IPD in RRMM Characterized with Genomic Abnormalities of Adverse Prognostic

NCT03683277 | Terminated Phase 2 DMC

• 1 other identifier: IFM 2014-01
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 28

Brief Summary

This study is a Multicenter, Open-label, Phase II study of ixazomib, plus Pomalidomide and Dexamethasone regimen (IPD) in RRMM with adverse Genomic Abnormalities.

Conditions

Multiple Myeloma; Relapsed and Refractory Multiple Myeloma; Genetic Condition

Outcome Measures

Primary Outcomes (1)

• Time to disease progression (TTP) to IPD in RRMM with adverse Genomic Abnormalities

  Time to progression (TTP), defined as time from the first induction cycle to confirmed progressive disease (PD) per the International Myeloma Working Group criteria, or death due to progressive disease, whichever occurs first. It is noted that the events (PD or death due to PD) may include those that occur in the maintenance phase. The analysis will be performed on an Intent-To-Treat (ITT) basis and then per protocol

  from Cycle 1 Day 1 of Induction phase (each Cycle is 21 days) until documented disease progression or death due to disease progression, whichever came first, assessed through study completion, an average of 18 months

Secondary Outcomes (10)

• Incidence of Serious Adverse Events and Adverse Events as assessed by CTCAE version 4.0, dose reduction or modification

  after the 10th patient has completed the first cycle of treatment (Cycle is 21 days), an average of 5 months after the beginning of the study and then every 6 months through study end

• Plasma concentrations of ixazomib after twice-weekly dosing in combination with Pomalidomide and Dexamethasone

  from Cycle 1 Day 1 to Cycle 5 day 1 of Induction phase (each cycle is 21 days)

• Overall Response rate (ORR, Partial Response and better) to IPD

  after completion of induction treatment of the last patient included, an average of 2 years after the beginning of the study and post maintenance treatment of the last patient included, an average of 3 years and half after the beginning of the study

• Very Good Partial Response (VGPR) rate to IPD

  after completion of induction treatment of the last patient included, an average of 2 years after the beginning of the study and post maintenance treatment of the last patient included, an average of 3 years and half after the beginning of the study

• Complete Response (CR) rate to IPD

  after completion of induction treatment of the last patient included, an average of 2 years after the beginning of the study and post maintenance treatment of the last patient included, an average of 3 years and half after the beginning of the study

Other Outcomes (4)

• Response rate to IPD with to genomic abnormalities in the bone marrow tumor plasma cells.

  from the start of study treatment to the termination of the study, an average of 5 years

• Survival rate to IPD with to genomic abnormalities in the bone marrow tumor plasma cells.

  from the start of study treatment to the termination of the study, an average of 5 years

• Define the molecular characteristics of the 2 groups, ER and PR to IPD

  from the start of study treatment to the termination of the study, an average of 5 years

Study Arms (1)

Ixazomib/Pomalidomide/Dexamethasone

EXPERIMENTAL

Single arm treatment organized in 2 separate phases Induction phase : association of Ixazomib, Pomalidomide \& Dexamethasone (IPD) 21-days cycles - maximum of 17 cycles Ixazomib (tablets) 3 mg D1, D4, D8 and D11 Pomalidomide (tablets) 4mg D1 to D14 Dexamethasone (tablets) 40 mg/d D1, D8 and D15 if patient aged \<75 years or Dexamethasone (tablets) 20 mg/d D1, D8 and D15 if patient aged ≥ 75 years Maintenance phase : association of Ixazomib and Pomalidomide (IP) 28-days cycles until disease progression Ixazomib (tablets) 4mg D1, D8 and D15 Pomalidomide (tablets) 4mg D1 to D21

Drug: Ixazomib/Pomalidomide/Dexamethasone

Interventions

Ixazomib/Pomalidomide/Dexamethasone DRUG

Treatment with association of Ixazomib, Pomalidomide and Dexamethasone (IPD) Induction phase : 21-days cycles - maximum of 17 cycles Ixazomib (tablets) 3 mg D1, D4, D8 and D11 Pomalidomide (tablets) 4mg D1 to D14 Dexamethasone (tablets) 40 mg/d D1, D8 and D15 if patient aged \<75 years Dexamethasone (tablets) 20 mg/d D1, D8 and D15 if patient aged ≥ 75 years Treatment with association of Ixazomib and Pomalidomide (IP) Maintenance phase : 28-days cycles until disease progression Ixazomib (tablets) 4mg D1, D8 and D15 Pomalidomide (tablets) 4mg D1 to D21

Also known as: Multicentric, phase 2, RRMM, refractory, relapse, myeloma

Ixazomib/Pomalidomide/Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Male or female patients 18 years or older.
• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Life expectancy \> 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2.
• Presence - at diagnosis or at relapse - of one of the following adverse genomic abnormalities determined using Interphase fluorescence in situ hybridization and Single nucleotide polymorphism (FISH/SNP) techniques at a significant rate validated centrally by Pr AVET - LOISEAU:
• deletion 17p
• and/ or translocation (4; 14)
• Must have an RRMM and have received a Lenalidomide line of treatment
• Must have a Progressive Multiple Myeloma (MM) according to IMWG consensus recommendations for multiple myeloma treatment response criteria (DURIE 2007, RAJKUMAR 2011) :
• Increase of 25% from lowest response value in any one of the following:
• Serum M-component (absolute increase must be ≥ 0.5 g/dL),
• Urine M-component (absolute increase must be ≥ 200 mg/24 hours),
• Only in subjects without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC (Free Light-Chain) levels (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

You may not qualify if:

• Any other uncontrolled medical condition or comorbidity that might interfere with subject's participation.
• Patients not having receive Lenalidomide
• Pregnant or breast feeding females
• Known positive for HIV or active hepatitis type B or C.
• Patients with non-secretory MM
• Patient with terminal renal failure that require dialysis and clearance creatinine \< 30ml/min
• Prior history of malignancies, other than multiple myeloma, unless the patients has been free of the disease for ≥ 5 years.
• Prior local irradiation within two weeks before first dose\*
• \*However, an exception (that is patients allowed to remain in the treatment phase of the study) is made for radiation therapy to a pathological fracture site to enhance bone healing or to treat post-fracture pain that is refractory to narcotic analgesics because pathologic bone fractures do not by themselves fulfill a criterion for disease progression.)
• Evidence of central nervous system (CNS) involvement
• Unable to take corticotherapy at study entry, Ixazomib or pomalidomide
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
• Ongoing Cardiac dysfunction: specify e.g. uncontrolled hypertension, MI (Myocardial Infarction) within 6 months, unstable Angina pectoris, Cardiac arrhythmia Grade 2 or higher
• Patients planned to receive a transplantation while on IPd protocol
• Patients who have had Ixazomib and Pomalidomide therapy as a previous line

Sponsors & Collaborators

• Intergroupe Francophone du Myelome: lead
• AXONAL: collaborator
• Nantes University Hospital: collaborator
• University Hospital, Grenoble: collaborator
• Euraxi Pharma: collaborator
• QPS Holdings LLC: collaborator
• Bristol-Myers Squibb: collaborator
• Takeda: collaborator

Study Sites (28)

CHU Angers

Angers, 49033, France

Location

CH Avignon - Centre Hospitalier H.Duffaut

Avignon, 84000, France

Location

Centre hospitalier de la côte basque

Bayonne, 64109, France

Location

Hôpital Avicenne

Bobigny, 93009, France

Location

CHU de Caen

Caen, 14033, France

Location

Hôpital Privé Sévigné

Cesson-Sévigné, 35510, France

Location

CHU Henri Mondor

Créteil, 94010, France

Location

CHU de Dijon

Dijon, 21000, France

Location

Centre hospitalier de Dunkerque

Dunkirk, 59386, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

Centre hospitalier départemental de Vendée

La Roche-sur-Yon, 85925, France

Location

CHRU Hôpital Claude Huriez

Lille, 59037, France

Location

CHU de Limoges

Limoges, 87042, France

Location

CHU Saint Eloi

Montpellier, 34295, France

Location

CHRU Hôtel Dieu

Nantes, 44035, France

Location

Hôpital de l'Archet 1

Nice, 06202, France

Location

Hôpital Saint Louis

Paris, 75475, France

Location

CHU Bordeaux - Hôpital Haut Leveque

Pessac, 33604, France

Location

Centre Hospitalier de Périgueux

Périgueux, 24019, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Poitiers

Poitiers, 86021, France

Location

CHU de Reims Hôpital Robert Debré

Reims, 51092, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Institut de cancérologie Strasbourg Europe (ICANS)

Strasbourg, 67091, France

Location

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, 31059, France

Location

CHRU Bretonneau

Tours, 37044, France

Location

Hôpitaux de Brabois - CHRU de Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

Related Publications (39)

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  BACKGROUND

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  BACKGROUND

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MeSH Terms

Conditions

Multiple Myeloma; Recurrence; Genetic Diseases, Inborn

Interventions

ixazomib; Clinical Trials, Phase II as Topic

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Xavier LELEU, Pr

  Poitiers University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: All the patients will receive the same treatment until disease progression or end of study

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: September 25, 2018
• Study Start: November 3, 2019
• Primary Completion: December 31, 2022
• Study Completion: February 10, 2023
• Last Updated: February 19, 2025

Record last verified: 2023-06

Locations

FR (28)