COVID19, Hematologic Malignancy
Conditions
Keywords
SARS-CoV-2, Hematologic malignancy
Brief summary
The primary objective of this phase 2, multicentric, placebo-controlled double-blind, randomized study is to evaluate the efficacy of the combination of hydroxychloroquine and azithromycine on the viral load drop at day 5 among patients with COVID-19 and hematological malignancies.
Detailed description
The study will evaluate the effect of the combination of hydroxychloroquine and azithromycine versus placebo among 114 patients with COVID-19 and hematologic malignancy. After randomization in 1:1 ratio, patients will receive either the study treatment or placebo : * Patients enrolled in the experimental arm will receive hydroxychloroquine (200mgx3 tablets per day during 10 days) and azithromycine (500 mg at day 1 then 250mg per day during 4 days) * Patients enrolled in the control arm will receive a placebo of hydroxychloroquine (3 tablets per day during 10 days) and a placebo of azithromycine (2 capsules at day 1, then 1 capsule per day during 4 days)
Interventions
Hydroxychloroquine is an anti-malarial drug also used as anti-inflammatory treatment for systemic lupus erythematosus and rheumatic disorders. HCQ also inhibits pH-dependant replication stages of diverse types of viruses including flavivirus, retrovirus and coronaviruses.
Azithromycin is amacrolide antibiotic.
DRUGPlacebo oral tablet
Placebo of Hydroxychloroquine Sulfate 200 MG \[Plaquenil\].
DRUGPlacebo oral capsule
Placebo of Azithromycin capsules.
Sponsors
Institut de cancérologie Strasbourg Europe
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years or older patients * Patient with hematologic malignancy who received or not hematopoietic stem cell transplantation * Non severe Covid-19 disease * PCR-confirmed COVID-19 disease by a nasopharyngeal swab * Life-expectancy related to the hematologic malignancy of at least 1 month * Men or women of child-bearing potential accepting to use effective contraception during and until 8 months after the end of the study treatment
Exclusion criteria
* Patients with severe form of COVID-19 infection defined as the presence of crackles observed during clinical exam, associated with less than 94% oxygen saturation or patients with respiratory insufficiency on oxygen therapy or mechanical ventilation * Previous treatment with hydroxychloroquine or azithromycine for Covid-19 infection * QTc interval greater than 480 ms * Hypersensibility to hydroxychloroquine or azithromycine * Retinopathy * TGO or TGP geater than 5 x the normal upper limit * Creatinine clearance lower than 30 ml/min * Concomitant treatment that may lead to prolongation of the QT space * Concomitant treatment with dihydroergotamine, ergotamine, cisapride or colchicine * Known G6PD deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the efficacy of hydroxychloroquine and azithromyncine on the viral load drop at day 5. | 5 days of treatment | Locally evaluated rate of viral response. Favorable response is defined as (1) complete response : negative PCR (absence of detectable signal with a minimum of 40 cycles) or (2) major response : detectable signal but with an increased number of cycles \> or egal to 10 compared to initial PCR. Response failure is defined as (1) minor response : detectable signal but with an increased number of cycles \< 10 compared to initial PCR or (2) stabilisation or worsening of the viral load. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients progressing to a severe form | up to 3 months | Less or equal to 94% oxygen saturation - need to initiate oxygenotherapy - occurrence of respiratory distress - patient transfer in intensive care unit - need of mechanical ventilation - occurrence of non-respiratory organ failure - occurrence of septic shock |
| Mortality | up to 1 and 3 months | Date and cause of death |
| Evaluation of viral load drop | at day 10 | SARS-CoV-2 viral load by PCR on nasopharyngeal swab at day 10 (if positive at day 5) : rate of negativation and comparison of number of cycles with previous samples |
| Tolerance of study treatment | up to 3 months | Frequence and causality of all-grade cardiac adverse events - frequence and causality of grade \> 1 adverse events for other adverse events - frequence and causality of serious adverse events (CTCAE v5) |
| Evaluation of the seroconversion | at inclusion, day 10, day 30 and day 90 after treatment | Collection of serum to realize serological tests |
| Clinical evolution | up to 3 months | Duration of fever - duration of respiratory symptoms (cough, dyspnea) - duration of other COVID-19 related symptoms (digestive symptoms, ageusia, anosmia) |
| Hospitalisation duration | up to 3 months | Duration of hospitalisation (conventional, intensive care, reanimation) |
| Impact of the study treatment on the treatment of the hematological disease | up to 3 months | Patient follow-up during 3 months : hematological status and associated therapy |
| Monitoring of the QT space | at inclusion, day 2, day 5, day 10 | ECG (using connected machine to allow monitoring at home) |
| Dosage of residual concentration of azithromycine and hydroxychloroquine. | at day 5 and day 10 | Dosage of residual concentration of azithromycine and hydroxychloroquine. |
| T immunological study | at day 10 and day 30 after treatment | Phenotypic and functional study of T lymphocytes at inclusion, Retrospective analysis on frozen cells. |
| NK immunological study | at day 10 and day 30 after treatment | Phenotypic and functional study of NK lymphocytes at inclusion, Retrospective analysis on frozen cells. |
Countries
France
Outcome results
None listed