I2D IFM2021_03: A Multi-center Open-label Phase 2 Study of Ixazomib, Iberdomide and Dexamethasone in Elderly Patients With Multiple Myeloma at First Relapse."

Sponsor

Nantes University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04998786

Collaborator

(none)

Enrollment

Locations

Arm

60.6

Anticipated Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase II, multicenter, open-label study to evaluate the rate of patients achieving very good partial response (VGPR) or better to the oral combination Iberdomide Ixazomib Dexamethasone in elderly patients with multiple myeloma at first relapse .

The patient population will consist of adult men and women more than 70 years, who meet eligibility criteria.

Following the screening period, patients will be enrolled and treated then, they will receive therapy with Iberdomide, Ixazomib and Dexaméthasone during 6 cycles and Iberdomide and Ixazomib until progression.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma at First Relapse	Drug: Ixazomib Drug: Iberdomide Drug: Dexamethasone Oral	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multi-center Open-label Phase 2 Study of Ixazomib, Iberdomide and Dexamethasone in Elderly Patients With Multiple Myeloma at First Relapse."

Actual Study Start Date :

Dec 14, 2021

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: assessment of treatment Ixazomib, dexamethasone, iberdomide Iberdomide, Ixazomib and Dexaméthasone during 6 cycles and Iberdomide and Ixazomib until progression	Drug: Ixazomib Ixazomib 3 mg/day (days 1, 8, 15) cycle 1 to until progress Drug: Iberdomide Iberdomide 1.6 mg / day (day 1 to 21) cycle 1 to until progress Drug: Dexamethasone Oral Cycle 1 and 2 Dexaméthasone 20 mg/day on days 1, 8, 15, 22 Cycle 3 to 6 Dexamethasone 10 mg/day on days 1, 8, 15, 22

Arm

Intervention/Treatment

Experimental: assessment of treatment Ixazomib, dexamethasone, iberdomide

Iberdomide, Ixazomib and Dexaméthasone during 6 cycles and Iberdomide and Ixazomib until progression

Drug: Ixazomib

Ixazomib 3 mg/day (days 1, 8, 15) cycle 1 to until progress

Drug: Iberdomide

Iberdomide 1.6 mg / day (day 1 to 21) cycle 1 to until progress

Drug: Dexamethasone Oral

Cycle 1 and 2 Dexaméthasone 20 mg/day on days 1, 8, 15, 22 Cycle 3 to 6 Dexamethasone 10 mg/day on days 1, 8, 15, 22

Outcome Measures

Primary Outcome Measures

Percentage of patients have very good partial response (VGPR) or better [approximate 18 months]
Using IMWG criteria

Secondary Outcome Measures

Number of adverse events [approximate 18 months]
Number of adverse events defined by Common Terminology Criteria for Adverse Events (v5)
Number of responses [3 months]
Partial Response (PR), Very Good Partial Response (VGPR), Complete Response (CR) and minor response (MR) will be evaluated according to IMWG
Number of responses [6 months]
Partial Response (PR), Very Good Partial Response (VGPR), Complete Response (CR) and minor response (MR) will be evaluated according to IMWG
Number of the death [approximate 18 months]
is defined as the time in months from inclusion to the date of death due to any cause. Subject alive will be censored at the last known alive date.
Number of progression [approximate 18 months]
is defined as the time in months from inclusion to the date of disease progression or death due to any cause, using IMWG criteria
Percentage of time to progression [approximative 18 months]
is defined as the time in months from inclusion to the date of disease progression or death due to any cause, using IMWG criteria
Percentage of duration of response [approximative 18 months]
is defined as the time from the first response (PR or better) to the date of disease progression or death due to any cause
Percentage of duration of therapy [approximative 18 months]
is defined as the time from treatment initiation to the last dose of therapy
Percentage of time to response [approximative 18 months]
according IMWG
Percentage of Overall Response Rate [approximative 18 months]
according IMWG
Percentage of value of biological prognostic factors [day 1]
prognostic factors as ISS stage, cytogenetic as del(17p), t(4;14),
Percentage of frailty scores [day 1]
age, ECOG, comorbidity index
Percentage of score of quality of life [approximative 18 months]
To assess Quality of Life EQ5D and SF36

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 70 years
Eastern Collaborative Oncology Group (ECOG) performance score of ≤2
Life expectancy > 6 months
Voluntary written informed consent must be given before performance of any study-related procedure not part of normal medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.
Symptomatic multiple myeloma (MM) at first relapse, as defined below:

Symptomatic multiple myeloma according to international criteria.(Rajkumar et al,

Relapsed MM is defined as previously treated MM that progresses and requires initiation of salvage therapy.

Subject must have received one prior line of therapy for at least 3 cycles.
Subject has measurable disease at Screening, defined at least one of the following:

Serum M-protein ≥ 0.5 gram (g)/deciliter (dL), OR
Urine M-protein ≥ 200 mg in 24 hours, OR
Serum immunoglobulin free light chain (FLC) ≥ 10 mg/dL provided serum FLC ratio is abnormal.

Subjects must meet the following laboratory parameters, per laboratory reference range (performed at most 15 days before cycle 1 day 1):

Absolute neutrophil count (ANC) ≥ 1000/microliter (μL). Subjects may use growth factor support to achieve ANC eligibility criteria.
Platelet count ≥ 75,000 /mm3 for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count ≥ 50,000/mm3 for subjects in whom > 50% of bone marrow nucleated cells are plasma cells. It is not permissible to transfuse subjects to achieve minimum platelet counts within 3 days before study.

--AST and ALT ≤ 3 × upper limit of normal (ULN).

Total bilirubin ≤ 1.5 × ULN. Subjects with documented Gilbert's syndrome may have bilirubin > 1.5 × ULN with the approval of the Primary Therapeutic Area Medical Director
Creatinine clearance (CrCl) ≥ 30 milliliter (mL)/minute (min) (using Cockroft and Gault Formula)

Patient should comply with Celgene's pregnancy prevention plan for Iberdomide (please see appendix 8 Iberdomide Pregnancy Prevention Plan for subjects in clinical trials)
Female patients who:

are postmenopausal for at least 24 months before the screnning visit, OR
are surgically sterile (have undergone a hysterectomy or bilateral oophorectomy)

Men even if surgically sterilized must agree to not father a child and agree to practice complete abstinence or to use a condom during therapy and dose interruptions and for 90 days after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential or pregnant.

Non-inclusion Criteria:

Subject is refractory to bortezomib, defined as progression on or within 60 days of the last dose of bortezomib.
Subject has had prior treatment with ixazomib, carfilzomib, pomalidomide or iberdomide
Subject has any of the following conditions:

Non-secretory or oligo-secretory MM
Light chain Amyloidosis (AL Amyloidosis)
POEMS syndrome Waldenström macroglobulinemia

Known Human Immunodeficiency Viral (HIV) infection
Active hepatitis B or C infection based on blood screen tests
Significant cardiovascular or pericardial disease, including uncontrolled angina, hypertension, arrhythmia, recent myocardial infarction within 6 months, congestive, heart failure New York Heart Association (NYHA) Class ≥ 3
Major surgery within 4 weeks prior screening
Acute infections requiring parenteral therapy (antibiotic, antifungal or antiviral) within 14 days
≥ Grade 3 Peripheral neuropathy or grade 2 with pain
Uncontrolled diabetes or uncontrolled hypertension within 14 days
Any other medical condition that, in the opinion of the Investigator, would adversely affect the subject's participation in the study
Subject has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions:

Adequately treated in situ carcinoma of the cervix uteri or the breast,
Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin,
Prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment,
Previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study.

Known intolerance to steroid therapy
Serious medical or psychiatric illness likely to interfere with participation in study
Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs
Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision

Contacts and Locations

Locations

	Site	City	Country
1	CHR	Annecy	France
2	CH de la cote basque	Bayonne	France
3	CHRU Hopital Haut Lévêque	Bordeaux	France
4	CHU de Brest	Brest	France
5	CHU	Caen	France
6	CHU	Clermont-Ferrand	France
7	CHRU	Dijon	France
8	CHD les Oudairies	La Roche-sur-Yon	France
9	CHRU Lille	Lille	France
10	CHU	Limoges	France
11	CH Lyon Sud	Lyon	France
12	CHRU	Nancy	France
13	CHU	Nantes	France
14	Hopital de l'archet	Nice	France
15	CHU Henri Mondor	Paris	France
16	Hopital St Antoine	Paris	France
17	Hopital St Louis APHP	Paris	France
18	University Hospital	Poitiers	France
19	CHRU	Rennes	France
20	ICANS	Strasbourg	France
21	CHU	Toulouse	France