NCT04918511 - A Study of OPD5 Followed by Autologous Stem Cell Transplant for Patients With Relapsed Refractory Multiple Myeloma | Crick | Crick

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

Phase 1WithdrawnNCT04918511

Oncopeptides AB

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

Relapse Multiple Myeloma Multiple Myeloma

Interventions

OPD5DRUG

OPD5 solution for i.v. infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

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

Prague, Czechia

Outcomes

Primary Outcomes

Incidence and grade of Treatment Emergent Adverse Events (TEAEs)

Including frequency and grade of defined Dose Limiting Toxicities

Time frame: 30 days post OPD5 treatment with ASCT

Incidence of clinically significant changes in clinical laboratory parameters

Time frame: 30 days post OPD5 treatment with ASCT

Magnitude of clinically significant changes in clinical laboratory parameters

Time frame: 30 days post OPD5 treatment with ASCT

Incidence of clinically significant adverse findings in vital signs

Time frame: 30 days post OPD5 treatment with ASCT

Severity of clinically significant adverse findings in vital signs

Time frame: 30 days post OPD5 treatment with ASCT

Incidence of clinically significant adverse findings in electrocardiograms (ECGs)

Time frame: 30 days post OPD5 treatment with ASCT

Severity of clinically significant adverse findings in electrocardiograms (ECGs)

Time frame: 30 days post OPD5 treatment with ASCT

Incidence of clinically significant adverse findings in other physical examination parameters

Time frame: 30 days post OPD5 treatment with ASCT

Severity of clinically significant adverse findings in other physical examination parameters

Time frame: 30 days post OPD5 treatment with ASCT

Incidence of mucositis

Time frame: 30 days post OPD5 treatment with ASCT

Data from ClinicalTrials.gov

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Secondary Outcomes

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)

Time frame: 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.

Time frame: 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

Time frame: approximately 12 months

Time to progression (TTP)

Time from the date of OPD5 administration to the date of the first documented confirmed PD

Time frame: 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)

Time frame: 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

Time frame: approximately 12 months

Pharmacokinetics Area under the curve AUC(0-t) for OPD5 and the metabolites desethyl-melflufen and melphalan

Time frame: Day -1 (the day of OPD5 infusion)

Pharmacokinetics AUC(0-infinity) for OPD5 and the metabolites desethyl-melflufen and melphalan

Time frame: Day -1 (the day of OPD5 infusion)

Pharmacokinetics elimination half-life (t½) for OPD5 and the metabolites desethyl-melflufen and melphalan

Time frame: Day -1 (the day of OPD5 infusion)

Pharmacokinetics Cmax for OPD5 and the metabolites desethyl-melflufen and melphalan

Time frame: 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

Time frame: 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

Time frame: approximately Day 14

Minimal Residual Disease (MRD) status by Next Generation sequencing (NGS) in patients that achieve a CR or VGPR.

Time frame: approximately Day 100