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Gene-Modified Stem Cell Therapy for Subjects With Transfusion-dependent Beta-thalassemia

ConditionTransfusion-dependent Beta-Thalassemia
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age3-35
SponsorFondazione Telethon

About this trial

This is a prospective, dual-centre, single dose, Phase IIb, single arm, open label study. The proposed clinical trial involves a single infusion of autologous HSPCs genetically modified with the GLOBE lentiviral vector, using an improved transduction protocol in 9 patients affected by transfusion dependent Beta-Thalassemia.

Four study phases are foreseen:

1. Screening phase, during which the conditions required by the clinical protocol for patients' inclusion/exclusion will be assessed after the signature of the informed consents/assents. Patients will be recruited from the two participating sites: IRCCS Ospedale San Raffaele (OSR), Department of Pediatric Immunohematology and adult Hematology (OSR Stem Cells Programme) (Milan) and IRCCS Ospedale Pediatrico Bambino Gesù (OPBG), Department of Haematology, Oncology and Gene and Cell Therapy (Rome). 2. Baseline phase, carried from the end of the screening phase to the day before the start of the conditioning regimen. 3. Treatment phase, from the first day of conditioning regimen until DP administration. 4. Follow-up phase: from DP administration until 2 years follow-up.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Must be willing to adhere to the protocol as evidenced by written informed consent for adults or parental informed consent and subject assent for adolescents and children.

Male and female adults/adolescents/children diagnosed with transfusion-dependent β-thalassemia (homozygous or compound heterozygous). At least 2 out of the 9 patients must have B0/B0 or B0/B0-like genotype. In case the genetic diagnosis available at screening wasn't performed in a certified laboratory (check under PI's or delegated investigator's responsibility), the genetic diagnosis will be repeated at clinical sites during the screening phase.

Documented history of at least 100 ml/kg/year or 10 U/year of packed red blood cell transfusions in each of the 2 years prior to signing informed consent.

Age ≥ 18 years and ≤ 35 years for Group 1, Age ≥ 3 years and ≤ 35 years for Group 2.

Disqualifiers

Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents).

Severe, active viral, bacterial or fungal infection at eligibility evaluation.

Current or prior malignant neoplasia (except local skin cancer or cervical intraepithelial neoplasia) or exceptional family history of familial cancer syndromes.

Current or prior immunodeficiency disorder.

Trial design

Design model

Single group

Treatments tested in this trial

  • FT007

    Genetic

    Autologous hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with the lentiviral vector GLOBE encoding for the human beta globin using an improved transduction protocol, re-suspended in their final formulation medium and cryopreserved.

Treatment groups

9 Participants
are divided into 1 treatment group
Group A: subjects with transfusion-dependent beta-thalassemiaExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Proportion of subjects who achieve TI12 in the 2 years from DP administration

Proportion of Subjects achieving transfusion independence defined as a weighted average Hb ≥ 9.0 gr/dL without any red blood cell transfusion for a continuous period of ≥ 12 months (TI12) at any time during the study after the drug product administration The assessment of TI12 starts 60 days after last RBC transfusion for post-transplant support or BTHAL standard of care.

Time frame
from 60 days after the IMP infusion, to 24 months of follow-up

Secondary outcomes

1

Overall survival

Overall survival at 12 and 24 months post IMP infusion

Time frame
12 months and 24 months post IMP infusion
2

Proportion of Subjects who achieve hematological engraftment ≤ day +60 from DP administration

Proportion of Subjects who achieve hematological engraftment ≤ day +60 from DP administration defined as first day of absolute neutrophil count ≥ 0.5 x 10\^9/L on 3 consecutive measurements obtained on different days and platelets ≥20x 10\^9/L in the absence of platelet transfusions and/or growth factor support for at least 7 consecutive days.

Time frame
from Day 11 to Day 60 post IMP infusion
3

Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) (Safety and tolerability of the administration of FT007)

Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) attributed to procedures related to harvesting of HSPCs, conditioning regimen, FT007 administration (from screening to 24 months post GT).

Time frame
from Baseline to 24 months post IMP infusion
4

Proportion of Subjects with abnormal clonal proliferation development due to insertional mutagenesis

Proportion of Subjects with abnormal clonal proliferation development due to insertional mutagenesis

Time frame
6, 12, 18 and 24 months post IMP infusion

Other outcomes

Sponsors and contacts

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Fondazione Telethon

Lead sponsor

Ospedale San Raffaele

Collaborator

Source ClinicalTrials.gov
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