ISKPD-IFM2018-03-Multicenter Open label Phase 2 study of Isatuximab plus Pomalidomide and Dexamethasone with Carfilzomib in Relapsed or Refractory Multiple Myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Poitiers

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

15 Sep 2020 → 26 Sep 2025

Decision date (initial)

2024-08-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

CHU de Poitiers

External identifiers

EU CT number

2024-516670-29-00

EudraCT number

2019-001027-12

ClinicalTrials.gov

NCT04287855

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Dose response

The primary objective is to determine the efficacy of IsPd + K in early Relapse Refractory Multiple Myeloma according to IMWG*.

Secondary objectives 3

1. To assess the safety according to CTCAE 5.0.
2. To assess response to the treatment according to IMWG*
3. To assess the survival according to IMWG

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1)Must be able to understand and voluntarily sign an informed consent form
2. 2)Must be able to adhere to the study visit schedule and other protocol requirements
3. 3)Male or female, age 18 years or older
4. 4)Life expectancy of > 6 months.
5. 5) Must be in R1 (Line 2) and R2 (Line 3) relapse Multiple Myeloma with a measurable disease o Have had 1 to maximum 2 lines of therapy prior to study entry o Relapse Refractory or primary refractory or relapse o Must have received prior treatment with a Lenalidomide-containing regimen for at least 2 consecutive cycles
6. 6) Must have measurable disease as defined by the following: must have a clearly detectable and quantifiable monoclonal M-component value in the serum and/or urine. o IgG/IgA (serum M-component > 5g/l), o Light chain (serum M-component >1g/l or Bence Jones > 200mg/24H), o Serum FLC assay (including for IgD isotypes): involved FLC level > 10 mg/dl provided serum. FLC ratio is abnormal for patients not measurable on any of the 3 above criteria.
7. 7) Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
8. 8) Wash out period without MM treatment must be of 28 days minimum before C1D1, except for anti CD-38 (See exclusion criteria#10).
9. 9) Adequate bone marrow function, documented within 72 hours and without transfusion 72 hours prior to the first intake of investigational product (C1J1) with no growth factor support (one week), defined as: o Absolute neutrophils ≥ 1 x109/L, o Untransfused Platelet count ≥ 75 x109/L, o Hemoglobin ≥ 8.5 g/dL.
10. 10) Adequate organ function defined as: o Serum total bilirubin < 2x upper limit of normal (ULN), o Clearance creatinine ≥ 30ml/min, o Serum SGOT/AST or SGPT/ALT < 3x upper limit of normal (ULN).
11. 11) Patients affiliated to an appropriate social security system.
12. 12) A man who is sexually active with a pregnant female or a FCBP* must agree to use a barrier method of birth control eg, condom with spermicidal foam/gel/film/cream/suppository, even if he has had a vasectomy. All men must also not donate sperm, spermatozoa during the study, for 5 months following treatment discontinuation.
13. 13) A woman FCBP* must understand and agree to use 2 reliable effective methods (a very effective method and an effective additional method) of contraception simultaneously without interruption: o For at least 28 days before starting experimental treatments o Throughout the entire duration of experimental treatments, o During dose interruptions, o And for at least 5 months after the last dose of experimental treatments.
14. 14) All patients must agree to not donate blood during the treatment period, interruptions of treatment and at least 5 months after the last dose of treatment
15. 15) All patients must understand and accept to comply with the conditions of the Pomalidomide pregnancy prevention plan (Appendix of the protocol).

Exclusion criteria 20

1. 1) Any other uncontrolled medical condition or comorbidity that might interfere with subject’s participation, including simultaneous participation to another interventional clinical study.
2. 2) Known positive for HIV or active infectious hepatitis, type B or C.
3. 3) Patients with non-secretory MM and non-measurable MM
4. 4) Patient with terminal renal failure that require dialysis or clearance creatinine < 30 ml/min (calculated with MDRD formula)
5. 5) Any uncontrolled or severe cardiovascular or pulmonary disease determined by the investigator including: o NYHA functional classification III or IV congestive heart failure o LVEF (Left Ventricular Ejection Fraction) < 40% o Uncontrolled angina, hypertension or arrhythmia o Myocardial infarction in the past 6 months
6. 6) Prior history of malignancies, other than multiple myeloma, unless the patients has been free of the disease for ≥ 5 years. Exceptions include the following: o Basal or squamous cell carcinoma of the skin o Carcinoma in situ of the cervix or breast o Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
7. Evidence of central nervous system (CNS) involvement
8. 8) Ongoing active infection or other clinically significant uncontrolled cardiovascular events
9. 9) Unable to comply with IMids regulation to thromboprophylaxis, or teratogenic recommendations.
10. 10) Refractory to prior anti CD38. Patients can be exposed to anti CD38 (any), BUT the wash out period for patient pre-treated with an anti CD38 antibody must be of 4,5 months minimum between last dose of previous anti-CD38 antibody and the first dose of isatuximab.
11. 11) Refractory to prior carfilzomib.
12. 12) Known allergy to one of the study product (pomalidomide, isatuximab, carfilzomib) or dexamethasone
13. Patient with a history of severe allergic reactions to thalidomide or lenalidomide
14. Previously exposed to pomalidomide
15. Known intolerance to infused protein products, sucrose, histidine, and polysorbate 80
16. Contraindications to dexamethasone
17. Any ongoing non hematological adverse event grade > 2 severity or medical history grade > 2 severity
18. 18) Pregnant or breast-feeding females
19. Refusal to participate in the study
20. Persons protected by a legal regime (guardianship, trusteeship)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MRD 10-5 incidence rate determined (as the best response obtained at any time point during treatment) as per IMWG criteria by NGS (centrally performed, Pr Avet Loiseau Toulouse Oncopole).

Secondary endpoints 4

1. Treatment emergent adverse events of IsPd +K will be evaluated according to CTCAE 5.0.
2. To determine Overall Response Rate (ORR, Partial Response and better), Very Good Partial Response (VGPR) + CR rate of IsPd +K as per IMWG criteria and with M protein interference testing. Clinical benefit response rate (CBR, Minor Response (MR) and better) of IsPd +K as per IMWG criteria.
3. Time to response and Response duration for responders as per IMWG criteria.
4. Overall Survival (OS), Progression free survival (PFS), Time To Progression (TTP), Time To Next Therapy (TTNT) and Event Free survival (EFS) of IsPd +K will be evaluated as per IMWG criteria.

Investigational products

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

Test 6

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Poitiers

Sponsor organisation

Centre Hospitalier Universitaire De Poitiers

Address

2 Rue De La Miletrie

City

Poitiers

Postcode

86000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Poitiers

Contact name

Coordinating investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Poitiers

Contact name

Coordinating investigator

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 9 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