Lymphoma, Myeloma Multiple
Conditions
Keywords
vitamin C, ascorbate, ascorbic acid, autologous stem cell transplantation
Brief summary
In the study the investigators will randomize patients that receive an autologous stem cell transplantation for myeloma or lymphoma for treatment with vitamin C or placebo during 6 weeks. Primary endpoint will be immune recovery.
Detailed description
Rationale: Recent studies showed that ascorbic acid (AA) stimulates proliferation and maturation of T lymphocytes and natural killer (NK) cells. Chemotherapy results in depletion of those cells and thereby an increased infection rate. A pilot study showed low levels of AA in the plasma of several patients after chemotherapy followed by autologous stem cell transplantation for hematological malignancies. AA supplementation could be beneficial to the recovery of the immune system in these patients. Objective: The aim of this study is to examine the effect of vitamin C supplementation on immune recovery in patients with autologous stem cell transplantation. The aim of the run-in phase of the study is to examine the effect of intravenous vitamin C supplementation on plasma concentrations of vitamin C in patients with autologous stem cell transplantation at day 14 in order to be sure that in the intervention study accurate AA plasma levels will be present. Study design: run-in phase, followed by randomized controlled trial Study population: All participants will be adults (minimally 18 years old) that are planed to receive an autologous stem cell transplantation for multiple myeloma or lymphoma and are recruited at the MUMC+. In total there will be 3 expected (run-in phase) + 44 (randomized controlled trial) participants. Main study parameters/endpoints: Primary endpoints will be AA plasma level on day 14 (run-in phase) and the day of neutrophil recovery after stem cell transplantation (randomized-controlled phase). Secondary endpoints will be AA leukocyte levels, infection rate, duration of hospital stay, side effects of chemotherapy, overall survival, coagulation parameters, platelet reactivity, fibrinolysis and quality of life. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: AA supplementation could be beneficial for the immune recovery in the participants of this study. The risks associated with participation in this study are low. Vitamin C supplementation is safe and hardly has any documented side effects.
Interventions
DRUGVitamin C
vitamin C intravenous during hospitalization, after oral, total 6 weeks.
DRUGPlacebos
placebo intravenous during hospitalization, after oral, total 6 weeks
Sponsors
Maastricht University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
double blind placebo-controlled randomized trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years or older * written informed consent * diagnosis of malignant lymphoma or multiple myeloma * require chemotherapy plus autologous stem cell transplantation as standard of care for the disease at that stage * central venous catheter in place or planned
Exclusion criteria
* inability to understand the nature and extent of the trial and the procedures required * history of kidney stones * kidney failure requiring dialysis or eGFR \<30 mL/min. (CDK-EPI formula) * history of G6PD deficiency * life expectancy \< 1 month * use of immunosuppressive medication other than chemotherapy and corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| immune recovery | day 14-28 | the day of repopulation (return of neutrophil to at least 0.5 × 109/l) after autologous stem cell transplantation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AA leukocyte levels | day 14 | AA leukocyte levels |
| Incidence of infections/ neutropenic fever | day 1-28 | fever and infections during hospitalization |
| Days of hospitalization | dag 1-28 | number of days patients are admitted in our hospital |
| Days with fever (≥ 38.5° C) | day 1-28 | Amount of days admitted patients have a fever |
| Incidence of bloodstream infections | day1-28 | number of bloodstream infections of admitted patients |
| Quality of life according to the EORTC QLQ-C30 | Day 0, day 14, day 42 | quality of live questionaire |
| AA plasma levels | day 14 | AA plasma levels |
| Relapse rates (3 months) | 3 months | relapse rate at 3 months |
| Use of systemic antimicrobial agents (incidence and duration) | dau 1-28 | use of antibiotics during hospitalization |
| platelet reactivity | day 10 | platelet reactivity tests |
| ROS production | day 10 | ROS production platelets |
| platelet mitochondrial dysfunction | day 10 | platelet mitochondrial function test |
| number and severity of bleeding episodes during admission | day 1-28 | number and severity of bleeding episodes during admission |
| Overall survival (3 months) | 3 months | overall survival at 3 months |
Countries
Netherlands
Outcome results
None listed