AL AmyloidosisPhase 2IsAMYPNCT05066607
Isatuximab Plus Pomalidomide and Dexamethasone Association for Patients With AL Amyloidosis Not in VGPR or Better After Any Previous Therapy
A Phase 2 study testing Isatuximab in people with AL Amyloidosis, run by Intergroupe Francophone du Myelome at 15 sites in France.
Trial summary
This phase 2 study ain to evaluate the efficacy of Isatuximab plus Pomalidomide and Dexamethasone (IPd), in patients with AL amyloidosis not in VGPR or better after any previous therapy. It will enrolled 46 patients (34 in France and 12 in Australia) through 15 sites (11 in France and 4 in Australia). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AL Amyloidosis
- What is being tested?
- Isatuximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 15 sitesFrance
- Study dates
- 11 Feb 2022to Mar 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18
- Histologic diagnosis of AL amyloidosis;
- Patients should have received at least one line with an alkylating agent and/or a PI, 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);
- Measurable hematologic disease: difference between involved and uninvolved FLC > 50 mg/L with an abnormal k/l ratio;
- Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system) (See Appendix 1);
- 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.
Show all 18Show fewer
- 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,
- Adequate organ function defined as:
- Serum ASAT or 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.
- ECOG status ≤ 2
- 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 abstinence from heterosexual intercourse or apply a highly effective method of birth control 4 weeks before initiation of treatment, during the intervention period and for at least 5 months after IsaPd treatment,
- Female patients who are postmenopausal for at least 1 year before the screening visit, or are surgically sterile, or if they are of childbearing potential, agree to practice effective methods of contraception from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to completely abstain from intercourse (serum pregnancy test must be performed for all women of childbearing potential at the beginning of each cycle during the study. 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);
- 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.
Who cannot join
- Presence of non-AL amyloidosis
- AL amyloidosis with isolated soft tissue involvement
- Bone marrow plasma cells >30% and clinically symptomatic multiple myeloma with lytic bone lesions
- NT-proBNP > 8500 ng/L and hs-troponin I > 100 ng/L or hs-troponin T > 50 ng/L (cardiac stage IIIb patients)
- 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
- Chronic atrial fibrillation with uncontrolled heart rate
Show all 30Show fewer
- Significant cardiac dysfunction; myocardial infarction within 12 months; unstable poorly controlled angina pectoris
- Uncorrected valvular disease unrelated to AL amyloid cardiomyopathy
- QT interval as corrected by Fridericia's formula >550 msec without pacemaker,
- Undergoing dialysis
- Ongoing toxicity (excluding alopecia and those listed in eligibility criteria) from any prior therapy >G1 (NCI-CTCAE v5.0)
- Supine systolic blood pressure <90 mm Hg, 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
- Previous anti-CD38 therapy or Pomalidomide therapy (if refractory to Pomalidomide)
- Hypersensitivity to IMiD® defined as any hypersensitivity reaction leading to stop IMiD® within the 2 first cycles or toxicity, which does meet intolerance definition
- 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
- 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)
- 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
- Active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics
- 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
- 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.
- 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
- Pregnant or breast-feeding females
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
France15 sites, 15 recruiting
- Not yet recruiting
CHU Amiens-Picardie
Amiens, 80054
Pierre MOREL, Dr., 03 22 45 59 14 ext. +33, Morel.Pierre@chu-amiens.fr
- Not yet recruiting
CHRU - Hôpital du Bocage
Angers
Mamoun Dib, Dr, 02 41 35 47 05 ext. +33, madib@chu-angers.fr
- Not yet recruiting
CHU Caen - Côte de Nacre
Caen
Dr. Macro, 02.31.27.21.22, macro-m@chu-caen.fr
- Not yet recruiting
Groupe Hospitalier Mutualiste de Grenoble
Grenoble, 38028
Cécile LEYRONNAS, Dr., 04 76 70 73 43 ext. +33, cecile.leyronnas@avec.fr
- Not yet recruiting
CHRU Hôpital Claude Huriez
Lille
Salomon MANIER, Dr., 03 20 44 57 13 ext. +33, salomon.manier@chru-lille.fr
- Not yet recruiting
Centre Hospitalier Universitaire (CHU) de Limoges
Limoges
Pr. Jaccard, 05.55.05.88.62, arnaud.jaccard@chu-limoges.fr
- Not yet recruiting
Centre Hospitalier Lyon Sud
Lyon
Dr. Karlin, 04.48.86.43.09, lionel.karlin@chu-lyon.fr
- Not yet recruiting
Hopital Saint Eloi - CHU Montpellier
Montpellier
Dr. Vincent, 04.67.33.83.55, l-vincent@chu-montpellier.fr
- Not yet recruiting
CHRU Nancy - Hôpitaux de Brabois
Nancy, 54500
Caroline JACQUET, Dr., 03 83 15 72 95 ext. +33, c.jacquet@chru-nancy.fr
- Not yet recruiting
CHRU Hôtel Dieu
Nantes
Cyrille Touzeau, Dr, 02 20 08 32 71 ext. +33, cyrille.touzeau@chu-nantes.fr
- Not yet recruiting
Hôpital Universitaire Necker Enfants Malades
Paris, 75015
Laurent FRENZEL, Dr., 01 44 49 52 92 ext. +33, laurent.frenzel@aphp.fr
- Not yet recruiting
Hôpital Saint Louis
Paris
Stéphanie Harel, Dr, 01 42 49 96 92 ext. +33, stephanie.harel@aphp.fr
- Not yet recruiting
CHU Poitiers - Pôle régional de Cancérologie
Poitiers
Franck Bridoux, Pr, 05 49 44 41 59 ext. +33, f.bridoux@chu-poitiers.fr
- Not yet recruiting
CHRU Hôpital de Pontchaillou
Rennes
Olivier Decaux, Pr, 0299284321, olivier.decaux@chu-rennes.fr
- Recruiting
Pôle IUCT Oncopole CHU
Toulouse
Antoine Huart, Dr, 05 61 32 30 29 ext. +33, huart.a@chu-toulouse.fr
About this study
Official title: A Phase 2, Open Label, Multicenter, Single-stage Study to Evaluate the Efficacy of Isatuximab Plus Pomalidomide and Dexamethasone (IPd), in Patients With AL Amyloidosis Not in VGPR or Better After Any Previous Therapy
This phase 2 study ain to evaluate the efficacy of Isatuximab plus Pomalidomide and Dexamethasone (IPd), in patients with AL amyloidosis not in VGPR or better after any previous therapy. It will enrolled 46 patients (34 in France and 12 in Australia) through 15 sites (11 in France and 4 in Australia).
Read the detailed description
Systemic AL amyloidosis is a rare disease caused by the deposition of misfolded monoclonal immunoglobulin free light chains (FLC) in various tissues and organs. It is usually associated with a clonal plasma cell dyscrasia with a low tumor burden. Treatment of AL amyloidosis relies mainly on chemotherapy aimed at suppressing the underlying plasma cell clone secreting monoclonal FLC.
The organ responses and the survival are greatly influenced by the degree of hematological response evaluated by the decrease in serum FLC that has been the principal endpoint in recent trials in AL amyloidosis. The goal of treatment is to reach at least a very good partial response (VGPR) defined as a difference between the involved FLC and the normal one below 40 mg/L.
Over the last 5 years, monoclonal antibodies (mAb) as daratumumab and Isatuximab (anti CD38 mAb) has emerged as a breakthrough targeted therapies for patients with multiple myeloma (MM).
CD38, is a type II transmembrane glycoprotein that functions both as a signal-transducing receptor and a multifunctional ectoenzyme. The expression of CD38 is increased in MM and AL amyloidosis plasma cells.
Daratumumab (DARA) is an IgG 1k human mAb that received initial approval as monotherapy in patients with heavily pretreated RRMM and who were refractory to proteasome inhibitors (PIs) and immunomodulatory drugs (IMiD®). DARA has since been approved in combination with Lenalidomide/Dexamethasone1,2 and Bortezomib/Dexamethasone3,4 for the treatment of frontline and relapsed/refractory (RR) MM patients.
IFM and other groups previously demonstrated that DARA in monotherapy is safe and effective in relapsed AL amyloidosis patients5. Our prospective phase II study showed that about 70 to 80% of patients have a response but only around 50% reached a VGPR.
DARA activity could be increased with IMiD® as treating plasma cells with IMiD®, such as pomalidomide or lenalidomide, has been shown to increase the expression of CD38 levels on the surface of these cells.
In AL amyloidosis, the Italian and the British groups demonstrated that pomalidomide is very effective and better tolerated than lenalidomide especially in patients with renal insufficiency6,7. The dose of pomalidomide (4 mg) was like the dose used in MM.
Combining an anti CD38 mAb to pomalidomide could therefore be an attractive regimen for relapsed AL amyloidosis patients.
Isatuximab (ISA) is another IgG1 κ mAb that binds selectively to a unique epitope on the human CD38 receptor and has anti plasma cells activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of Isatuximab with Pomalidomide and low-dose Dexamethasone.
The addition of Isatuximab to Pomalidomide-Dexamethasone was used in a large phase III study in RRMM8. Safety profile was also favorable, and these results granted an approval of the combination of ISA plus Pomalidomide (4 mg) and Dexamethasone in these patients.
- Conditions
- AL Amyloidosis
- Being tested
- Isatuximab
- Keywords
- Amyloidosis, Isatuximab, Pomalidomide, Dexamethasone, Not in VGPR, Not in first line of treatment
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsatuximabDrug
Also called Pomalidomide, Dexamethasone
Patient will receive the association of Isatuximab, Pomalidomide and Dexamethasone during 9 or 12 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Single-stage | Experimental | Patient eligible to enter the study will receive 9 to 12 cycles (according to response) of intravenous Isatuximab (10 mg/kg) and oral Pomalidomide 4 mg from day 1 to day 21 and Dexamethasone 10-20 mg weekly on days 1, 8, 15 and 22.
Each cycle will be of 28 days duration. During cycle 1, Isatuximab will be administered weekly on days 1, 8, 15, and 22 then days 1 and 15 in subsequent cycles from cycle 2 to 9 or 12.
For each individual patient, the treatment period will be 12 months, unless CR at the completion of 9 cycles, disease progression or unacceptable toxicity occurs. The duration of follow-up for overall survival will be 1 year after the last patient enters overall survival follow-up. Receives: Drug: Isatuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematologic Response
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.
*: If iFLC <ULN and serum and urine immunofixation are negative, then neither a normal uFLC level nor a normal FLC ratio are required for complete response (CR).
Measured: At the end of Cycle 6 (each cycle is 28 days)
Secondary outcomes (11)
Overall Hematologic Response Rate
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.
*: If iFLC <ULN and serum and urine immunofixation are negative, then neither a normal uFLC level nor a normal FLC ratio are required for complete response (CR).
Measured: At the completion of the 1st, 2nd, 4th, 6th, 9th and 12th cycles (each cycle is 28 days)
Efficacy Measurement: Progression-free survival (PFS)
Time from the inclusion to either progressive disease or death
Measured: During the intervention and at 1 year
Efficacy Measurement: relapse-free survival (RFS)
To evaluate the relapse-free survival (RFS)
Measured: During the intervention
Efficacy Measurement: Organ response rate (OrRR)
To evaluate the Organ response rate at 1 year
Measured: 1 year
Efficacy Measurement: Overall Survival (OS)
Time from initial inclusion to death
Measured: Though study completion, an average of 33 months
Time to and the duration of haematologic and organ responses
To evaluate the time to and the duration of haematologic and organ responses
Measured: During the intervention
Safety analysis
Rate of adverse events that occured during treatment period
Measured: Until 30 days post last dose of protocol treatment
Cytogenetic: incidence of genetic translocation t(11;14) and impact on hematologic and organ response
To assess the impact of t(11.14) determined by Fluorescence In Situ Hybridation (FISH) at inclusion on treatment response.
Measured: Though study completion, an average of 33 months
Cardiac function
To assess the concentration of NT-proBNP level and evaluate the impact of the NT-proBNP level on the strain change.
Measured: After 6 cycles of IsaPd and at 1 year from start of therapy or 12 cycles of IsaPd (each cycle is 28 days).
Renal function
To assess albumin level to proteinuria/eGFR.
Measured: After 6 cycles of IsaPd and at 1 year from start of therapy or 12 cycles of IsaPd (each cycle is 28 days)
Quality of Life : European Quality of Life 5 dimensions (EQ-5D-3L)
patient reported outcome to assess health status in patients. The EQ-5D (European Quality of Life 3 dimensions) measures a wide range of health conditions and treatments; it is composed of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and a visual analogue scale that records the patient's self-rated overall health state.
Respondents rate each of these 5 dimensions from "no problem", "some problem" or "extreme problem".
The EQ-VAS records the respondents' self-related health on a vertical, visual analogue scale. The range for EQ-VAS is from 0 (the worst health you can imagine) to 100 (=the best healt you can imagine).
Measured: up to 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2021
- Study start11 Feb 2022
- Primary completionMar 2026 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AL AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Intergroupe Francophone du Myelome
- Sponsor type
- Research network
- Collaborators
- Sanofi, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Arnaud JACCARD, Pr, Principal investigator, CHU Limoges
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05066607
- Sponsor's protocol ID
- IFM 2020-01
- Acronym
- IsAMYP
- Status last verified
- Mar 2024
- First submitted
- 24 Aug 2021
- Last updated
- 6 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open Label, Multicenter, Single-stage Study to Evaluate the Efficacy of Isatuximab Plus Pomalidomide and Dexamethasone (IPd), in Patients With AL Amyloidosis Not in VGPR or Better After Any Previous Therapy
- ClinicalTrials.gov ID
- NCT05066607
- Acronym / sponsor ID
- IsAMYP / IFM 2020-01
- Conditions
- AL Amyloidosis
- Keywords
- Amyloidosis, Isatuximab, Pomalidomide, Dexamethasone, Not in VGPR, Not in first line of treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Intergroupe Francophone du MyelomeResearch network
- Collaborators
- Sanofi, Bristol-Myers Squibb
- Study start
- 11 Feb 2022 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 4 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 2 study ain to evaluate the efficacy of Isatuximab plus Pomalidomide and Dexamethasone (IPd), in patients with AL amyloidosis not in VGPR or better after any previous therapy. It will enrolled 46 patients (34 in France and 12 in Australia) through 15 sites (11 in France and 4 in Australia).
Detailed description
Systemic AL amyloidosis is a rare disease caused by the deposition of misfolded monoclonal immunoglobulin free light chains (FLC) in various tissues and organs. It is usually associated with a clonal plasma cell dyscrasia with a low tumor burden. Treatment of AL amyloidosis relies mainly on chemotherapy aimed at suppressing the underlying plasma cell clone secreting monoclonal FLC.
The organ responses and the survival are greatly influenced by the degree of hematological response evaluated by the decrease in serum FLC that has been the principal endpoint in recent trials in AL amyloidosis. The goal of treatment is to reach at least a very good partial response (VGPR) defined as a difference between the involved FLC and the normal one below 40 mg/L.
Over the last 5 years, monoclonal antibodies (mAb) as daratumumab and Isatuximab (anti CD38 mAb) has emerged as a breakthrough targeted therapies for patients with multiple myeloma (MM).
CD38, is a type II transmembrane glycoprotein that functions both as a signal-transducing receptor and a multifunctional ectoenzyme. The expression of CD38 is increased in MM and AL amyloidosis plasma cells.
Daratumumab (DARA) is an IgG 1k human mAb that received initial approval as monotherapy in patients with heavily pretreated RRMM and who were refractory to proteasome inhibitors (PIs) and immunomodulatory drugs (IMiD®). DARA has since been approved in combination with Lenalidomide/Dexamethasone1,2 and Bortezomib/Dexamethasone3,4 for the treatment of frontline and relapsed/refractory (RR) MM patients.
IFM and other groups previously demonstrated that DARA in monotherapy is safe and effective in relapsed AL amyloidosis patients5. Our prospective phase II study showed that about 70 to 80% of patients have a response but only around 50% reached a VGPR.
DARA activity could be increased with IMiD® as treating plasma cells with IMiD®, such as pomalidomide or lenalidomide, has been shown to increase the expression of CD38 levels on the surface of these cells.
In AL amyloidosis, the Italian and the British groups demonstrated that pomalidomide is very effective and better tolerated than lenalidomide especially in patients with renal insufficiency6,7. The dose of pomalidomide (4 mg) was like the dose used in MM.
Combining an anti CD38 mAb to pomalidomide could therefore be an attractive regimen for relapsed AL amyloidosis patients.
Isatuximab (ISA) is another IgG1 κ mAb that binds selectively to a unique epitope on the human CD38 receptor and has anti plasma cells activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of Isatuximab with Pomalidomide and low-dose Dexamethasone.
The addition of Isatuximab to Pomalidomide-Dexamethasone was used in a large phase III study in RRMM8. Safety profile was also favorable, and these results granted an approval of the combination of ISA plus Pomalidomide (4 mg) and Dexamethasone in these patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single-stage | Experimental | Drug: IsatuximabPatient eligible to enter the study will receive 9 to 12 cycles (according to response) of intravenous Isatuximab (10 mg/kg) and oral Pomalidomide 4 mg from day 1 to day 21 and Dexamethasone 10-20 mg weekly on days 1, 8, 15 and 22. Each cycle will be of 28 days duration. During cycle 1, Isatuximab will be administered weekly on days 1, 8, 15, and 22 then days 1 and 15 in subsequent cycles from cycle 2 to 9 or 12. For each individual patient, the treatment period will be 12 months, unless CR at the completion of 9 cycles, disease progression or unacceptable toxicity occurs. The duration of follow-up for overall survival will be 1 year after the last patient enters overall survival follow-up. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Age ≥ 18
- Histologic diagnosis of AL amyloidosis;
- Patients should have received at least one line with an alkylating agent and/or a PI, 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);
- Measurable hematologic disease: difference between involved and uninvolved FLC > 50 mg/L with an abnormal k/l ratio;
- Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system) (See Appendix 1);
Key exclusion criteria (30 listed)
- Presence of non-AL amyloidosis
- AL amyloidosis with isolated soft tissue involvement
- Bone marrow plasma cells >30% and clinically symptomatic multiple myeloma with lytic bone lesions
- NT-proBNP > 8500 ng/L and hs-troponin I > 100 ng/L or hs-troponin T > 50 ng/L (cardiac stage IIIb patients)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsatuximabAlso: Pomalidomide, DexamethasonePatient will receive the association of Isatuximab, Pomalidomide and Dexamethasone during 9 or 12 cycles. | Drug | Single-stage |
Primary outcome
Hematologic Response
Time frame: At the end of Cycle 6 (each cycle is 28 days)
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. *: If iFLC <ULN and serum and urine immunofixation are negative, then neither a normal uFLC level nor a normal FLC ratio are required for complete response (CR).
11 secondary outcomes
Overall Hematologic Response Rate
Time frame: At the completion of the 1st, 2nd, 4th, 6th, 9th and 12th cycles (each cycle is 28 days)
Efficacy Measurement: Progression-free survival (PFS)
Time frame: During the intervention and at 1 year
Efficacy Measurement: relapse-free survival (RFS)
Time frame: During the intervention
Efficacy Measurement: Organ response rate (OrRR)
Time frame: 1 year
Efficacy Measurement: Overall Survival (OS)
Time frame: Though study completion, an average of 33 months
Time to and the duration of haematologic and organ responses
Time frame: During the intervention
Safety analysis
Time frame: Until 30 days post last dose of protocol treatment
Cytogenetic: incidence of genetic translocation t(11;14) and impact on hematologic and organ response
Time frame: Though study completion, an average of 33 months
Cardiac function
Time frame: After 6 cycles of IsaPd and at 1 year from start of therapy or 12 cycles of IsaPd (each cycle is 28 days).
Renal function
Time frame: After 6 cycles of IsaPd and at 1 year from start of therapy or 12 cycles of IsaPd (each cycle is 28 days)
Quality of Life : European Quality of Life 5 dimensions (EQ-5D-3L)
Time frame: up to 15 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arnaud JACCARD, Pr principal investigator
CHU Limoges
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isatuximab in people with AL Amyloidosis, run by Intergroupe Francophone du Myelome at 15 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cécile DEAL (01 40 21 24 01 ext. +33, c.deal@myelome.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hematologic Response (time frame: At the end of Cycle 6 (each cycle is 28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2024.