Clinical trial NCT04426201: InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic Patients With COVID-19 Infection ( ILIAD-7-US-O )
Official title: A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection. US Oncology Cohort
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Lymphocytopenia
Lead sponsor: Revimmune
Sponsor class: INDUSTRY
Collaborators: name: Memorial Sloan Kettering Cancer Center
name: Amarex Clinical Research
name: M.D. Anderson Cancer Center
name: Cancer Research Institute, New York City
First posted: 2020-06-11
Enrollment: 10
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled of treatment vs placebo
Primary purpose: TREATMENT

Brief summary: Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients

Detailed description: Approximately forty-eight (48) participants will be randomized 1:1 to receive

(a) Intramuscular (IM) administration of CYT107 at 10 μg/kg followed, after 72hrs of observation, by 10 μg/kg twice a week for 3 weeks (maximum 7 administrations adjusted to patient's length of stay in the hospital) or (b) Intramuscular (IM) placebo (normal saline) at the same frequency.

The aim of the study is to test the ability of CYT107 to produce an immune reconstitution of these patients and observe possible association with a clinical improvement.

This cohort is dedicated to oncology patients

Eligibility criteria: Inclusion Criteria:

1. A written, signed informed consent, or emergency oral consent, by the patient or the patient's legally authorized representative, and the anticipated ability for participant to be re-consented in the future for ongoing Study participation
2. Patient receiving active or recent chemotherapy or immunotherapy (within 6 months) for cancer (and/or)
3. Patients who have received hematopoietic stem cell transplantation (for a diagnosis other than lymphoma) within the past 1 year (and/or)
4. Patients who received CAR-T cell therapy within the past 1 year (but not within last 30 days- see also exclusion criteria number 6 \& 7) (and/or)
5. Patients receiving hormonal therapy for cancer (and/or)
6. Patients who have undergone surgery or radiotherapy for cancer within the past 6 months
7. Patients with newly diagnosed (biopsy proven) malignancy who have not yet received cancer treatment but get COVID pneumonia in the interim (Incl. Criteria 11)
8. Men and women aged ≥ 25 - 80 (included) years of age
9. Hospitalized patients with one absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, collected at baseline or no more than 72h before baseline .

   From this time point the investigator may choose to further postpone the commencement of IL-7 (CYT107) treatment according to patient's clinical status.
10. Hospitalized patients with moderate to severe hypoxemia requiring oxygen therapy at \>4L per minute nasal cannula or greater to keep saturations \>90%, non-invasive positive pressure ventilation (e.g., BIPAP), or patients intubated/ventilated for respiratory failure
11. Confirmed infection with COVID-19 by any acceptable test available/utilized at each site
12. Willingness and ability to practice contraception regardless of the gender of the patient during 5 months after last drug exposure

Exclusion Criteria:

1. Pregnancy or breast feeding;
2. ALT and/or AST \> 5 x ULN
3. Known, active auto-immune disease;
4. Patients with a history of lymphoid malignancy
5. Patients with any malignancy that is present at time of enrollment where treating physician expects life expectancy due to the underlying malignancy to be less than 6 months
6. Patients who received CAR-T cell therapy within the past 30 days or with unresolved cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS)
7. Patients with unresolved grade \> 2 toxicities from prior chemotherapy, immunotherapy, or CAR-T cell therapy
8. Patients with past history of Solid Organ transplant.
9. Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load.
10. Hospitalized patients with refractory hypoxia, defined as inability to maintain saturation \>85% with maximal available therapy for \>6 hours
11. Patients with a mechanical ventilation support ≥ 7 days
12. Patients with chronic kidney dialysis
13. Patients with a SOFA score ≥ 9 at baseline
14. Patients with a BMI \> 40
15. Patients showing an increase of the NEWS2 score by more than 6 points during the screening/ baseline period (48 to 72 hrs prior to first administration)
16. Patients with hospital admission Rockwood Clinical Frailty Scale ≥ 6. (assessed as patient or proxy 4-week recall of chronic health and frailty status prior to COVID infection)

11. Patients under guardianship

Primary outcomes:
measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first
timeFrame: one month
Secondary outcomes:
measure: To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.
timeFrame: one month
measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD
timeFrame: 1 month or HD (whichever occurs first)
measure: frequency of secondary infections through day 45 compared to placebo arm
timeFrame: 45 days
measure: length of hospitalization compared to placebo arm
timeFrame: 45 days
measure: length of stay in ICU compared to placebo arm
timeFrame: 45 days
measure: number of readmissions to ICU compared to placebo arm
timeFrame: 45 days
measure: organ support free days compared to placebo arm
timeFrame: 45 days
measure: Frequency of re-hospitalization through day 45 compared to placebo arm
timeFrame: 45 days
measure: All-cause mortality through day 45 compared to placebo arm
timeFrame: 45 days
measure: CD4+ and CD8+ T cell counts compared to placebo arm
timeFrame: 30 days
measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm
timeFrame: 30 days
measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm
timeFrame: 30 days
measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm
timeFrame: 30 days
measure: Physiological status through NEWS2 evaluation compared to Placebo arm
timeFrame: 30 days
Other outcomes:
measure: Safety assessment through incidence and scoring of grade 3-4 adverse events
timeFrame: 45 days
Locations:
city: New York
country: United States
facility: Memorial sloan kettering
state: New York
city: Houston
country: United States
facility: MD Anderson cancer center
state: Texas
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Steve Pastores, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Marcel van den Brink, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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