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Multiple MyelomaPhase 1/2NCT03875495

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

A Phase 1/2 study testing Temferon in people with Multiple Myeloma, run by Genenta Science at 1 site in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Multiple Myeloma
What is being tested?
Temferon
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteItaly
Study dates
6 Mar 2019to 2 Apr 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Prior to conditioning: inability to meet the target mobilization cell number needed to manufacture the Drug Product after at least 2 attempts of HSPC collection.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Ospedale San Raffaele

    Milan, 20132

Other trials in Italy

About this study

Official title: A Phase I/II Dose Escalation Study Evaluating Safety and Activity of Autologous CD34+-Enriched Hematopoietic Progenitor Cells Genetically Modified With a Lentiviral Vector Encoding for the Human Interferon-ɑ2 Gene in Multiple Myeloma Patients With Early Relapse After Intensive Front Line Therapy

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.

Read the detailed description

This is a non-randomized, open label, single center, phase I/II, therapeutic exploratory, dose-escalation, prospective study, involving a single intravenous infusion of Temferon, an investigational advanced therapy consisting of autologous CD34+-enriched hematopoietic stem and progenitor cells (HSPCs) exposed to transduction with a third-generation, vesicular stomatitis virus-G (VSV-G) pseudo-typed lentiviral vector driving myeloid-specific interferon-ɑ2 (IFN-ɑ2) expression, which will be administered to up to 9 patients affected by multiple myeloma in early relapse after intensive front line treatment. The study will recruit, treat and follow-up patients at a specialist hematology and bone marrow transplantation unit at Ospedale San Raffaele (OSR) in Milan, Italy.

The study will enrol multiple myeloma patients that have experienced an early relapse after intensive front line treatment, have been treated with an approved second line combination treatment regimen and obtained at least a very good partial remission (VGPR) according to International Myeloma Working Group (IMWG) criteria. Once the written informed consent is obtained, and screening procedures have been completed, harvesting of HSPCs will occur. Patients will be offered maintenance treatment during Temferon production and release. Upon Temferon release for clinical use, patients will be admitted to the transplantation unit for receipt of a reduced-intensity conditioning regimen consisting of melphalan. This will be followed by autologous stem cell transplant (ASCT) and administration of Temferon. In-patient monitoring will occur until hematological recovery occurs. Thereafter, regular follow-up of patients will occur up to 2 years (+730 days). At the +730 day visit, patients will be invited to participate in a long term follow-up study which will last for an additional 6 years.

3 cohorts of 3 patients will receive escalating doses of Temferon.

In the event that MM disease progression occurs, patients will be managed according to best clinical practice.

Being tested
Temferon
Keywords
Temferon, Gene Therapy, Immunotherapy, Hematological malignancy
Medical subject headings
Multiple Myeloma, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TemferonDrug

    Genetically modified autologous HSPCs

Study groups in NCT03875495
Study groupRoleWhat they receive
TemferonExperimentalAutologous 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.
Receives: Drug: Temferon

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 90 days

Secondary outcomes (14)

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

    0 participants analyzed. All the patients were withdrawn before treatment

    Measured: 2 years

  2. 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

    Measured: 30 days

  3. Determine the Maximum Tolerated Dose of Temferon

    Measured: 30 days

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

    Measured: Up to 2 years

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

    Measured: Up to 2 years

  6. Identify Persistence of Transduced Myeloid Cells in Bone Marrow and Peripheral Blood as Determined by Vector Copy Number

    Measured: At least 12 weeks

  7. Determine Clinical Response in Patients as Determined by IMWG Response Criteria

    Measured: Up to 2 years

  8. Fraction of Patients Achieving Complete Response With Minimal Residual Disease (MRD) Negativity

    Measured: Up to 2 years

  9. Determine Progression Free Survival in Patients

    Measured: Up to 2 years

  10. Determine Overall Survival in Patients

    Measured: 2 years

  11. Changes in Functional Status (Eastern Cooperative Oncology Group, ECOG)

    Measured: 2 years

  12. Changes in Functional Status (Karnofsky)

    Measured: 2 years

  13. Changes in Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30

    Measured: 2 years

  14. Changes in Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-MY20

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2019
  2. Study start6 Mar 2019
  3. Primary completion2 Apr 2021
  4. Study completion2 Apr 2021

Why it stopped: Failure to recruit patients

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03875495
Sponsor's protocol ID
TEM-MM-101
Status last verified
Jan 2022
First submitted
13 Mar 2019
Last updated
28 Jan 2022
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Temferon in people with Multiple Myeloma, run by Genenta Science at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tolerability and Safety of Temferon Over the First 90 Days Following Administration as Determined by the Incidence of CTCAEs (time frame: 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03875495.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2022.

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