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

Primary Purpose

Relapse Multiple Myeloma, Multiple Myeloma

Status
Withdrawn
Phase
Phase 1
Locations
Czechia
Study Type
Interventional
Intervention
OPD5
Sponsored by
Oncopeptides AB
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapse Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
  • University Hospital Ostrava, Clinic of Hematooncology
  • Charles University and General Hospital in Prague, 1st Department of Medicine - Department of Hematology, First Faculty of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose cohort 1

Dose cohort 2

Dose cohort 3

Dose cohort 4

Dose cohort 5

Dose cohort 6

Dose cohort 7

Arm Description

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)

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

Incidence and grade of Treatment Emergent Adverse Events (TEAEs)
Including frequency and grade of defined Dose Limiting Toxicities
Incidence of clinically significant changes in clinical laboratory parameters
Magnitude of clinically significant changes in clinical laboratory parameters
Incidence of clinically significant adverse findings in vital signs
Severity of clinically significant adverse findings in vital signs
Incidence of clinically significant adverse findings in electrocardiograms (ECGs)
Severity of clinically significant adverse findings in electrocardiograms (ECGs)
Incidence of clinically significant adverse findings in other physical examination parameters
Severity of clinically significant adverse findings in other physical examination parameters
Incidence of mucositis
Severity of mucositis
Using World Health Organization (WHO) oral toxicity scale, from 0 (no change) to 4 (oral feeding is not possible)
The number of deaths not related to relapse or progression

Secondary Outcome Measures

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)
Overall Response Rate (ORR)
Proportion of patients who achieve response of CR, sCR, VGPR or PR as their best response.
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 to progression (TTP)
Time from the date of OPD5 administration to the date of the first documented confirmed PD
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)
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
Pharmacokinetics Area under the curve AUC(0-t) for OPD5 and the metabolites desethyl-melflufen and melphalan
Pharmacokinetics AUC(0-infinity) for OPD5 and the metabolites desethyl-melflufen and melphalan
Pharmacokinetics elimination half-life (t½) for OPD5 and the metabolites desethyl-melflufen and melphalan
Pharmacokinetics Cmax for OPD5 and the metabolites desethyl-melflufen and melphalan
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 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
Minimal Residual Disease (MRD) status by Next Generation sequencing (NGS) in patients that achieve a CR or VGPR.

Full Information

First Posted
May 27, 2021
Last Updated
November 17, 2021
Sponsor
Oncopeptides AB
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1. Study Identification

Unique Protocol Identification Number
NCT04918511
Brief Title
A Study of OPD5 Followed by Autologous Stem Cell Transplant for Patients With Relapsed Refractory Multiple Myeloma
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Sponsor made the decision to terminate the COAST study to refocus the OPD5 clinical program.
Study Start Date
May 27, 2021 (Anticipated)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oncopeptides AB

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapse Multiple Myeloma, Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose cohort 1
Arm Type
Experimental
Arm Description
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)
Arm Title
Dose cohort 2
Arm Type
Experimental
Arm Description
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
Arm Title
Dose cohort 3
Arm Type
Experimental
Arm Description
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
Arm Title
Dose cohort 4
Arm Type
Experimental
Arm Description
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
Arm Title
Dose cohort 5
Arm Type
Experimental
Arm Description
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
Arm Title
Dose cohort 6
Arm Type
Experimental
Arm Description
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
Arm Title
Dose cohort 7
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
OPD5
Intervention Description
OPD5 solution for i.v. infusion
Primary Outcome Measure Information:
Title
Incidence and grade of Treatment Emergent Adverse Events (TEAEs)
Description
Including frequency and grade of defined Dose Limiting Toxicities
Time Frame
30 days post OPD5 treatment with ASCT
Title
Incidence of clinically significant changes in clinical laboratory parameters
Time Frame
30 days post OPD5 treatment with ASCT
Title
Magnitude of clinically significant changes in clinical laboratory parameters
Time Frame
30 days post OPD5 treatment with ASCT
Title
Incidence of clinically significant adverse findings in vital signs
Time Frame
30 days post OPD5 treatment with ASCT
Title
Severity of clinically significant adverse findings in vital signs
Time Frame
30 days post OPD5 treatment with ASCT
Title
Incidence of clinically significant adverse findings in electrocardiograms (ECGs)
Time Frame
30 days post OPD5 treatment with ASCT
Title
Severity of clinically significant adverse findings in electrocardiograms (ECGs)
Time Frame
30 days post OPD5 treatment with ASCT
Title
Incidence of clinically significant adverse findings in other physical examination parameters
Time Frame
30 days post OPD5 treatment with ASCT
Title
Severity of clinically significant adverse findings in other physical examination parameters
Time Frame
30 days post OPD5 treatment with ASCT
Title
Incidence of mucositis
Time Frame
30 days post OPD5 treatment with ASCT
Title
Severity of mucositis
Description
Using World Health Organization (WHO) oral toxicity scale, from 0 (no change) to 4 (oral feeding is not possible)
Time Frame
30 days post OPD5 treatment with ASCT
Title
The number of deaths not related to relapse or progression
Time Frame
100 days post OPD5 treatment with ASCT
Secondary Outcome Measure Information:
Title
Best Response
Description
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
Title
Overall Response Rate (ORR)
Description
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
Title
Duration of response (DOR)
Description
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
Title
Time to progression (TTP)
Description
Time from the date of OPD5 administration to the date of the first documented confirmed PD
Time Frame
approximately 12 months
Title
Time to next treatment (TTNT)
Description
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
Title
Progression Free Survival (PFS)
Description
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
Title
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)
Title
Pharmacokinetics AUC(0-infinity) for OPD5 and the metabolites desethyl-melflufen and melphalan
Time Frame
Day -1 (the day of OPD5 infusion)
Title
Pharmacokinetics elimination half-life (t½) for OPD5 and the metabolites desethyl-melflufen and melphalan
Time Frame
Day -1 (the day of OPD5 infusion)
Title
Pharmacokinetics Cmax for OPD5 and the metabolites desethyl-melflufen and melphalan
Time Frame
Day -1 (the day of OPD5 infusion)
Title
Time to hematological recovery
Description
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
Title
Time to myeloablation
Description
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
Title
Minimal Residual Disease (MRD) status by Next Generation sequencing (NGS) in patients that achieve a CR or VGPR.
Time Frame
approximately Day 100

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sergio Giralt, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Centre, New York City, United States
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
City
Brno
ZIP/Postal Code
62500
Country
Czechia
Facility Name
University Hospital Ostrava, Clinic of Hematooncology
City
Ostrava
Country
Czechia
Facility Name
Charles University and General Hospital in Prague, 1st Department of Medicine - Department of Hematology, First Faculty of Medicine
City
Praha
Country
Czechia

12. IPD Sharing Statement

Learn more about this trial

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

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