A Multicenter Open Label Phase II Study of Pomalidomide and Cyclophosphamide and Dexamethasone in Relapse/Refractory Multiple Myeloma Patients Who Were First Treated Within the IFM/DFCI 2009 Trial (PCD)

NCT02244125 | Completed Phase 2 DMC

• 1 other identifier: IC 2013-05
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 30

Brief Summary

Imnovid in combination with dexamethasone is indicated in the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide (Revlimid) and bortezomib (Velcade), and have demonstrated disease progression on the last therapy. Patients with relapsed and refractory multiple myeloma who have received bortezomib, lenalidomide, dexamethasone combination, considered to be the multiple myeloma optimal treatment, can access to pomalidomide under marketing authorization only as from third line of treatment. In France this combination is not authorized for marketing for a first line treatment and only patient randomized in the IFM/DFCI 2009 trial received it. This study concerns patients previously randomized in the IFM/DFCI 2009 trial who have received bortezomib, lenalidomide and Dexamethasone combination in first line, which at progression/relapse time therapeutic opportunities remained limited and who cannot access pomalidomide under marketing authorization. This study is a multicentre, phase 2, open label, study testing the triple combination of pomalidomide and cyclophosphamide and dexamethasone (PCD) in multiple myeloma patients who are refractory or in first progression/relapse after a first line treatment with bortezomib and lenalidomide, an IMiDs (an Immuno Modulatory Drug and a proteasome inhibitor) according to the IFM/DFCI 2009 trial. In the IFM/DFCI trial, patients in arm A received eight cycles of the Velcade-Revlimid-Dexamethasone combination followed by 1 year of lenalidomide maintenance, patients in arm B received 3 cycles of Velcade-Revlimid-Dexamethasone combination plus melphalan 200mg/m2 with an autologous transplantation followed by 2 cycles of Velcade-Revlimid-Dexamethasone combination consolidation and 1 year of lenalidomide maintenance. This study will contain 3 treatment phases:

• Study treatment phase: All patients will receive 4 cycles (28 days) of pomalidomide-cyclophosphamide-dexamethasone combination.
• Consolidation phase (depends on the initial randomization in the IFM/DFCI 2009 trial):
• For patients previously randomized in IFM/DFCI 2009's arm A:
• Melphalan 200 mg/m2 followed by Autologous Transplantation
• Three months after, 2 cycles of pomalidomide-cyclophosphamide-dexamethasone combination
• For patients previously randomized in IFM/DFCI 2009's arm B:
• 5 cycles of pomalidomide-cyclophosphamide-dexamethasone combination
• Maintenance phase (identical to all patients) subsequent cycles of pomalidomide and Dexamethasone until progression / relapse or discontinuation for any other reason. For arm B patients, in case relapse occurs at least 12 months after the end of the maintenance IFM/DFCI 2009 trial, they could proceed to a second autologous transplantation and therefore follow the arm A procedure. The decision to proceed to a second transplant will be made by the physician and the patient. In order to have the same amount of patients enrolled in this trial in the initial Arm A and Arm B of the IFM/DFCI 2009 trial, once 50 patients have been included in either arm A or B, subsequent patients will be eligible if they have not been initially treated as the first 50 patients from either arm. The primary endpoint is the response rate (Partial Response (PR) or better) after 4 cycles of the triple combination pomalidomide and cyclophosphamide and dexamethasone (PCD) in the studied population using International Myeloma Working Group (IMWG) response criteria.

Conditions

Multiple Myeloma; First Relapse

Keywords

Myeloma; Multiple Myeloma; Relapse; Refractory; PCD; IFM/DFCI 2009; Transplantation; Autologous; Pomalidomide; Immunoglobulin; Ig; Free light Chain

Outcome Measures

Primary Outcomes (1)

• Response rate (Partial response (PR) or better)

  after 4 cycles of the triple association

  4 months after treatment initiation

Secondary Outcomes (1)

• Safety : incidence of Adverse Events and Serious Adverse Events and laboratory abnormalities

  from consent to 28 days after the last dose

Other Outcomes (3)

• Time to response and response duration

  every 28 days until progression/relapse or discontinuation

• Time to Disease Progression

  every 28 days until progression/relapse or discontinuation

• Overall Survival (OS)

  5 years from last study drug intake

Study Arms (2)

Previous IFM/DFCI 2009 arm A

OTHER

Patients previously randomized into IFM/DFCI 2009 trial arm A (or if transplantation was not done) will receive: * The treatment phase: * 4 cycles of PCD (Pomalidomide-Cyclophosphamide-Dexamethasone) * The consolidation phase: * Melphalan 200mg/m2 followed by ASCT (Autologous Stem Cell Transplantation) * 2 cycles of PCD (Pomalidomide-Cyclophosphamide-Dexamethasone) * The maintenance phase: Until progression or discontinuation for any other reason * Pomalidomide and Dexamethasone

Drug: PCD

Previous transplantation IFM/DFCI 2009 arm B

OTHER

Patients previously randomized into IFM/DFCI 2009 trial arm B (RVD plus Transplant) will receive: * The treatment phase: * 4 cycles of PCD (Pomalidomide-Cyclophosphamide-Dexamethasone) * The consolidation phase: * 5 cycles of PCD (Pomalidomide-Cyclophosphamide-Dexamethasone) * The maintenance phase: Until progression or discontinuation for any oher reason * Pomalidomide and Dexamethasone

Drug: PCD; Procedure: Autologous transplantation (ASCT)

Interventions

PCD DRUG

STUDY TREATMENT PHASE: All patients * 4x 28 days cycles of PCD \[Pomalidomide: 4mg/day oral route on 21 days per cycle\] \[Cyclophosphamide: 300mg/day oral route on days 1, 8, 15, 22 per cycle\] \[Dexamethasone: 40mg/day oral route on days 1, 2, 3, 4 and 15, 16, 17, 18 per cycle\] CONSOLIDATION PHASE: depends on previous IFM/DFCI 2009's arm: Arm A: * Melphalan 200mg/m2 followed by Autologous Transplantation * 2x 28 days cycles of PCD, three months post transplantation Arm B: * 5x 28 days cycles of PCD \[Pomalidomide: 4mg/day oral route on 21 days per cycle\] \[Cyclophosphamide: 300mg/day oral route on days 1, 8, 15, 22 per cycle\] \[Dexamethasone: 40mg/day oral route on days 1, 8, 15, 22 per cycle\] MAINTENANCE PHASE: All patients \- Until progression/relapse or discontinuation for any other reason \[Pomalidomide: 4mg/day oral route on 21 days per cycle\] \[Dexamethasone: 20mg/day oral route on days 1, 8, 15, 22 per cycle\]

Also known as: Pomalidomide-Cyclophosphamide-Dexamethasone association

Previous IFM/DFCI 2009 arm A; Previous transplantation IFM/DFCI 2009 arm B

Autologous transplantation (ASCT) PROCEDURE

Arm A: •Melphalan 200mg/m2 followed by Autologous Transplantation

Previous transplantation IFM/DFCI 2009 arm B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have been treated in first line within the IFM/DFCI 2009 trial to be treated within the PCD trial in second line
• Must be able to understand and voluntarily sign an informed consent form
• Must be able to adhere to the study visit schedule and other protocol requirements
• Age: 18-70 years
• Life expectancy \>6 months
• Patients must have progressive (+/- symptomatic) Myeloma as defined by the IMWG criteria with 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 ≥0.5 g/dl)
• Urine M-component and/or (the absolute increase must be ≥200 mg/24h)
• Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 mg/dl
• Bone marrow plasma cell percentage; the absolute percentage must be ≥10%
• Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
• Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dl or 2.65mmol/l) that can be attributed solely to the plasma cell proliferative disorder.
• Patients must have a clearly detectable and quantifiable monoclonal M-component value:
• IgG (serum M-component \>10g/l)
• IgA (serum M-component \>5g/l)

You may not qualify if:

• Any other uncontrolled medical condition or comorbidity that might interfere with subject's participation
• Primary amyloidosis or myeloma complicated by amyloidosis
• Pregnant or breast feeding females
• Use of any other experimental drug or therapy within 2 weeks before study treatment initiation (except local radiotherapy and/or corticosteroid until dose of dexamethasone 160mg)
• Known positive for HIV or Active infectious hepatitis, type B or C
• Patients with non-secretory MM
• Prior history of malignancies within 10 years
• Evidence of Central Nervous System (CNS) involvement
• Any \>grade 2 toxicity unresolved
• Peripheral neuropathy \>grade 2
• Known hypersensitivity to thalidomide, lenalidomide, cyclophosphamide or dexamethasone
• Ongoing active infection, especially ongoing pneumonitis
• Participant with clinical signs of heart or coronary failure, or evidence of Left Ventricular Ejection Fraction (LVEF) inferior to 40%.
• Participant with myocardial infarction within 6 months prior to enrolment or have New York Heart Association (NYHA) Class III or IV heart failure, and controlled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Inability or unwillingness to comply with birth control requirements

Sponsors & Collaborators

• Institut Curie: lead
• Intergroupe Francophone du Myelome: collaborator
• Celgene Corporation: collaborator

Study Sites (30)

CHRU Hopital Sud

Amiens, 80054, France

Location

Centre Hospitalier de la côte Basque

Bayonne, 64109, France

Location

Hôpital Avicenne

Bobigny, 93009, France

Location

ICH - Hôpital A. Morvan

Brest, 29609, France

Location

Institut d'Hématologie de Basse Normandie - IHBN

Caen, 14033, France

Location

Chu Estaing

Clermont-Ferrand, 63003, France

Location

CHU Henri Mondor

Créteil, 94010, France

Location

CHRU Dijon

Dijon, 21000, France

Location

Centre Hospitalier Général

Dunkirk, 59385, France

Location

Chru Grenoble

Grenoble, 38043, France

Location

Centre Hospitalier départemental de Vendée

La Roche-sur-Yon, 85925, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

CHRU - Hôpital Claude Huriez

Lille, 59037, France

Location

CHU de Limoges

Limoges, 87042, France

Location

Institut Paoli Calmette

Marseille, 13273, France

Location

Hopital Emile Muller

Mulhouse, 68100, France

Location

CHU de Nantes

Nantes, 44093, France

Location

CHU Carémeau

Nîmes, 30029, France

Location

Institut Curie

Paris, 750005, France

Location

CHRU Hopital Saint Antoine

Paris, 75012, France

Location

CHRU Hôpital Haut Lévêque

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier Annecy Genevois

Pringy, 74374, France

Location

CHRU Hopital Pontchaillou

Rennes, 35033, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Centre Hospitalier Yves Le Foll

Saint-Brieuc, 22027, France

Location

Centre René Huguenin

Saint-Cloud, 92210, France

Location

Institut Universitaire du Cancer Toulouse-Oncopôle (IUCT-O)

Toulouse, 31059, France

Location

CHRU Hopital Bretonneau

Tours, 37044, France

Location

CHRU Hopitaux de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Related Publications (2)

• Garderet L, Kuhnowski F, Berge B, Roussel M, Devlamynck L, Petillon MO, Escoffre-Barbe M, Lafon I, Facon T, Leleu X, Karlin L, Perrot A, Stoppa AM, Royer B, Chaleteix C, Tiab M, Araujo C, Lenain P, Macro M, Belhadj K, Ikhlef S, Hulin C, Loiseau HA, Attal M, Moreau P. Pomalidomide and dexamethasone until progression after first salvage therapy in multiple myeloma. Br J Haematol. 2023 Jun;201(6):1103-1115. doi: 10.1111/bjh.18772. Epub 2023 Mar 27.

  PMID: 36974007 RESULT

• Garderet L, Kuhnowski F, Berge B, Roussel M, Escoffre-Barbe M, Lafon I, Facon T, Leleu X, Karlin L, Perrot A, Moreau P, Marit G, Stoppa AM, Royer B, Chaleteix C, Tiab M, Araujo C, Lenain P, Macro M, Voog E, Benboubker L, Allangba O, Jourdan E, Orsini-Piocelle F, Brechignac S, Eveillard JR, Belhadj K, Wetterwald M, Pegourie B, Jaccard A, Eisenmann JC, Glaisner S, Mohty M, Hulin C, Loiseau HA, Mathiot C, Attal M. Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma. Blood. 2018 Dec 13;132(24):2555-2563. doi: 10.1182/blood-2018-07-863829. Epub 2018 Oct 3.

  PMID: 30282798 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Recurrence

Interventions

Transplantation, Autologous

Condition Hierarchy (Ancestors)

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Transplantation; Surgical Procedures, Operative

Study Officials

• KUHNOWSKI Frederique, MD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2014
• First Posted: September 18, 2014
• Study Start: April 14, 2014
• Primary Completion: January 1, 2017
• Study Completion: May 29, 2023
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (30)