Clinical trial NCT04918511: A Study of OPD5 Followed by Autologous Stem Cell Transplant for Patients With Relapsed Refractory Multiple Myeloma
Official title: An Open-label Phase I, Dose Escalation Study of the Safety and Tolerability of OPD5 as Myeloablative Conditioning Regimen Followed by Autologous Stem Cell Transplant (ASCT) for Patients With Relapsed Refractory Multiple Myeloma (RRMM)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Relapse Multiple Myeloma
Multiple Myeloma
Lead sponsor: Oncopeptides AB
Sponsor class: INDUSTRY
First posted: 2021-06-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: A minimum of 3 and up to 6 evaluable patients will be enrolled per dose level. After the first cohort, the doses for the following dose cohorts will be adaptively escalated/de-escalated based on observed dose limiting toxicities in previous cohort.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of a single infusion of OPD5 before Autologous Stem Cell Transplant in patients with RRMM. The study will evaluate increasing doses of OPD5 to find the best dose and to assess any side effects. Each patient will be assigned to a dose cohort of 3-6 patients to receive one single dose of OPD5. Each patient will be hospitalized for about 14 days from the OPD5 infusion and then have monthly visits to the clinic for 3 months and then every third month until disease progression or starting new myeloma treatment, maximum up to 2 years.


Eligibility criteria: Inclusion Criteria:

* Male or female, between the ages of 18 years and 70 years at the planned time of study treatment; patients greater than 70 years of age may qualify on a case by case basis
* Diagnosis of multiple myeloma
* Received a previous Autologous Stem Cell Transplantation ( ASCT) (single or tandem) that resulted in disease progression within 24 months
* Received at least 2 prior lines of therapy
* Refractory to previous treatment with a Proteasome Inhibitor (PI), an immunomodulatory drug (IMiD) and an anti-Cluster of Differentiation 38 monoclonal antibody (anti-CD38 mAb)
* Male and women of childbearing potential agrees to use contraception during the treatment period and during a specified time period after the last dose

Exclusion Criteria:

* Prior treatment with melphalan flufenamide (melflufen) or OPD5
* Any medical condition that may interfere with safety or participation in this study
* Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance
* Prior allogeneic stem cell transplantation or prior salvage ASCT

Primary outcomes:
measure: Incidence and grade of Treatment Emergent Adverse Events (TEAEs)
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Incidence of clinically significant changes in clinical laboratory parameters
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Magnitude of clinically significant changes in clinical laboratory parameters
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Incidence of clinically significant adverse findings in vital signs
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Severity of clinically significant adverse findings in vital signs
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Incidence of clinically significant adverse findings in electrocardiograms (ECGs)
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Severity of clinically significant adverse findings in electrocardiograms (ECGs)
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Incidence of clinically significant adverse findings in other physical examination parameters
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Severity of clinically significant adverse findings in other physical examination parameters
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Incidence of mucositis
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Severity of mucositis
timeFrame: 30 days post OPD5 treatment with ASCT
measure: The number of deaths not related to relapse or progression
timeFrame: 100 days post OPD5 treatment with ASCT
Secondary outcomes:
measure: Best Response
timeFrame: 30 days post OPD5 treatment with ASCT
measure: Overall Response Rate (ORR)
timeFrame: approximately 100 days post OPD5 treatment with ASCT
measure: Duration of response (DOR)
timeFrame: approximately 12 months
measure: Time to progression (TTP)
timeFrame: approximately 12 months
measure: Time to next treatment (TTNT)
timeFrame: approximately 12 months
measure: Progression Free Survival (PFS)
timeFrame: approximately 12 months
measure: Pharmacokinetics Area under the curve AUC(0-t) for OPD5 and the metabolites desethyl-melflufen and melphalan
timeFrame: Day -1 (the day of OPD5 infusion)
measure: Pharmacokinetics AUC(0-infinity) for OPD5 and the metabolites desethyl-melflufen and melphalan
timeFrame: Day -1 (the day of OPD5 infusion)
measure: Pharmacokinetics elimination half-life (t½) for OPD5 and the metabolites desethyl-melflufen and melphalan
timeFrame: Day -1 (the day of OPD5 infusion)
measure: Pharmacokinetics Cmax for OPD5 and the metabolites desethyl-melflufen and melphalan
timeFrame: Day -1 (the day of OPD5 infusion)
measure: Time to hematological recovery
timeFrame: approximately Day 14
measure: Time to myeloablation
timeFrame: approximately Day 14
measure: Minimal Residual Disease (MRD) status by Next Generation sequencing (NGS) in patients that achieve a CR or VGPR.
timeFrame: approximately Day 100
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
city: Ostrava
country: Czechia
facility: University Hospital Ostrava, Clinic of Hematooncology
city: Praha
country: Czechia
facility: Charles University and General Hospital in Prague, 1st Department of Medicine - Department of Hematology, First Faculty of Medicine
Study officials:
affiliation: Memorial Sloan Kettering Cancer Centre, New York City, United States
name: Sergio Giralt, MD
role: PRINCIPAL_INVESTIGATOR
References: