Early phase study to evaluate the safety and efficacy of SMART101 to improve transplantation in blood cancers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Smart Immune, Smart Immune

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Immune System Diseases [C20]

Trial duration

7 Jun 2023 → ongoing

Decision date (initial)

2024-11-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-517953-28-00

EudraCT number

2022-002530-14

ClinicalTrials.gov

NCT05768035

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Segment 1: To determine the SMART101 recommended dose (RecD)

Segment 2:
- Safety: To evaluate the safety of SMART101 in term of unacceptable toxicity in the SMART101 arm
- Efficacy: To evaluate the activity of SMART101 in term of CD4+ T-cell reconstitution

Secondary objectives 6

1. To assess the safety profile of SMART101
2. To determine the efficacy of SMART101 in improving immune reconstitution post-HSCT
3. To assess the efficacy of SMART101 in improving thymus function post HSCT
4. To assess the efficacy of SMART101 in preventing infections post-HSCT
5. To assess the efficacy of SMART101 in reducing non-relapse mortality (NRM) post-HSCT
6. To assess the efficacy of SMART101 in improving long-term outcomes post-HSCT

Conditions and MedDRA coding

Treatment in haematopoietic stem cell transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patients and Donors written informed consents. Patients must have voluntarily signed the written informed consent (ICF) before performance of any study-related inclusion procedures. Donors must have voluntarily signed the written ICF before the apheresis donation.
2. Patients with AML, ALL or MDS eligible for an allogeneic HSCT with a HLA-mismatched donor (haploidentical or 9/10 matched unrelated donor, MUD) with post-transplant cyclophosphamide. In case of ≥ 5% bone marrow blasts, the investigator must contact the Sponsor for review and final eligibility decision.
3. Patients must be ≥ 18 years of age at the time of signing the ICF
4. Patients must have a Karnofsky index ≥ 70%
5. Patients must have a left ventricular ejection fraction of ≥40%
6. Patients must have an intact pulmonary function or Diffusing capacity of the Lungs for Carbon Monoxide (DLCO) ≥ 45% of predicted
7. Patients must have adequate hepatic and renal functions, as assessed by standard laboratory criteria and defined as: Bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert’s Syndrome, hemolysis or transfusion dependence; AST and ALT ≤ 2.5 x ULN; Alkaline phosphatase < 5 x ULN; Serum creatinine < 1.5 × ULN or creatinine clearance ≥ 60 mL/min (Cockcroft and Gault) for serum creatinine ≥ 1.5x ULN
8. Women of childbearing potential must: have a negative pregnancy test; sexually active women must agree to use an effective method of birth control with their male partner (combined hormonal contraception or progesterone-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD) intrauterine hormone-releasing system (IUS) bilateral tubal occlusion, vasectomy or sexual abstinence) consistently and correctly for at least 1 year after the last administration of cyclophosphamide; agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction for at least 1 year after the last administration of cyclophosphamide; agree to no plan to breastfeed for at least 100 days after the infusion of SMART101 and no plan to become pregnant for at least 1 year after the last administration of cyclophosphamide
9. Males who are sexually active must: agree to use an effective method of birth control with their partner of childbearing potential (combined hormonal contraception or progesterone-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS) bilateral tubal occlusion, vasectomy or sexual abstinence) consistently and correctly for at least 6 months after the last administration of cyclophosphamide or 1 year after the last administration of Thiotepa if applicable; agree to not donate sperm for at least 6 months after the last administration of cyclophosphamide or 1 year after the last administration of Thiotepa if applicable; no plan to father a child within 6 months after the last administration of cyclophosphamide or 1 year after the last administration of Thiotepa if applicable

Exclusion criteria 12

1. Patients who have received prior allogeneic stem cell transplantation
2. Patients who have received prior treatment with another cellular therapy within 4 weeks before the planned day of SMART101 infusion
3. Patients who plan to receive, are concurrently receiving or have received any investigational agent within 4 weeks before the planned day of SMART101 infusion
4. Patients who have uncontrolled infection
5. Patients with a documented history of human immunodeficiency virus (HIV) or human T-cell leukemia virus type 1 (HTLV-1), diagnosed by antibody assays or found positive following the serology testing scheduled at screening
6. Patients with a documented Hepatitis B or hepatitis C infection with measurable viral load
7. Patients with a known liver cirrhosis
8. Patients with a confirmed tumor involvement in the central nervous system (CNS)
9. Patients with psychiatric/social situations or addictive disorders, including active alcohol, that may compromise the ability of the patients to give informed consent or to comply with the study procedures (according to the Investigator’s judgement)
10. Any abnormal condition or laboratory result that may alter patient’s condition or study outcome according to the Investigator’s judgement
11. Patients with a history of allergic reactions or hypersensitivity attributed to the excipients of SMART101 (dimethyl sulfoxide [DMSO])
12. Patients with a contraindication, including allergic reactions or hypersensitivity, to any medication as proposed per protocol or used as standard of care according to institutional standards of each participating stud site during the whole study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety (Segment 1 and Segment 2): Occurrence of Unexpected Unacceptable Toxicities (UUT) following the administration of SMART101, within 28 days post SMART101 infusion
2. Efficacy (Segment 2): T-cell reconstitution rate, defined as naïve CD4+ T cell count ≥ 50/μL within 100 days post-HSCT, confirmed on a subsequent measurement within 2 months

Secondary endpoints 10

1. Occurrence of all adverse events (AEs) and serious adverse events (SAEs), and specifically the occurrence of Adverse Event of Special Interest (AESI) related to the HSCT procedure following the administration of SMART101, defined as: Grade III-IV acute GvHD; Graft failure
2. T-cell reconstitution defined as the assessment of the different CD3+ TCRαβ+ cell subpopulations at D30, D60, D100, M4, M5, M6, M9 and M12: Naïve CD4+ and CD8+ populations; Memory T cells within the CD4 and CD8 T cell compartments; Activated T cells within the CD4 and CD8 T cell compartments; Regulatory T cells
3. B-cell reconstitution defined as the following parameters at D30, D60, D100, M4, M5, M6, M9 and M12: Number of B cells; Ig levels; Stop of intravenously IgG replacement therapy
4. NK cell reconstitution at D30, D60, D100, M4, M5, M6, M9 and M12
5. Analysis of the recent thymic emigrant (RTE) at D30, D60, D100, M4, M5, M6, M9 and M12
6. Analysis of T-cell receptor excision circle (TREC) at baseline (before conditioning), D60, D100, M4, M5, M6,M9 and M12
7. Imaging of the thymus with MRI at baseline (before conditioning) and M6
8. Cumulative incidence of infections at D100, M6 and M12
9. NRM cumulative incidence at D100, M6, M12 and M24
10. The following endpoints at D100, M6, M12 and M24: Relapse rate (RR); Event free survival (EFS); Disease-free survival (DFS); GvHD-free, relapse-free survival (GRFS); Overall survival (OS)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Smart Immune

Sponsor organisation

Smart Immune

Address

67 Rue De Seine

City

Paris

Postcode

75006

Country

France

Scientific contact point

Organisation

Smart Immune

Contact name

Clinical Development Department

Public contact point

Organisation

Smart Immune

Contact name

Clinical Development Department

Smart Immune

Sponsor organisation

Smart Immune

Address

67 Rue De Seine

City

Paris

Postcode

75006

Country

France

Locations

2 EU/EEA countries · 7 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 13 files

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

Application history

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