Phase Ib of Cyclophosphamide, Pomalidomide, Dexamethasone and Daratumumab (CPD-DARA) in patients with relapsed/refractory multiple myeloma. (The CPD-DARA Study).

Phase 1

Active, not recruiting

• Conditions: Relapsed/ refractory multiple myeloma
• Interventions: Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Pomalidomide; Drug: Dexamethasone

• Registration Number: 2024-516945-37-00
• Lead Sponsor: Cancer Trials Ireland

Brief Summary

This study is a Phase Ib, open label, single arm, adaptive multi-centre clinical study. The target population for this study are patients with relapsed/refractory multiple myeloma (MM). Patients will have a confirmed diagnosis of MM, with measurable disease as per IMWG criteria, in the second relapse and beyond (third line of therapy and beyond). Patients will need to have exposure to lenalidomide and a proteasome inhibitor. Patients will be treated with Cyclophosphamide-Pomalidomide-Dexamethasone (CPD) in combination with daratumumab (DARA) to determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D) of the combination.

Pomalidomide will be administered orally at three dose levels 4, 3 and 2mg on days 1-21 of each 28-day cycle. Treatment will be repeated on day 1 of a 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, physician's decision, or sponsor's decision to terminate the study, whichever occurs first.

Detailed Description

Primary Objective 1. To determine the MTD and RP2D for pomalidomide that can safely be administered with DARA and cyclophosphamide.

Primary Endpoint

1. To determine the incidence of DLT within the first cycle of CPD in combination with DARA at each dose level.

Secondary Objectives

1. To evaluate the safety and tolerability of the CPD-DARA regimen.

2. To evaluate efficacy measures. Secondary Endpoints

1. Safety will be assessed by standard clinical and laboratory tests (haematology, serum chemistry). Adverse events grade will be defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 5.0.

2. The following efficacy endpoints will be measured: i. Complete Response (CR) rate after six cycles of CPD-DARA and at the end of study treatment.

ii. Best Overall Response. iii. Minimal Residual Disease (MRD) negative rate after six cycles of CPD-DARA. iv. Progression Free Survival (PFS) and Overall Survival (OS) at 6 months and 2 years.

v. Time to Response. Exploratory Objectives

1. To assess effect of CPD-DARA treatment on patient-reported outcomes and quality of life.

2. Efficacy according to the IMWG (International Myeloma Working Group) in High Risk vs Standard Risk patients.

3. Disease Control Rate (DCR). Exploratory Endpoints

1. To assess effect of CPD-DARA treatment on patient-reported outcomes and quality of life, as assessed by the FACT-G and MyPOS questionnaires completed at study commencement, at every cycle of study treatment and at completion of the study treatment.

2. Efficacy according to the IMWG in High Risk (defined by ISS stage 3 and/or high-risk cytogenetic findings including t(4;14), t(14;16), and del17p) vs Standard Risk patients.

3. Disease Control Rate (DCR) defined as stable disease or better.

Study Timeline

• Study First Posted: 2024-10-29
• Last Update Posted: 2024-10-29

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CPD-DARA	Pomalidomide	Drug: Daratumumab Other Name: Darzalex Drug: Cyclophosphamide Drug: Pomalidomide Other Name: Pomalyst/ Imnovid Drug: Dexamethasone
CPD-DARA	Daratumumab	Drug: Daratumumab Other Name: Darzalex Drug: Cyclophosphamide Drug: Pomalidomide Other Name: Pomalyst/ Imnovid Drug: Dexamethasone
CPD-DARA	Cyclophosphamide	Drug: Daratumumab Other Name: Darzalex Drug: Cyclophosphamide Drug: Pomalidomide Other Name: Pomalyst/ Imnovid Drug: Dexamethasone
CPD-DARA	Dexamethasone	Drug: Daratumumab Other Name: Darzalex Drug: Cyclophosphamide Drug: Pomalidomide Other Name: Pomalyst/ Imnovid Drug: Dexamethasone

Primary Outcome Measures

Name	Time	Method
Incidence of DLT within the first cycle of CPD in combination with DARA at each dose level.	Up to cycle 1

Secondary Outcome Measures

Name	Time	Method
MTD for pomalidomide that can safely be administered with DARA and cyclophosphamide.	Through study treatment, an average of 1 months

Trial Locations

Locations (3)

University Hospital Galway; 🇮🇪 Galway, Ireland

Cork University Hospital; 🇮🇪 Cork, Ireland

Beaumont Hospital; 🇮🇪 Dublin 9, Ireland

University Hospital Galway

🇮🇪Galway, Ireland

Janusz Krawczyk

Site contact

+35391544281

janusz.krawczyk@hse.ie