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Sponsor made the decision to terminate the COAST study to refocus the OPD5 clinical program.
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose cohort 1 | Experimental | In dose cohort 1, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level of 30 mg/m2 (dose based on body surface area) |
|
| Dose cohort 2 | Experimental | In dose cohort 2, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 1 |
|
| Dose cohort 3 | Experimental | In dose cohort 3, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 2 |
|
| Dose cohort 4 | Experimental | In dose cohort 4, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 3 |
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| Dose cohort 5 | Experimental | In dose cohort 5, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 4 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| OPD5 | Drug | OPD5 solution for i.v. infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Incidence of clinically significant changes in clinical laboratory parameters | 30 days post OPD5 treatment with ASCT | |
| Magnitude of clinically significant changes in clinical laboratory parameters | 30 days post OPD5 treatment with ASCT | |
| Incidence of clinically significant adverse findings in vital signs | 30 days post OPD5 treatment with ASCT | |
| Severity of clinically significant adverse findings in vital signs | 30 days post OPD5 treatment with ASCT | |
| Incidence of clinically significant adverse findings in electrocardiograms (ECGs) | 30 days post OPD5 treatment with ASCT | |
| Severity of clinically significant adverse findings in electrocardiograms (ECGs) | 30 days post OPD5 treatment with ASCT | |
| Incidence of clinically significant adverse findings in other physical examination parameters | 30 days post OPD5 treatment with ASCT | |
| Severity of clinically significant adverse findings in other physical examination parameters |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sergio Giralt, MD | Memorial Sloan Kettering Cancer Centre, New York City, United States | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology | Brno | 62500 | Czechia | |||
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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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.
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| Dose cohort 6 | Experimental | In dose cohort 6, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 5 |
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| Dose cohort 7 | Experimental | In dose cohort 7, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 6 |
|
| 30 days post OPD5 treatment with ASCT |
| Incidence of mucositis | 30 days post OPD5 treatment with ASCT |
| 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 |
| The number of deaths not related to relapse or progression | 100 days post OPD5 treatment with ASCT |
| 30 days post OPD5 treatment with ASCT |
| 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 |
| 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 |
| Time to progression (TTP) | Time from the date of OPD5 administration to the date of the first documented confirmed PD | approximately 12 months |
| 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 |
| 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 |
| Pharmacokinetics Area under the curve AUC(0-t) for OPD5 and the metabolites desethyl-melflufen and melphalan | Day -1 (the day of OPD5 infusion) |
| Pharmacokinetics AUC(0-infinity) for OPD5 and the metabolites desethyl-melflufen and melphalan | Day -1 (the day of OPD5 infusion) |
| Pharmacokinetics elimination half-life (t½) for OPD5 and the metabolites desethyl-melflufen and melphalan | Day -1 (the day of OPD5 infusion) |
| Pharmacokinetics Cmax for OPD5 and the metabolites desethyl-melflufen and melphalan | Day -1 (the day of OPD5 infusion) |
| 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 |
| 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 |
| Minimal Residual Disease (MRD) status by Next Generation sequencing (NGS) in patients that achieve a CR or VGPR. | approximately Day 100 |
| 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 | Prague | Czechia |
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |