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Hematopoietic and Lymphoid Cell NeoplasmPhase 1/2NCT04379518

Rintatolimod and IFN Alpha-2b for the Treatment of COVID-19 in Cancer Patients

A Phase 1/2 study testing Recombinant Interferon Alfa-2b and Rintatolimod in people with Hematopoietic and Lymphoid Cell Neoplasm and Malignant Solid Neoplasm, run by Roswell Park Cancer Institute at 1 site in United States.

Terminated

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

Official record

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Trial summary

This phase I/IIa trial studies the best dose and side effects of rintatolimod and interferon (IFN) alpha-2b in treating cancer patients with COVID-19 infection. Interferon alpha is a protein important for defense against viruses. It activates immune responses that help to clear viral infection. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Recombinant Interferon Alfa-2b and Rintatolimod
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
17 Nov 2020to 15 Mar 2023
Phase
Phase 1/2

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with cancer, with the exception of patients with active acute leukemia and allogeneic hematopoietic stem cell transplant recipients. Patients may be on active therapy or received therapy (e.g., chemotherapy, radiation or surgery) within 7 years. Patients with active cancer who have not yet been treated (e.g. newly diagnosed cancer or early stage myelodysplastic syndrome [MDS] or chronic lymphocytic leukemia [CLL]) are eligible. Basal cell cancer and carcinoma in situ treated with local excision alone do not qualify for inclusion
  • Presence of symptomatic infection, defined by fever (temperature [T] >= 38 degrees Celsius [C]) OR respiratory symptoms (cough, nasal congestion, or shortness of breath) OR lung infilitrates on chest X-ray or CT imaging. Diagnosis of COVID-19 is based on polymerase chain reaction (PCR) testing of respiratory samples.
  • Age equal to >= 18 years or older (children are excluded because COVID-19 typically has a milder course in children, and lack of safety data of this regimen in children)
  • Platelet >= 75,000/uL
  • Hemoglobin >= 9 g/dL
  • Hematocrit >= 27%
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  • Absolute neutrophil count (ANC) >= 1000/uL
  • Creatinine clearance >= 50 mL/min (Cockcroft-Gault Equation-note: plasma creatine instead of serum is used at Roswell Park)
  • Total bilirubin =< 2 X institutional upper limit of normal (ULN)
  • Aspartate transaminase (AST) (plasma) and alanine transferase (ALT) (plasma) =< 2 X institutional ULN
  • Plasma amylase and lipase =< 2 X institutional ULN
  • In the absence of COVID-19, a life expectancy of 6 months is expected
  • Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
  • NOTE: For blood chemistry labs, Roswell Park clinical blood chemistries are performed on plasma unless otherwise indicated
  • EXPANSION COHORT: Patients with cancer or allogeneic stem cell transplant recipients with and without a cancer diagnosis
  • Patients with cancer may be on active therapy or received therapy (e.g., chemotherapy, radiation or surgery) within 7 years
  • Patients with active cancer who have not yet been treated (e.g. newly diagnosed cancer or early stage MDS or CLL) are eligible
  • Basal cell cancer and carcinoma in situ treated with local excision alone do not qualify for inclusion
  • Presence of symptomatic infection, defined by fever (T >= 38.0 degrees C ) OR respiratory symptoms (cough, nasal congestion, or shortness of breath) OR lung infiltrates by chest X-ray or CT imaging. Diagnosis of COVID-19 is based on PCR testing of respiratory samples. Severe infection is excluded
  • Age equal to >= 18 years or older (children are excluded because COVID-19 typically has a milder course in children, and lack of safety data of this regimen in children). In the absence of COVID-19, a life expectancy of 6 months is expected
  • Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure. There may be specific instances when the patient can't provide informed consent, e.g. they require mechanical ventilation and are sedated, in which case a health care proxy will be able to provide informed consent. Patients with temporary cognitive impairment will be consented once their capacity has returned. Patients with chronic cognitive impairment, e.g. dementia, that precludes informed consent will not be enrolled.

Who cannot join

  • Patients with severe COVID-19 infection defined by pulmonary infiltrates on chest x-ray or computed tomography (CT) imaging plus one of the following: room air oxygen saturation (SaO2) =< 92%, room air partial pressure of oxygen (PaO2) < 70 mm Hg, or partial pressure of oxygen in arterial blood (PaO2)-PaO2 (alveolar gas) >= 35 mm Hg
  • Contraindication to recombinant (r)-INFalpha based on prior hypersensitivity, autoimmune hepatitis, decompensated liver disease
  • Patients who have active acute myeloid leukemia or acute lymphoid leukemia or are allogeneic hematopoietic stem transplant recipients. Acute leukemia in remission and chronic leukemias are not exclusion criteria
  • Cardiac events:
  • Acute coronary syndrome, myocardial infarction, or ischemia within past 3 months
  • New York Heart Association classification of III or IV congestive heart failure
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  • Unwilling or unable to follow protocol requirements
  • Patients with known serious mood disorders
  • Any additional condition, such as pre-existing inflammatory lung disease, which in the investigator's opinion deems the participant an unsuitable candidate to receive the study drugs
  • Concurrent infections, e.g. bacterial pneumonia or sepsis, that would make it difficult to evaluate clinical response to therapy or study drug toxicities
  • Therapies known to cause cytokine release syndrome (CRS), e.g. engineered T cells, within 30 days
  • Patients at high risk for tumor lysis syndrome
  • Concurrent active pneumonitis predating COVID-19, such as from checkpoint inhibitor therapy, chemotherapy-associated toxicity, or radiation pneumonitis
  • Autoimmune disease that requires systemic immunosuppression
  • Protocol-defined baseline abnormalities in cell counts, renal, or hepatic function
  • Any additional condition which in the investigator's opinion deems the participant an unsuitable candidate to receive the study drugs
  • Patients with respiratory failure requiring mechanical ventilation with FIO2 of > 60%.
  • Allogeneic hematopoietic stem cell transplant recipients with active pulmonary graft versus host disease (GvHD) (any grade)
  • Cardiac events:
  • Acute coronary syndrome, myocardial infarction, or ischemia within past 3 months,
  • New York Heart Association classification of III or IV congestive heart failure
  • Unwilling or unable to follow protocol requirements
  • Any additional condition which in the investigator's opinion deems the participant an unsuitable candidate to receive the study drugs
  • Cognitively impaired adults/adults with impaired decision-making capacity
  • Individuals who are not yet adults (infants, children, teenagers)
  • Pregnant women
  • Prisoners

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: Phase 1/2A Study of Rintatolimod and IFN Alpha Regimen in Cancer Patients With COVID-19

This phase I/IIa trial studies the best dose and side effects of rintatolimod and interferon (IFN) alpha-2b in treating cancer patients with COVID-19 infection. Interferon alpha is a protein important for defense against viruses. It activates immune responses that help to clear viral infection. Rintatolimod is double stranded ribonucleic acid (RNA) designed to mimic viral infection by stimulating immune pathways that are normally activated during viral infection. Giving rintatolimod and interferon alpha-2b may activate the immune system to limit the replication and spread of the virus.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety of the combination of intravenous (i.v.) rintatolimod administered with or without i.v. IFN alpha (recombinant interferon alfa-2b [Intron A]) in patients with cancer with coronavirus disease 2019 (COVID-19).

II. Determine the kinetics of viral load in nasopharyngeal swabs in the course of treatment and Days 7 and 14.

SECONDARY OBJECTIVES:

  1. To assess the efficacy of the treatment combination in patients with cancer with COVID-19.

II. Determine the kinetics of viral load in the peripheral blood in the course of treatment and Days 7 and 14.

III. Determine the kinetics of changes of the immune subsets and circulating inflammatory mediators (including C-reactive protein [CRP], cytokines, chemokines, interferons) in peripheral blood in the course of treatment and Days 7 and 14.

IV. Determine the induction of known mediators of antiviral immunity that include (myxovirus resistance gene, MxA; protein Kinase R (PKR); oligoadenylate synthetase-2 (OAS2); RNAse-L, IFN-stimulated gene-15 (ISG15); IFN-induced proteins with tetratricopeptide repeats (IFIT1) and IFN-inducible transmembrane protein 3 (IFITM3), TLR3, RIG-I, MDA5, IRF3, IRF7, in nasopharyngeal swabs material and blood cells of patients on all tiers of treatment.

OUTLINE: This is a phase I, dose-escalation study of recombinant interferon alfa-2b followed by a phase II study.

LEAD-IN PHASE: Patients receive rintatolimod IV over 2.5-3 hours on day 1 and day 3 (or 4).

ARM I: Patients receive rintatolimod IV over 2.5-3 hours and recombinant interferon alfa-2b IV over 20 minutes on day 1 and on day 3 or 4 in the absence of disease progression or unacceptable toxicity.

EXPANSION COHORT:

ARM III: Patients receive rintatolimod IV over 2.5-3 hours along with standard of care.

Patients are followed up at days 7, 14 and 30 after initiation of the study regimen.

Being tested
Recombinant Interferon Alfa-2b, Rintatolimod
Medical subject headings
Hematologic Neoplasms

What participants receive

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

  • Recombinant Interferon Alfa-2bBiological

    Also called Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B

    Given IV

  • RintatolimodDrug

    Also called Ampligen, Atvogen

    Given IV

Study groups in NCT04379518
Study groupRoleWhat they receive
Rintatolimod, recombinant interferon alfa-2b 0 MU/M^2ExperimentalDose level 1:Patients receive rintatolimod IV over 2.5-3 hours plus recombinant interferon alfa-2b IV 0 over 20 minutes on day 1 and on day 3 (or 4) in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod
Rintatolimod, recombinant interferon alfa-2b 5 MU/M^2ExperimentalDose level 2 :Patients receive rintatolimod IV over 2.5-3 hours plus recombinant interferon alfa-2b IV 5 MU/M^2 over 20 minutes on day 1 and on day 3 (or 4) in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod
Rrintatolimod plus Standard of Care)ExperimentalPatients receive rintatolimod IV over 2.5-3 hours once plus standard of care.
Receives: Drug: Rintatolimod
Rintatolimod, recombinant interferon alfa-2b 10 MU/M^2ExperimentalDose level 3: Patients receive rintatolimod IV over 2.5-3 hours plus recombinant interferon alfa-2b IV 10 MU/M^2 over 20 minutes on day 1 and on day 3 (or 4) in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod
Rintatolimod, recombinant interferon alfa-2b 20 MU/M^2ExperimentalDose level 4: Patients receive rintatolimod IV over 2.5-3 hours plus recombinant interferon alfa-2b IV 20 MU/M^2 over 20 minutes on day 1 and on day 3 (or 4) in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod

What is being measured

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

  1. Number of Participants With Adverse Events (AEs)

    This refers to the frequency of grade 3 or 4 AEs considered to be probably or definitely related to the treatment regimen. Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE version [v] 5.0).

    Measured: Up to 30 days post treatment initiation, On average, the timeframe is 25 days

  2. Kinetics of Viral Load

    Will be assessed as cycle threshold values in nasopharyngeal swabs based on quantitative polymerase chain reaction (PCR) in the course of treatment and days 1, 3/4, 7, and 11.

    Measured: Treatment and days 1, 3/4, 7 and 11

Secondary outcomes (22)

  1. Number of Participants With Selected Clinical Efficacy Complications

    Will be assessed by the frequency of these complications: (i) progression of infection requiring hospitalization; (ii) respiratory failure requiring mechanical ventilation (primary efficacy endpoint); and (iii) death within 30 days. If present, acute respiratory distress syndrome will be graded by Berlin criteria.

    Measured: Up to 30 days post treatment initiation

  2. Kinetics of Viral Load

    Will be assessed as cycle threshold values in the peripheral blood and nasopharyngeal swab based on quantitative PCR in the course of treatment and days 1, 3, 7, and 14.

    Data entered are values that were measured, no "placeholders" were entered, zero is a valid measurement.

    Measured: Days 1, 3, 7, 14 post treatment initiation

  3. Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (COX2)

    Gene expresssion measured by qPCR

    Measured: Days 1, 4 , 7, 14 and 30 post treatment initiation

  4. Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL5)

    Gene expression measured by QPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  5. Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL10)

    Gene expression measured by qPCR

    Measured: Days 1, 4, 7, 14, and 30 post treatment

  6. Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL22)

    Gene expression measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  7. Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL12)

    Gene expression measured by qPCR

    Measured: Days 1, 4, 7, and 30 post treatment

  8. Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IL-10)

    gene expression measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  9. Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IDO1)

    Gene expression measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  10. Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNB1)

    Gene expression measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  11. Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNa)

    Gene expression measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  12. Known Mediators of Antiviral Immunity (RIG-1)

    Induction of known mediator RIG-1 of antiviral immunity measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  13. Known Mediators of Antiviral Immunity (TLR-3)

    Induction of known mediator TLR-3 of antiviral immunity measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  14. Known Mediators of Antiviral Immunity (ISG-15)

    Induction of known mediator ISG-15 of antiviral immunity measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  15. Known Mediators of Antiviral Immunity (RNAseL)

    Induction of known mediator RNAseL of antiviral immunity measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  16. Known Mediators of Antiviral Immunity (OAS2)

    Induction of known mediator OAS2 of antiviral immunity measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  17. Known Mediators of Antiviral Immunity (ACE2)

    Induction of known mediator ACE2 of antiviral immunity measured by qPCR

    Measured: Days 1, and 14 post treatment

  18. Known Mediators of Antiviral Immunity (Mx1)

    Induction of known mediator Mx1 of antiviral immunity measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  19. Known Mediators of Antiviral Immunity (IFIT1)

    Induction of known mediator IFIT1 of antiviral immunity measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  20. Known Mediators of Antiviral Immunity (IFITM3)

    Induction of known mediator IFITM3 of antiviral immunity measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  21. Known Mediators of Antiviral Immunity (IRF3)

    Induction of known mediator IRF3 of antiviral immunity measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

  22. Known Mediators of Antiviral Immunity (IRF7)

    Induction of known mediator IRF7 of antiviral immunity measured by qPCR

    Measured: Days 1, 4, 7, 14 and 30 post treatment

Timeline

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

  1. First posted7 May 2020
  2. Study start17 Nov 2020
  3. Primary completion15 Mar 2023
  4. Study completion15 Mar 2023

Why it stopped: Low accrual

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04379518
Sponsor's protocol ID
I 659920
Other IDs
NCI-2020-02317, I 659920, P30CA016056
Status last verified
Jan 2026
First submitted
6 May 2020
Last updated
13 Jan 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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