A Phase I/II Study Evaluating Temferon in Multiple Myeloma Patients With Early Relapse After Front Line Therapy (TEM-MM)

NCT03875495 | Terminated Phase 1 Results DMC

• 1 other identifier: TEM-MM-101
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, open label, phase I/II, dose-escalation study, involving a single injection of Temferon, an investigational advanced therapy consisting of autologous CD34+-enriched hematopoietic stem and progenitor cells exposed to transduction with a lentiviral vector driving myeloid-specific interferon-ɑ2 expression, which will be administered to up to 9 patients affected by multiple myeloma in early relapse after intensive front line treatment.

Conditions

Multiple Myeloma

Keywords

Temferon; Gene Therapy; Immunotherapy; Hematological malignancy

Outcome Measures

Primary Outcomes (1)

• Tolerability and Safety of Temferon Over the First 90 Days Following Administration as Determined by the Incidence of CTCAEs

  0 participants analyzed. All the patients were withdrawn before treatment

  90 days

Secondary Outcomes (14)

• Long Term Tolerability and Safety of Temferon as Determined by the Incidence of CTCAEs

  2 years

• Proportion of Patients Achieving Hematologic Recovery by Day +30 (Defined as the First of at Least 3 Consecutive Days With a Neutrophil Count >0.5 x 10^9/L and Platelet Count >20 x 10^9/L) in the Absence of Transfusions

  30 days

• Determine the Maximum Tolerated Dose of Temferon

  30 days

• Identify Presence of Transduced Myeloid Cells in Bone Marrow as Determined by Vector Copy Number

  Up to 2 years

• Identify Presence of Transduced Myeloid Cells in Peripheral Blood as Determined by Vector Copy Number

  Up to 2 years

Study Arms (1)

Temferon

EXPERIMENTAL

Autologous CD34+-enriched hematopoietic progenitor cells exposed ex vivo to a specific lentiviral vector encoding for the human IFN-ɑ2 gene. Its expression is tightly controlled by the human TIE2 enhancer/promoter sequence and by a post-transcriptional regulation layer represented by target miRNA sequences. This enables suppression of IFN-ɑ2 expression in HSPCs, thereby further increasing the specificity of the delivery strategy for their Tie2 expressing myeloid cell progeny.

Drug: Temferon

Interventions

Temferon DRUG

Genetically modified autologous HSPCs

Temferon

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Multiple myeloma patients with early relapse after intensive front-line treatment and disease measurable by serum biomarkers, who have obtained at least a VGPR after second-line salvage treatment.
• Able and willing to provide written informed consent.
• Able to comply with study protocol and procedures.
• Performance status scores: Eastern Cooperative Oncology Group (ECOG) \< 2 and Karnofsky \> 70%.
• Life expectancy of ≥ 6 months.
• Adequate cardiac, renal, hepatic and pulmonary functions as evidenced by (at screening and prior to conditioning):
• Left ventricular ejection fraction (LVEF) ≥ 45% by echo and normal electrocardiogram (ECG) or presence of abnormalities not significant for cardiac disease. Absence of severe pulmonary hypertension;
• Diffusing capacity of the lung for carbon monoxide (DLCO) \>50% and forced expiratory volume in 1 sec (FEV1) and forced expiratory vital capacity (FVC) \> 60% predicted (if non cooperative: pulse oximetry \> 95 % in room air);
• Serum creatinine \< 2x ULN and estimated glomerular filtration rate (eGFR) \> 30 ml/min/1.73m2;
• Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 x ULN, and total bilirubin ≤ 2.0 mg/dl.
• Women of child-bearing potential enrolled in the study must have a negative pregnancy test at screening and agree to use two distinct acceptable methods of contraception during the trial.
• Men enrolled in the study with partners who are women of child bearing potential, must be willing to use an acceptable barrier contraceptive method during the trial or have undergone successful vasectomy at least 6 months prior to entry into the study. Successful vasectomy needs to have been confirmed by semen analysis.

You may not qualify if:

• Use of other investigational agents within 4 weeks prior to experimental treatment (within 6 weeks if use of long-acting agents).
• Severe active viral, bacterial, or fungal infection at eligibility evaluation.
• Active autoimmune disease or a clinically relevant autoimmune manifestations, requiring immunosuppressive treatment, i.e. psoriasis, systemic lupus erythematosus, rheumatoid arthritis, vasculitis, immune-mediated peripheral neuropathies.
• Active sarcoidosis requiring steroid or other immunosuppressive treatment.
• Primary amyloidosis.
• History of neuropsychiatric illness including severe depression, schizophrenia, bipolar disorders, impaired cognitive function, dementia or suicidal tendency.
• Neuropathy \> grade 2.
• History of severe cardiovascular disease such as prior stroke, coronary artery disease requiring intervention, unresolved arrhythmias.
• Malignant neoplasia (except local skin cancer or cervical intraepithelial neoplasia) or family history of familial cancer syndromes.
• Myelodysplasia, cytogenetic or molecular alterations specifically associated with clonal hematopoiesis of the myeloid lineage, or other serious hematological disorder other than the plasma cell dyscrasia.
• Other clinical conditions judged by the Investigator non-compatible with the study procedures.
• Positivity for HIV-1 or HIV-2 (serology or RNA), and/or Hepatitis B Virus Surface Antigen (HbsAg) and/or Hepatitis B Virus (HBV) DNA and/or Hepatitis C Virus (HCV) RNA (or negative HCV RNA but on antiviral treatment) and/or Treponema Pallidum or Mycoplasma active infection.
• Active alcohol or substance abuse within 6 months of the study.
• Pregnancy or lactation.
• Previous allogeneic bone marrow transplantation, kidney or liver transplant, or gene therapy.

Sponsors & Collaborators

• Genenta Science: lead
• IRCCS San Raffaele: collaborator

Study Sites (1)

Ospedale San Raffaele

Milan, 20132, Italy

Location

MeSH Terms

Conditions

Multiple Myeloma; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site

Limitations and Caveats

Although 3 patients were recruited, no patients received Temferon

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Genenta Science

info-trial@genenta.com

+39 02 2643 3982

Study Officials

• Fabio Ciceri, MD

  Ospedale San Raffaele, Milan, Italy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 14, 2019
• Study Start: March 6, 2019
• Primary Completion: April 2, 2021
• Study Completion: April 2, 2021
• Last Updated: January 28, 2022
• Results First Posted: January 28, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)