Hematologic Malignancies, Hematopoietic Stem Cell Transplant (HSCT)
Conditions
Brief summary
The purpose of this research study is to try to see whether an experimental drug, PUL 042 Inhalation Solution (PUL 042), is effective in reducing the severity of lung infections in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation with documented viral infections due to PIV, hMPV, or RSV. PUL-042 or a placebo will be administered 3 times over a 6-day period. The total duration of the study will be approximately 30 days.
Detailed description
A total of up to 100 participants will be enrolled in this research study, at up to 15 centers. Participants in the study will receive either PUL-042 or a placebo (an inactive agent that appears identical to PUL-042). Patients will be randomized 1:1 for PUL-042 or placebo. The first 50 patients will either be low dose PUL-042 or placebo. After review of the safety data from the initial patients, the PUL-042 dose may be increased. Subjects will be evaluated by chest x-ray and clinical status for respiratory complications.
Interventions
DRUGPUL-042
Pam2 : ODN (PUL-042) PUL-042 Inhalation Solution
DRUGPlacebo
Sterile Saline for Inhalation
Sponsors
Pulmotect, Inc.
Cancer Prevention Research Institute of Texas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects will be eligible for entry into the study if a nasopharyngeal swab is positive for PIV, RSV, or hMPV (as a single pathogen or a mixed infection with rhinovirus) by molecular assay by a local laboratory AND subjects must fulfill the following inclusion criteria to be eligible for participation in the study: 1. Subjects with hematologic malignancies (i.e., leukemia, lymphoma, or multiple myeloma) or recipients of an allogeneic or autologous hematopoietic stem cell transplantation for one of the following diagnoses: leukemia, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, and myelodysplastic and myeloproliferative disorder. 2. Subjects who have undergone active cytotoxic chemotherapy within 6 months or subjects who are on an immunosuppressive therapy (e.g., alemtuzumab, ibrutinib, mycophenolate mofetil, corticosteroids ≥1mg/kg prednisone equivalent). 3. Subjects who are recipients of an allogeneic hematopoietic stem cell transplant (HSCT) must be deemed high risk with an Immunodeficiency Scoring Index (ISI) , of greater or equal to 4. 4. Subjects who are recipients of an autologous HSCT must be within 3 months of the transplant procedure. 5. Subjects must be symptomatic with upper or lower respiratory tract symptoms such as rhinorrhea, sore throat or cough and must be dosed within 6 days from the onset of symptoms. 6. Chest X-ray with a Radiologic Severity Index (RSI) score of 6 or lower. 7. Subjects must have pulse oximetry of hemoglobin saturation ≥ 93% on room air. 8. Spirometry (forced expiratory volume in one second \[FEV1\] and forced vital capacity \[FVC\]) ≥70% of predicted value. 9. Adult (≥ 18 years of age). 10. If female, must be either post-menopausal (one year or greater without menses), surgically sterile, or, for female subjects of child-bearing potential who are capable of conception must be: practicing two effective methods of birth control (acceptable methods include intrauterine device, spermicide, barrier, male partner surgical sterilization, and hormonal contraception) during the study and through 30 days after completion of the study. Abstinence is not classified as an effective method of birth control. 11. If female, must not be pregnant, plan to become pregnant, or nurse a child during the study and through 30 days after completion of the study. A pregnancy test must be negative at the Screening Visit, prior to dosing on Day 1. 12. If male, must be surgically sterile or willing to practice two effective methods of birth control (acceptable methods include barrier, spermicide, or female partner surgical sterilization) during the study and through 30 days after completion of the study. Abstinence is not classified as an effective method of birth control. 13. Ability to understand and give informed consent.
Exclusion criteria
* Subjects will be excluded if they fulfill any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of PUL-042 Inhalation Solution on Lower Respiratory Tract Complications (LRTC) | 28 days | Determine efficacy of PUL-042 Inhalation Solution on lower respiratory tract complications (LRTC) using the peak post-treatment radiologic severity index (RSI) score in subjects with hematologic malignancies (HM \[lymphoma, multiple myeloma and leukemia\]) and hematopoietic stem cell transplant (HSCT) recipients with documented parainfluenza virus (PIV), human metapneumovirus (hMPV), or respiratory syncytial virus (RSV) infection. The RSI is a quantitative score based on the presence of pulmonary infiltrates in three zones in both lungs, a total of six zones. Normal in all zones would be a score of zero with a maximum score of 72, which represents total consolidation in all six zones. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Pre-Treatment through 28 days | 28 days | To determine the difference in the change from pre-treatment to peak post-treatment RSI score through 28 days. The RSI is a quantitative score based on the presence of pulmonary infiltrates in three zones in both lungs, a total of six zones. Normal in all zones would be a score of zero with a maximum score of 72, which represents total consolidation in all six zones. |
| Proportion of Subjects Positive for Each Virus at Each Sampling Timepoint | 28 days | To determine the effect of PUL-042 through 28 days for the proportion of subjects positive for each virus at each sampling timepoint. |
| Change in Viral RNA Shedding Relative to Baseline (copies/mL) | 28 days | To determine the effect of PUL-042 through 28 days for the change in viral RNA shedding relative to baseline (copies/mL). |
| Post-Treatment Viral RNA Titers (copies/mL) | 28 days | To determine the effect of PUL-042 through 28 days for post-treatment viral RNA titers (copies/mL). |
| Mortality (Incidence) | 28 days | To determine the effect of PUL-042 through 28 days for mortality (incidence). |
| Oxygenation Requirements (Days) | 28 days | The effect of PUL-042 through 28 days on the number of days on supplemental oxygen for each subject. |
| Duration of ICU Care (Days) | 28 days | To determine the effect of PUL-042 through 28 days for the duration of ICU care (days). |
| Incidence of ICU Admission | 28 days | To determine the effect of PUL-042 through 28 days for the incidence of ICU admission. |
| Duration of hospitalization (Days) | 28 days | To determine the effect of PUL-042 through 28 days for the duration of hospitalization (days). |
| Incidence of Hospitalization | 28 days | To determine the effect of PUL-042 through 28 days for the incidence of hospitalization. |
| Respiratory Symptom Scores | 28 days | To determine the effect of PUL-042 through 28 days for respiratory symptom scores (Patient reported symptoms of cough, shortness of breath, respiratory symptoms \[cough + shortness of breath\], sputum production and chest pain will each be recorded on a scale of 0 to 3 \[0=absent,1= mild, 2= moderate 3= severe\]). |
| Incidence of Pneumonia (Clinical Diagnosis) | 28 days | To determine the effect of PUL-042 through 28 days (clinical diagnosis). |
| Adverse Events | 28 days | To evaluate the incidence and severity of treatment emergent adverse events. |
| Dose/Response | 28 days | The efficacy of the 50mcg and 70mcg dose levels relative to placebo on peak RSI and change from baseline in RSI will be calculated and statistical analysis of any difference performed. The RSI is a quantitative score based on the presence of pulmonary infiltrates in three zones in both lungs, a total of six zones. Normal in all zones would be a score of zero with a maximum score of 72, which represents total consolidation in all six zones. |
Countries
United States
Contacts
CONTACTColin Broom, MD
CONTACTBrenton Scott, Ph D
PRINCIPAL_INVESTIGATORColin Broom, MD
Pulmotect, Inc.
Outcome results
None listed