Clinical trial NCT02756728: A Phase I/II Study of BI-505 in Conjunction With Autologous Stem Cell Transplant in Multiple Myeloma
Official title: A Randomized Phase I/II Study of BI-505 in Conjunction With High-dose Melphalan and Autologous Stem Cell Transplantation for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: BioInvent International AB
Sponsor class: INDUSTRY
First posted: 2016-04-29
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Phase I: Determine the safety and feasibility of administering BI-505 in conjunction with HDM+ASCT in multiple myeloma patients
timeFrame: Adverse events will be assessed within 30 days of ASCT in the safety part of the study.
measure: Phase II: Determine the effect of BI-505 on rate of stringent complete response for multiple myeloma patients with measurable disease pre-ASCT.
timeFrame: At Day 100 after ASCT
Secondary outcomes:
measure: 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).
timeFrame: Day 100 after ASCT
measure: 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.
timeFrame: At one year and up to three years after ASCT
measure: Evaluate the effect of BI-505 on MRD-negative rate at day 100 and change in MRD status at day 100 compared to baseline.
timeFrame: Day 100
measure: Evaluate anti-myeloma effect of BI-505 monotherapy, prior to HDM + ASCT
timeFrame: Prior to HDM + ASCT (from Day -17 until Day 0)
measure: 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
timeFrame: Day 100 compared to Baseline (Day -17 and Day -2)
measure: Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing Cmax
timeFrame: 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
measure: Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing Tmax
timeFrame: 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
measure: Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing AUC
timeFrame: 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
measure: Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing CL
timeFrame: 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
measure: Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing Vss
timeFrame: 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
measure: Evaluate the pharmacokinetic profile of BI-505 in this clinical setting by analysing t1/2
timeFrame: 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
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Perelman School of Medicine/Hospital of the Univ. of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
Study officials:
affiliation: Div of Hema/Onc, Dept.of Med, Perelman Center Advanced Med, Philadelphia PA
name: Alfred Garfall, MD
role: PRINCIPAL_INVESTIGATOR
References: