A Study of OPD5 Followed by Autologous Stem Cell Transplant for Patients With Relapsed Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

— COAST  

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04918511
• Other study ID #: OP-501
• Status: Withdrawn
• Phase: Phase 1
• Start date: May 27, 2021
• Est. completion date: December 2025

Study information

• Verified date: November 2021
• Source: Oncopeptides AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2025
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapse Multiple Myeloma

Intervention

Drug:
• OPD5
OPD5 solution for i.v. infusion

Locations

Country	Name	City	State
Czechia	University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology	Brno
Czechia	University Hospital Ostrava, Clinic of Hematooncology	Ostrava
Czechia	Charles University and General Hospital in Prague, 1st Department of Medicine - Department of Hematology, First Faculty of Medicine	Praha

Sponsors (1)

Lead Sponsor	Collaborator
Oncopeptides AB

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and grade of Treatment Emergent Adverse Events (TEAEs)	Including frequency and grade of defined Dose Limiting Toxicities	30 days post OPD5 treatment with ASCT
Primary	Incidence of clinically significant changes in clinical laboratory parameters		30 days post OPD5 treatment with ASCT
Primary	Magnitude of clinically significant changes in clinical laboratory parameters		30 days post OPD5 treatment with ASCT
Primary	Incidence of clinically significant adverse findings in vital signs		30 days post OPD5 treatment with ASCT
Primary	Severity of clinically significant adverse findings in vital signs		30 days post OPD5 treatment with ASCT
Primary	Incidence of clinically significant adverse findings in electrocardiograms (ECGs)		30 days post OPD5 treatment with ASCT
Primary	Severity of clinically significant adverse findings in electrocardiograms (ECGs)		30 days post OPD5 treatment with ASCT
Primary	Incidence of clinically significant adverse findings in other physical examination parameters		30 days post OPD5 treatment with ASCT
Primary	Severity of clinically significant adverse findings in other physical examination parameters		30 days post OPD5 treatment with ASCT
Primary	Incidence of mucositis		30 days post OPD5 treatment with ASCT
Primary	Severity of mucositis	Using World Health Organization (WHO) oral toxicity scale, from 0 (no change) to 4 (oral feeding is not possible)	30 days post OPD5 treatment with ASCT
Primary	The number of deaths not related to relapse or progression		100 days post OPD5 treatment with ASCT
Secondary	Best Response	Best response for a single patient. Best response will include the following categories: stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) and Progressive Disease (PD) as assessed by the investigator according to International Myeloma Working Group Uniform Response Criteria (IMWG-URC)	30 days post OPD5 treatment with ASCT
Secondary	Overall Response Rate (ORR)	Proportion of patients who achieve response of CR, sCR, VGPR or PR as their best response.	approximately 100 days post OPD5 treatment with ASCT
Secondary	Duration of response (DOR)	Time from the first confirmed response of sCR, CR, VGPR or PR to first confirmed disease progression, or death due to any cause	approximately 12 months
Secondary	Time to progression (TTP)	Time from the date of OPD5 administration to the date of the first documented confirmed PD	approximately 12 months
Secondary	Time to next treatment (TTNT)	Time from the date of OPD5 administration start to the start of first post study myeloma therapy (maintenance MM treatment not considered as new line of therapy)	approximately 12 months
Secondary	Progression Free Survival (PFS)	Time from the date of OPD5 dosing to the date of first documentation of confirmed progressive disease (PD) or death due to any cause	approximately 12 months
Secondary	Pharmacokinetics Area under the curve AUC(0-t) for OPD5 and the metabolites desethyl-melflufen and melphalan		Day -1 (the day of OPD5 infusion)
Secondary	Pharmacokinetics AUC(0-infinity) for OPD5 and the metabolites desethyl-melflufen and melphalan		Day -1 (the day of OPD5 infusion)
Secondary	Pharmacokinetics elimination half-life (t½) for OPD5 and the metabolites desethyl-melflufen and melphalan		Day -1 (the day of OPD5 infusion)
Secondary	Pharmacokinetics Cmax for OPD5 and the metabolites desethyl-melflufen and melphalan		Day -1 (the day of OPD5 infusion)
Secondary	Time to hematological recovery	defined as the return of Absolute Neutrophil Count (ANC) = 0.5 x 10^9/L and platelets = 20 x 10^9/L for two consecutive days	approximately Day 14
Secondary	Time to myeloablation	defined as the first of at least two consecutive days with ANC < 0.5 x 10^9/L and platelets <20 x 10^9/L	approximately Day 14
Secondary	Minimal Residual Disease (MRD) status by Next Generation sequencing (NGS) in patients that achieve a CR or VGPR.		approximately Day 100