Isatuximab Plus Pomalidomide and Dexamethasone Association for Patients With AL Amyloidosis Not in VGPR or Better After Any Previous Therapy

NCT05066607 | Recruiting Phase 2 DMC

• 1 other identifier: IFM 2020-01
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 15

Brief 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).

Conditions

AL Amyloidosis

Keywords

Amyloidosis; Isatuximab; Pomalidomide; Dexamethasone; Not in VGPR; Not in first line of treatment

Outcome Measures

Primary Outcomes (1)

• 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).

  At the end of Cycle 6 (each cycle is 28 days)

Secondary Outcomes (11)

• Overall Hematologic Response Rate

  At the completion of the 1st, 2nd, 4th, 6th, 9th and 12th cycles (each cycle is 28 days)

• Efficacy Measurement: Progression-free survival (PFS)

  During the intervention and at 1 year

• Efficacy Measurement: relapse-free survival (RFS)

  During the intervention

• Efficacy Measurement: Organ response rate (OrRR)

  1 year

• Efficacy Measurement: Overall Survival (OS)

  Though study completion, an average of 33 months

Other Outcomes (1)

• Minimal Residual Disease (MRD)

  At the completion of 6 cycles of therapy or at 1 year from start of therapy (each cycle is 28 days)

Study Arms (1)

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.

Drug: Isatuximab

Interventions

Isatuximab DRUG

Patient will receive the association of Isatuximab, Pomalidomide and Dexamethasone during 9 or 12 cycles.

Also known as: Pomalidomide, Dexamethasone

Single-stage

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18
• Histologic diagnosis of AL amyloidosis;
• 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.
• 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,

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Intergroupe Francophone du Myelome: lead
• Sanofi: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (15)

CHU Amiens-Picardie

Amiens, 80054, France

NOT YET RECRUITING

CHRU - Hôpital du Bocage

Angers, France

NOT YET RECRUITING

CHU Caen - Côte de Nacre

Caen, France

NOT YET RECRUITING

Groupe Hospitalier Mutualiste de Grenoble

Grenoble, 38028, France

NOT YET RECRUITING

CHRU Hôpital Claude Huriez

Lille, France

NOT YET RECRUITING

Centre Hospitalier Universitaire (CHU) de Limoges

Limoges, France

NOT YET RECRUITING

Centre Hospitalier Lyon Sud

Lyon, France

NOT YET RECRUITING

Hopital Saint Eloi - CHU Montpellier

Montpellier, France

NOT YET RECRUITING

CHRU Nancy - Hôpitaux de Brabois

Nancy, 54500, France

NOT YET RECRUITING

CHRU Hôtel Dieu

Nantes, France

NOT YET RECRUITING

Hôpital Universitaire Necker Enfants Malades

Paris, 75015, France

NOT YET RECRUITING

Hôpital Saint Louis

Paris, France

NOT YET RECRUITING

CHU Poitiers - Pôle régional de Cancérologie

Poitiers, France

NOT YET RECRUITING

CHRU Hôpital de Pontchaillou

Rennes, France

NOT YET RECRUITING

Pôle IUCT Oncopole CHU

Toulouse, France

RECRUITING

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Amyloidosis

Interventions

isatuximab; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Arnaud JACCARD, Pr

  CHU Limoges

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cécile DEAL

CONTACT

01 40 21 24 01; c.deal@myelome.fr

Léa TABONE

CONTACT

01 40 21 24 04; l.tabone@myelome.fr

Study Design

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

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: October 4, 2021
• Study Start: February 11, 2022
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: March 6, 2024

Record last verified: 2024-03

Locations

FR (15)