDM + ASCT Subjects must have collected and cryopreserved ≥4x106 hematopoietic stem cells per kg of actual body weight that are suitable for use in autologous stem cell transplantation in the judgment of the investigator. At the time of enrollment, subjects must have had at least a partial response, as defined by IMWG criteria and in comparison to baseline/pre-treatment parameters, to an induction regimen containing lenalidomide and/or bortezomib. Subjects must have measurable disease according to one of the following criteria: Serum M-spike ≥0.1 g/dl Urine M-spike >200 mg in a 24-hour urine collection Involved serum free light chain above the upper limit of normal and a serum free light chain ratio outside the normal range. At the time of enrollment, subjects must be within 12 months of the first dose of initial/induction therapy, and the anticipated day of ASCT must be within 12 months of the first dose of initial/induction therapy Exclusion Criteria: Prior allogeneic or autologous hematopoietic stem cell transplant Current active infections, including HIV and hepatitis C and B Autoimmune disease requiring ongoing immunosuppressive therapy. History of atrial fibrillation or flutter, including paroxysmal atrial fibrillation or flutter. History of transient ischemic attack or stroke. At the time of enrollment, subjects must not have required multi-agent continuous-infusion cytotoxic chemotherapy (e.g., regimens such as D-PACE) as part of their initial/induction therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HDM+ASCT<br>Standard of care; High dose Melphalan + Autologous Stem Cell Transplantation | Other: High dose melphalan<br>* High dose melphalan (HDM)<br>Other: Autologous stem cell transplantation<br>* Autologous stem cell transplantation (ASCT)<br>|
| Experimental: BI-505<br>Biweekly infusions of BI-505 in addition to High dose Melphalan + Autologous Stem Cell Transplantation | Biological: BI-505<br>* Treatment with BI-505 10 mg/kg bi-weekly infusion, up to 9 doses over 4 months<br>Other: High dose melphalan<br>* High dose melphalan (HDM)<br>Other: Autologous stem cell transplantation<br>* Autologous stem cell transplantation (ASCT)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Determine the safety and feasibility of administering BI-505 in conjunction with HDM+ASCT in multiple myeloma patients | UNK | Adverse events will be assessed within 30 days of ASCT in the safety part of the study. | 
| Phase II: Determine the effect of BI-505 on rate of stringent complete response for multiple myeloma patients with measurable disease pre-ASCT. | UNK | At Day 100 after ASCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the effect of BI-505 on rate of stringent complete response (sCR) at day 100 in subgroups stratified according to response to initial therapy (+/- VGPR). | UNK | Day 100 after ASCT | 
| Determine the effect of BI-505 administered in conjunction with HDM + ASCT on IMWG response category (PR, VGPR, CR, sCR) at one year post-ASCT and progression-free survival. | UNK | At one year and up to three years after ASCT | 
| Evaluate the effect of BI-505 on MRD-negative rate at day 100 and change in MRD status at day 100 compared to baseline. | UNK | Day 100 | 
| Evaluate anti-myeloma effect of BI-505 monotherapy, prior to HDM + ASCT | UNK | Prior to HDM + ASCT (from Day -17 until Day 0) | 
| Evaluate bone marrow immune cell composition and phenotype, including macrophage infiltration and expression of intracellular adhesion molecule (ICAM)-1 expression on multiple myeloma plasma cells, as potential biomarkers of response to BI-505 | UNK | Day 100 compared to Baseline (Day -17 and Day -2) | 
| Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing Cmax | Maximum Plasma Concentration (Cmax) | All dosing visits throughout the study (up to 9 biweekly infusions of BI-505). Day -17, day -3, day 11, day 25, day 39, day 53, day 67, day 81, day 95, day 123 | 
| Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing Tmax | Time to reach Cmax (Tmax) | All dosing visits throughout the study (up to 9 biweekly infusions of BI-505). Day -17, day -3, day 11, day 25, day 39, day 53, day 67, day 81, day 95, day 123 | 
| Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing AUC | Area under the curve (AUC) | All dosing visits throughout the study (up to 9 biweekly infusions of BI-505). Day -17, day -3, day 11, day 25, day 39, day 53, day 67, day 81, day 95, day 123 | 
| Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing CL | Clearance (CL) | All dosing visits throughout the study (up to 9 biweekly infusions of BI-505). Day -17, day -3, day 11, day 25, day 39, day 53, day 67, day 81, day 95, day 123 | 
| Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing Vss | Volume of distribution at steady state (Vss) | All dosing visits throughout the study (up to 9 biweekly infusions of BI-505). Day -17, day -3, day 11, day 25, day 39, day 53, day 67, day 81, day 95, day 123 | 
| Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing t1/2 | Elimination half-life (t1/2) | All dosing visits throughout the study (up to 9 biweekly infusions of BI-505). Day -17, day -3, day 11, day 25, day 39, day 53, day 67, day 81, day 95, day 123 |