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)

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

Interventions

DRUG

PCD

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 \[Pomalidomide: 4mg/day oral route on 21 days per cycle\] \[Dexamethasone: 20mg/day oral route on days 1, 8, 15, 22 per cycle\]

PROCEDURE

Autologous transplantation (ASCT)

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

Sponsors & Collaborators

• Intergroupe Francophone du Myelome

  collaborator NETWORK

• Celgene Corporation

  collaborator INDUSTRY

• Institut Curie

  lead OTHER

Principal Investigators

• KUHNOWSKI Frederique, MD · Institut Curie

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-04-14

Primary Completion

2017-01-31

Completion

2023-05-29

Countries

• France

Study Locations