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

Phase 1
Terminated
Conditions
Multiple Myeloma
Interventions
Biological: BI-505
Other: High dose melphalan
Other: Autologous stem cell transplantation
Registration Number
NCT02756728
Lead Sponsor
BioInvent International AB
Brief Summary

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

N/A study is closed

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
5
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:

    1. Serum M-spike ≥0.1 g/dl
    2. Urine M-spike >200 mg in a 24-hour urine collection
    3. 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
BI-505BI-505Biweekly infusions of BI-505 in addition to High dose Melphalan + Autologous Stem Cell Transplantation
HDM+ASCTHigh dose melphalanStandard of care; High dose Melphalan + Autologous Stem Cell Transplantation
BI-505High dose melphalanBiweekly infusions of BI-505 in addition to High dose Melphalan + Autologous Stem Cell Transplantation
HDM+ASCTAutologous stem cell transplantationStandard of care; High dose Melphalan + Autologous Stem Cell Transplantation
BI-505Autologous stem cell transplantationBiweekly infusions of BI-505 in addition to High dose Melphalan + Autologous Stem Cell Transplantation
Primary Outcome Measures
NameTimeMethod
Phase I: Determine the safety and feasibility of administering BI-505 in conjunction with HDM+ASCT in multiple myeloma patientsAdverse events will be assessed within 30 days of ASCT in the safety part of the study.

UNK

Phase II: Determine the effect of BI-505 on rate of stringent complete response for multiple myeloma patients with measurable disease pre-ASCT.At Day 100 after ASCT

UNK

Secondary Outcome Measures
NameTimeMethod
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).Day 100 after ASCT

UNK

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.At one year and up to three years after ASCT

UNK

Evaluate the effect of BI-505 on MRD-negative rate at day 100 and change in MRD status at day 100 compared to baseline.Day 100

UNK

Evaluate anti-myeloma effect of BI-505 monotherapy, prior to HDM + ASCTPrior to HDM + ASCT (from Day -17 until Day 0)

UNK

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-505Day 100 compared to Baseline (Day -17 and Day -2)

UNK

Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing CmaxAll 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

Maximum Plasma Concentration (Cmax)

Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing TmaxAll 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

Time to reach Cmax (Tmax)

Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing AUCAll 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

Area under the curve (AUC)

Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing CLAll 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

Clearance (CL)

Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing VssAll 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

Volume of distribution at steady state (Vss)

Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing t1/2All 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

Elimination half-life (t1/2)

Trial Locations

Locations (1)

Perelman School of Medicine/Hospital of the Univ. of Pennsylvania/Abramson Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

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