An open, randomised, controlled phase II trial of CellProtect in combination with Isatuximab antibody versus Isatuximab antibody alone as maintenance treatment in patients with Multiple Myeloma undergoing high dose treatment (ISA-HC-NK)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska Institutet, Karolinska Institutet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

28 Jul 2023 → ongoing

Decision date (initial)

2024-09-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514527-42-00

EudraCT number

2020-000994-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To demonstrate the benefit of Isatuximab (ISA) in combination with CellProtect in the enhancement of overall response rate (ORR) as compared to Isatuximab in patients with newly diagnosed multiple myeloma (NDMM) eligible for autologous stem cell transplantation (ASCT) as maintenance treatment after high dose treatment (HDT).

Secondary objectives 2

1. To evaluate efficacy of Isatuximab (ISA) in combination with CellProtect as compared to Isatuximab
2. To evaluate safety and tolerability of Isatuximab (ISA) in combination with CellProtect as compared to Isatuximab

Conditions and MedDRA coding

Multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Active multiple myeloma, as defined by the IMWG criteria
2. Evidence of measurable disease: Serum monoclonal (M)-protein ≥1.0 g/dL measured using serum protein immunoelectrophoresis a. and/or
3. Urine M-protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis a. and/or
4. In patients without measurable M protein in serum or urine as per previous criteria, serum immunoglobulin free light chain (sFLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio <0.26 or >1.65.
5. Patients who are newly diagnosed and considered for high-dose chemotherapy
6. Patient has given voluntary written informed consent before performance of any study related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his/her medical care.
7. ≥18 years of age (and satisfying the legal age of consent in the jurisdiction in which the study is taking place)
8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
9. Male or Female: Male participants a. A male participant must agree to use contraception specified in this protocol during the intervention period and for at least 5 months after the last dose of study treatment and refrain from donating sperm during this period
10. Male of female: Female participants A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a Females of childbearing potential (FCBP)
11. Screening #2 (Conducted after HDT): Inclusion criteria I7-I10 in addition to response evaluation (at least partial remission must be met)

Exclusion criteria 24

1. Prior or concurrent exposure to NK cells and NK like T cells, or Approved or investigational treatments for MM
2. Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer
3. Diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage)
4. Diagnosis of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
5. Prior or current systemic therapy, or SCT for symptomatic multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids, if completed within 14 days prior to randomization
6. Concomitant plasma cell leukemia
7. Any major procedure within 14 days before the initiation of the study treatment: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy (except if palliative intent)
8. ECOG PS >2
9. Hemoglobin <8 g/dL
10. Platelets <70 × 109/L if <50% of bone marrow (BM) nucleated cells are plasma cells, and ≤30 × 109/L if ≥50% of BM nucleated cells are plasma cells. Platelet transfusion is not allowed within 3 days before the screening haematological test
11. Total bilirubin >1.5 × upper limit of normal (ULN), except for known Gilbert syndrome
12. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 × ULN
13. Hypersensitivity (or contraindication) to dexamethasone, sucrose histidine (as base and hydrochloride salt), boron, mannitol, and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids, pregelatinized starch, sodium stearyl fumarate, arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents
14. Second/third degree heart block within 6 months prior to randomization
15. Poorly controlled hypertension within 6 months prior to randomization
16. Myocardial infarction within 6 months prior to randomization
17. Severe/unstable angina pectoris within 6 months prior to randomization
18. Coronary/peripheral artery bypass graft within 6 months prior to randomization
19. New York Heart Association class III or IV congestive heart failure within 6 months prior to randomization
20. Grade ≥3 arrhythmias within 6 months prior to randomization
21. Stroke or transient ischemic attack within 6 months prior to randomization
22. Left-ventricular ejection fraction <40% within 6 months prior to randomization
23. Prior malignancy. Adequately treated basal cell or squamous cell skin, or superficial (pTis, pTa, and pT1) bladder cancer, or low risk prostate cancer, or any in situ malignancy after curative therapy are allowed, as well as any other cancer for which cytotoxic chemotherapy has been completed ≥3 years prior to enrolment and from which the patient has been disease-free for ≥3 years
24. Known acquired immunodeficiency syndrome (AIDS)-related illness or known HIV disease requiring antiviral treatment or active hepatitis A (defined as positive HA antigen), B (defined as either positive HBs antigen or negative HBs antigen with positive HBc antibody), or C infection (defined as a known positive hepatitis C antibody result and known quantitative hepatitis C (HCV) ribonucleic acid (RNA) results greater than the lower limits of detection of the assay)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Enhancement of ORR (yes/no), defined as “yes” for patients that show an increase in ORR at Visit 15 (start of cycle 4) as compared to Visit 2 (baseline), and “no” otherwise.

Secondary endpoints 7

1. Overall Response Rate (ORR, scores 1-7) defined as the highest class fulfilled by the patient at one time point: 1. PD, 2. SD or MR (SD, not fulfilling PD, MR, PR, VGPR or CR, or Minimal Response, ≥ 25% reduction in serum M-protein), 3.PR ≥ 50% reduction in serum M-protein, 4. VGPR ≥ 90% reduction in serum M-protein, 5. CR (Serum immunofixation not measurable), 6. Flow MRD negative, 7. Sustained MRD negative (compared to Visit 2)
2. Treatment-emergent adverse events/serious adverse events (TEAEs/SAEs) (including IARs)
3. Laboratory parameters
4. Vital signs
5. Weight
6. ECOG PS
7. Findings from physical examination

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska Institutet

Sponsor organisation

Karolinska Institutet

Address

Nobels Vag 6

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

Karolinska Institutet

Contact name

Eva Hellström Lindberg

Public contact point

Organisation

Karolinska Institutet

Contact name

Eva Hellström Lindberg

Karolinska Institutet

Sponsor organisation

Karolinska Institutet

Address

Alfred Nobels Alle 8, Flemingsberg Flemingsberg

City

Huddinge

Postcode

141 52

Country

Sweden

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 4 files

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

Application history

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