IFM 2020-01 (Isamyp) Efficacity assessment of isatuximab plus pomalidomide and dexamethasone in patients with AL amyloidosis who didn't reach at least a very good partial response with their previous treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intergroupe Francophone Du Myelome

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

completed 30 Jan 2026

Decision date (initial)

2024-11-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Bristol Myers Squibb · Sanofi Winthrop Industrie

External identifiers

EU CT number

2024-513887-25-00

EudraCT number

2020-004333-20

ClinicalTrials.gov

NCT05066607

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To assess hematologic response (VGPR or better i.e. dFLC < 40 mg/L, CR including modified CR, low-dFLC response (dFLC < 10 mg/L), iFLC < 10 mg/L) achieved after 6 cycles of Isa-Pd

Secondary objectives 7

1. To assess in all patients according to their disease history Overall Hematologic Response Rate (VGPR, CR, modified CR*, Low-dFLC response (dFLC < 10 mg/L), iFLC < 10 mg/L and PR) at the completion of the 1st, 2nd, 4th, 6th, 9th and 12th cycles.
2. To evaluate the following preliminary efficacy measures following treatment with Isa-Pd: - Hematologic Progression-free survival (PFS) and 1-year PFS - Relapse-free survival (RFS) - Organ response rate (OrRR) at 1 year - Overall survival (OS) and 1-year OS - Time to and duration of hematologic and organ responses
3. To determine safety and tolerability of Isatuximab plus Pomalidomide and Dexamethasone (type, frequency, severity, drug discontinuation for toxicity or intolerance, dose modification/delay and relationship of adverse events to study treatment).
4. To assess the impact of t(11.14) determined by NGS sequencing or FISH at inclusion on response.
5. To assess correlation of Strain improvement to NT-proBNP after 6 cycles of IsaPd and at 1 year from start of therapy or 12 cycles of IsaPd
6. To assess albumin level to proteinuria/eGFR after 6 cycles of IsaPd and at 1 year from start of therapy or 12 cycles of IsaPd
7. To assess Quality of Life (EQ-5D-3L questionnaire).

Conditions and MedDRA coding

AL Amyloidosis

Regulatory references

Plan to share IPD

Yes

IPD plan description

All data processing is MR001 compliant.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥ 18
2. Histologic diagnosis of AL amyloidosis;
3. Patients should have received at least one line with an alkylating agent and/or a PI, and/or with an anti-CD38 which the last administration ≥ 1 year before the C1D1 and dexamethasone and not be in VGPR (or better) at the time of inclusion (patients who did not reach VGPR before, or patients in VGPR or better before but with a hematological relapse at the time of inclusion can be included);
4. Measurable hematologic disease: difference between involved and uninvolved FLC > 50 mg/L with an abnormal k/l ratio;
5. Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system)
6. Wash‐out period of at least 4 weeks from previous antitumor therapy or any investigational treatment or 5 half‐lives from previous antibodies, whichever is longer.
7. Adequate bone marrow function prior to 1st drug intake (C1D1), without transfusion or growth factor support within 5 days prior to 1st drug intake, defined as: - Absolute neutrophils count ≥ 1000/mm3, - Platelets ≥ 75000/mm3, - Hemoglobin ≥ 8.0 g/dL,
8. Adequate organ function defined as: - Serum ASAT and ALAT ≤ 3.0 X Upper Limit of the normal range (ULN), - Serum total bilirubin level < 1.5 x ULN, unless for subjects with Gilbert’s syndrome where the direct bilirubin should then be ≤ 2.0 x ULN.
9. ECOG status ≤ 2
10. Male participants must agree to use contraception during the intervention period and for at least 5 months after the last dose of IsaPd and refrain from donating sperm during this period. Female participants are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies: - Not a Female of childbearing potential (FCBP), OR a FCBP who must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 – 14 days prior to and again within 24 hours prior to starting study medication and before each cycle of study treatment and must either commit to continue complete abstinence from heterosexual intercourse or apply two reliable methods of birth control (One highly effective method and one additional effective method) used at the same time, beginning 4 weeks before initiation of treatment, during the intervention period and for at least 5 months after IsaPd treatment, Serum pregnancy test must be performed for all women of childbearing potential within 24 hours prior to the start of the treatment, weekly for the first 28 days of treatment and then, every 28 days while on treatment, during dose interruption, then at study discontinuation and at day 28 after end of treatment. In addition, a pregnancy test may be done at any time during the study at the discretion of the investigator if a subject misses a period or has unusual menstrual bleeding.
11. 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.

Exclusion criteria 21

1. Presence of non-AL amyloidosis
2. Undergoing dialysis
3. Ongoing toxicity (excluding alopecia and those listed in eligibility criteria) from any prior therapy > G1 (NCI-CTCAE v5.0)
4. Supine systolic blood pressure < 90 mmHg, or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of < 80 mmHg despite medical management (i.e. midodrine, fludrocortisones) in the absence of volume depletion
5. 13. Previous anti-CD38 therapy < 1 year before the C1D1 or Pomalidomide therapy (if refractory to Pomalidomide and/or anti-CD38 therapy)
6. Hypersensitivity to IMiD® or anti-CD38 defined as any hypersensitivity reaction leading to stop IMiD® or anti-CD38 within the 2 first cycles or toxicity, which does meet intolerance definition
7. Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, polysorbate 80, poloxamer 188, sucrose or any of the other components of study treatment that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents
8. AL amyloidosis with isolated soft tissue involvement
9. Bone marrow plasma cells >30% or symptomatic multiple myeloma
10. NT-proBNP > 8500 ng/L and hs-troponin I > 100 ng/L or hs-troponin T > 50 ng/L (cardiac stage IIIb patients)
11. Repetitive ventricular arrhythmias on 24h Holter ECG despite anti‐arrhythmic treatment sustained ventricular tachycardia, aborted ventricular fibrillation, atrioventricular nodal or sinoatrial nodal dysfunction with no pacemaker
12. Chronic atrial fibrillation with uncontrolled heart rate
13. Significant cardiac dysfunction; myocardial infarction within 12 months; unstable poorly controlled angina pectoris
14. Uncorrected valvular disease unrelated to AL amyloid cardiomyopathy
15. QT interval as corrected by Fridericia’s formula > 550 msec without pacemaker,
16. History of malignancy (other than AL amyloidosis) within 3 years before the date of inclusion (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)
17. Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results
18. Active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics
19. Received any investigational drug within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer. In case of very aggressive disease (i.e acute leukemia) delay could be shortened after agreement between sponsor and investigator, in absence of residual toxicities from previous therapy
20. Known positive for HIV or active hepatitis A, B or C: • Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA Of note: Patient can be eligible if anti-HBc IgG positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative. o If anti-HBV therapy in relation with prior infection was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatment period. Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met. • Active HCV infection: positive HCV RNA and negative anti-HCV. Of note: Patients with antiviral therapy for HCV started before initiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion. Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible
21. Pregnant or breast-feeding females

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. VGPR or better (i.e. dFLC < 40 mg/L) assessed using consensus response criteria (Appendix 2) at the end of 6 cycles

Secondary endpoints 10

1. Overall Hematologic Response Rate (VGPR, CR, modified CR, Low-dFLC response (dFLC < 10 mg/L), iFLC < 10mg/L and PR assessed using consensus criteria (Appendix 2), at the completion of the 1st, 2nd, 4th, 6th, 9th and 12th cycles
2. Relapse Free Survival in responding population measured from the date of best response
3. Progression Free Survival measured from the date of inclusion
4. Organ response rate (OrRR) at 1 year according to current consensus criteria
5. Overall Survival measured from the date of inclusion
6. Time to and duration of hematologic and organ responses
7. Type, frequency, severity (NCI-CTCAE v5.0), drug discontinuation for toxicity or intolerance, dose modification/delay and relationship of adverse events to study treatment.
8. Left ventricular strain assessed by transthoracic echocardiography (TTE) after 6 cycles of IsaPd and at 1 year from start of therapy or 12 cycles of IsaPd
9. Albumin level and proteinuria assessed by electrophoresis eGFR estimated by CKD epi after 6 cycles of IsaPd and at 1 year from start of therapy or 12 cycles of IsaPd
10. Health‐related QoL and potential for improvement over the course of the study assessed by the EQ‐5D‐3L patient‐reported outcome questionnaire

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intergroupe Francophone Du Myelome

Sponsor organisation

Intergroupe Francophone Du Myelome

Address

75 Avenue Parmentier

City

Paris Cedex 11

Postcode

75544

Country

France

Scientific contact point

Organisation

Intergroupe Francophone Du Myelome

Contact name

Pr Arnaud JACCARD

Public contact point

Organisation

Intergroupe Francophone Du Myelome

Contact name

Léa Tabone

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications