CPD-DARA in Patients With Relapsed/Refractory Multiple Myeloma.

NCT04667663 | Active Not Recruiting Phase 1

• 2 other identifiers: CTRIAL-IE-19-172019-004386-40
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Incidence of DLT within the first cycle of CPD in combination with DARA at each dose level.

  Up to cycle 1

Secondary Outcomes (1)

• MTD for pomalidomide that can safely be administered with DARA and cyclophosphamide.

  Through study treatment, an average of 1 months

Other Outcomes (1)

• RP2D for pomalidomide that can safely be administered with DARA and cyclophosphamide.

  Through study treatment, an average of 1 months

Study Arms (1)

CPD-DARA

EXPERIMENTAL

Drug: Daratumumab Other Name: Darzalex Drug: Cyclophosphamide Drug: Pomalidomide Other Name: Pomalyst/ Imnovid Drug: Dexamethasone

Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Daratumumab DRUG

Daratumumab (1,800mg) will be administered by a subcutaneous injection once every week for 2 cycles (Cycles 1-2), then once every 2 weeks for 4 cycles (Cycles 3-6), and following this (Cycle 7 onwards), patients will receive daratumumab once every four weeks.

Also known as: Darzalez

CPD-DARA

Cyclophosphamide DRUG

Cyclophosphamide will be administered PO at 50mg daily for all cohorts in the study.

CPD-DARA

Pomalidomide DRUG

Pomalidomide will be administered PO on days 1-21 of each 28 day cycle. The dose will be specified by the dose level to which the patient has been enrolled.

Also known as: Pomalyst, Imnovid

CPD-DARA

Dexamethasone DRUG

Dexamethasone will be administered PO at 40mg on days 1, 8, 15 and 22 of each 28 day cycle.

CPD-DARA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must sign an informed consent form (ICF) demonstrating that he or she understands the study and all procedures involved, and confirming he or she is willing to participate.
• Age ≥ 18 years of age.
• Confirmed diagnosis of multiple myeloma (MM) as per IMWG Criteria (Appendix C) and measurable disease defined by the following at the time of diagnosis:
• Monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma AND
• Measurable disease as defined by any of the following:
• IgG multiple myeloma (MM): serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dl or urine M-protein level ≥ 200mg/24 hours;
• IgA, IgE, IgD or IgM multiple myeloma: serum M-protein level ≥ 0.5g/dl or urine M-protein level ≥ 200mg/24 hours;
• Light chain multiple myeloma without measurable disease in the serum or the urine:
• serum immunoglobulin free light chain ≥ 10mg/dl and abnormal serum immunoglobulin kappa lambda free light chain ratio.
• ECOG (Eastern Cooperative Oncology Group) Performance Status ≤ 2 (Appendix B).
• Patients with relapsed or refractory disease IMWG Criteria (Appendix C).
• Relapsed disease (patients who achieved stable disease or better in the last line of therapy), is defined as:
• Increase of \> 25% from lowest response value in any one or more of the following:
• Serum M-component and/or (the absolute increase must be \> 5 g/L)
• Urine M-component and/or (the absolute increase must be \> 200 mg/24 h)

You may not qualify if:

• Life expectancy \< 3 months.
• Allogeneic stem cell transplantation at any time.
• Autologous stem cell transplantation within 12 weeks prior to Cycle 1 Day 1.
• Peripheral neuropathy (grade ≥ 2) as defined by the NCI CTCAE Version 5.0.
• Meningeal or Central Nervous System (CNS) involvement of myeloma.
• Acute or chronic active viral infections (Hep B, Hep C, HIV), systemic fungal infections and parasitic infections.
• Acute active infection requiring antibiotics.
• Current medical or psychiatric condition or disease that could interfere with the study procedures or results.
• Moderate or severe persistent asthma, or current uncontrolled asthma (Appendix G).
• Diagnosis of severe chronic liver disease i.e. \> stage 1 cirrhosis classified with Child-Pugh score.
• Significant heart disease including:
• Myocardial Infarction within 1 year prior to registration, or unstable / uncontrolled Ischemic Heart Disease (IHD).
• Heart failure with NYHA (New York Heart Association) grade ≥ 2 (Appendix H).
• Cardiac Arrythmia (CTCAE version 5 Grade ≥ 3 or clinically significant ECG abnormalities).
• Screening 12 lead ECG (Electrocardiogram) showing a baseline QTcF \> 470 msec.

Sponsors & Collaborators

• Cancer Trials Ireland: lead
• Janssen Pharmaceuticals: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Cork University Hospital

Cork, Ireland

Location

Beaumont Hospital

Dublin, Ireland

Location

Galway University Hospital

Galway, Ireland

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Cyclophosphamide; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 16, 2020
• Study Start: December 8, 2021
• Primary Completion: April 29, 2022
• Study Completion: April 30, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

IE (3)