Study of Nicotinamide Riboside Supplementation in Allogeneic Hematopoietic Cell Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to find a safe and tolerable way to improve engraftment after transplant. Research studies have shown that adding nicotinamide riboside to donor cells has the potential to increase blood stem cell numbers and potentially decrease the time to engraftment. Also, nicotinamide riboside, TRU NIAGEN (the study drug) is a type of vitamin B supplement that the general public can get without a prescription and is well tolerated.

Detailed Description
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This is a single-center, pilot feasibility study of NR supplementation in allogeneic (donor) HCT in which the study team is seeking to obtain preliminary data on any beneficial effect of increasing NAD+ levels in-vivo to facilitate engraftment. Engraftment is defined as the process during which transplanted stem cells begin to grow in the bone marrow and produce new white blood cells, red blood cells, and platelets. It takes about 14 to 24 days for donor cells to engraft after infusion, and the time between which blood counts fall to the time when they recover is a very critical period. Transfusions are frequently required to prevent bleeding and antibiotics are needed to prevent infections during this critical time period. Shortening the time of engraftment decreases these risks and can improve long-term health status. The primary objectives of this study is to evaluate safety and tolerability of NR supplementation The secondary objective of this study is to evaluate neutrophil and platelet recovery after HCT

Official Title
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A Pilot Study of Nicotinamide Riboside Supplementation in Allogeneic Hematopoietic Cell Transplantation

Conditions
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Allogeneic Hematopoietic Cell Transplantation

Intervention / Treatment
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* Drug: Nicotinamide riboside (NR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All disease indications for allogeneic hematopoietic cell transplantation except for myelofibrosis. Subject must meet program eligibility criteria* for myeloablative conditioning alloHCT and plan to undergo myeloablative conditioning. HLA-identical related donor or unrelated human donor source with bone marrow graft. Subjects must provide a written informed consent. Exclusion Criteria: History of allergy or intolerance to NR precursor compounds, including niacin or nicotinamide Pregnant or breastfeeding women are excluded from this study since allogeneic HCT is a strict contraindication. Subjects with uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotinamide riboside (NR)<br> | Drug: Nicotinamide riboside (NR)<br>* Nicotinamide riboside, PO, 500mgtwice daily for 21, 28, and 35 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of participants who receive >75% of scheduled doses. | Tolerability of NR in allogeneic HCT recipients, defined as 8 or more of 15 participants (i.e. at least 50% of enrolled subjects) able to receive >75% of their scheduled doses (overall rate 53%, 95% confidence intervals 33%-86%). This will include both patients who discontinue NR due to study drug related toxicity and patients who are not able to stay on NR due to transplant related toxicity that limits ability to take the drug | day +7 | 
| Percent of participants who receive >75% of scheduled doses. | Tolerability of NR in allogeneic HCT recipients, defined as 8 or more of 15 participants (i.e. at least 50% of enrolled subjects) able to receive >75% of their scheduled doses (overall rate 53%, 95% confidence intervals 33%-86%). This will include both patients who discontinue NR due to study drug related toxicity and patients who are not able to stay on NR due to transplant related toxicity that limits ability to take the drug | day +14 | 
| Percent of participants who receive >75% of scheduled doses. | Tolerability of NR in allogeneic HCT recipients, defined as 8 or more of 15 participants (i.e. at least 50% of enrolled subjects) able to receive >75% of their scheduled doses (overall rate 53%, 95% confidence intervals 33%-86%). This will include both patients who discontinue NR due to study drug related toxicity and patients who are not able to stay on NR due to transplant related toxicity that limits ability to take the drug | day +21 | 
| Percent of participants experiencing a CTCAE 5.0 grade 3 or higher related to the study drug | Safety of NR in allogeneic HCT recipients as measured by percent of participants experiencing a CTCAE 5.0 grade 3 or higher that is related to the study drug | day +7 | 
| Percent of participants experiencing a CTCAE 5.0 grade 3 or higher related to the study drug | Safety of NR in allogeneic HCT recipients as measured by percent of participants experiencing a CTCAE 5.0 grade 3 or higher that is related to the study drug | day +14 | 
| Percent of participants experiencing a CTCAE 5.0 grade 3 or higher related to the study drug | Safety of NR in allogeneic HCT recipients as measured by percent of participants experiencing a CTCAE 5.0 grade 3 or higher that is related to the study drug | day +21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median days to neutrophil recovery after HCT | Median and range of days to neutrophil recovery after HCT. Recovery defined as first day of three consecutive days with absolute neutrophil count 500 cells/mm3 (0.5 x 109/L) or greater | Up to 100 days from start of treatment | 
| Median days to platelet recovery after HCT | Median and range of days to Platelet recovery after HCT. Recovery defined as first day of three consecutive days with platelet count 20,000/mm3 (20 x 109/L) or greater and unsupported by platelet transfusions. | Up to 100 days from start of treatment |