Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03176849
Other study ID # 17-076
Secondary ID
Status Completed
Phase Phase 4
First received
Last updated
Start date November 1, 2017
Est. completion date July 1, 2019

Study information

Verified date November 2020
Source Phoenix Children's Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Research has suggested that children with sufficient vitamin D levels undergoing hematopoietic stem cell transplant (HSCT) have improved outcomes, including lower incidences of infection and graft-versus-host disease (GVHD), as well as overall improved survival. However, supplementation in children undergoing HSCT has shown to be a challenge using standard or aggressive supplementation strategies. The primary objective of this study is to determine the safety and efficacy of a single, high dose oral vitamin D (Stoss Therapy) at the start of transplant followed by maintenance supplementation in children undergoing HSCT.


Description:

Comorbidities and complications including infection, organ system toxicity, graft-versus-host disease (GVHD) and disease recurrence are some of the biggest contributors to quality of life and mortality in children undergoing hematopoietic stem cell transplant (HSCT). Research has suggested that patients with sufficient vitamin D levels during transplant have improved outcomes, including lower incidences of infection and acute GVHD, as well as overall improved survival. Prior research has shown that chronically ill children are at risk for vitamin D deficiency, including those undergoing HSCT. Data has shown populations with as many as 70% of HSCT patients have insufficient levels of vitamin D at time of transplant. While several studies have attempted methods of vitamin D supplementation in this subset of patients, there has not been success with either standard or aggressive supplementation strategies. Single high-dose oral vitamin D therapy, known as stoss therapy, has been used in other chronically ill children where adequate levels of vitamin D are difficult to attain. Stoss therapy suggests a single high-dose followed by maintenance dosing would be adequate to replete and maintain vitamin D levels in chronically ill children. While it has been shown to be effective with no evidence of toxicity in patients with rickets and cystic fibrosis, its safety and efficacy has not been studied in the transplant setting. However, there is an urgent need to identify a modifiable factor may reduce the occurrence and/or severity of HSCT associated complications. The overall objective of this study is to determine the effectiveness of a single, high dose oral vitamin D (Stoss Therapy) followed by maintenance supplementation in children undergoing HSCT. This change will result in a new and innovative approach to maintaining adequate vitamin D levels during pediatric HSCT, with the long term goal of reducing morbidity and mortality. Our primary goal is to assess the safety and efficacy of a single, high dose of vitamin D followed by maintenance supplementation in children undergoing HSCT. Our secondary goal is to identify the effects of adequate vitamin D levels on early clinical outcomes such as cytokine levels, graft versus host disease, immune recovery, rejection, relapse, infection rates in pediatric HSCT patients.


Recruitment information / eligibility

Status Completed
Enrollment 49
Est. completion date July 1, 2019
Est. primary completion date July 1, 2019
Accepts healthy volunteers No
Gender All
Age group 1 Year to 25 Years
Eligibility Inclusion Criteria: - All pediatric patients, ages 1 to 25 years of age, undergoing hematopoietic stem cell transplant at Phoenix Children's hospital - Patients must sign an informed consent Exclusion Criteria: - Prior rejection of hematopoietic stem cell transplant

Study Design


Intervention

Dietary Supplement:
Vitamin D3
The single, oral dose of vitamin D3 is based on patient's age and baseline 25-hydroxy-vitamin D level. Dosing is as follows: (1) For children under 3 years of age. 200000IU for those deficient, 150000IU for those insufficient, and 100000IU for those sufficient; (2) For children 3-12 years of age, 400000IU for those deficient, 350000IU for those insufficient, and 200000IU for those sufficient; (3) For children greater than 12 years of age, 600000IU for those deficient, 500000IU for those insufficient, and 300000IU for those sufficient. This is a single, one time oral dose given prior to the start of transplant.
Standard Vitamin D3 Supplementation
Those who have sufficient vitamin D will be supplemented with 400-600IU/day of Vitamin D3 orally. Those who have insufficient or are deficient in vitamin D will be supplemented with 50,000IU/week of Vitamin D3 orally.

Locations

Country Name City State
United States Phoenix Children's Hospital Phoenix Arizona

Sponsors (1)

Lead Sponsor Collaborator
Phoenix Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (12)

Duncan CN, Vrooman L, Apfelbaum EM, Whitley K, Bechard L, Lehmann LE. 25-hydroxy vitamin D deficiency following pediatric hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2011 May;17(5):749-53. doi: 10.1016/j.bbmt.2010.10.009. Epub 2010 Oct 15. — View Citation

Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004 Jun;158(6):531-7. — View Citation

Hansson ME, Norlin AC, Omazic B, Wikström AC, Bergman P, Winiarski J, Remberger M, Sundin M. Vitamin d levels affect outcome in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014 Oct;20(10):1537-43. doi: 10.1016/j.bbmt.2014.05.030. Epub 2014 Jun 5. — View Citation

Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW. 25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Am J Clin Nutr. 2008 Jun;87(6):1738-42. — View Citation

Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. doi: 10.1210/jc.2011-0385. Epub 2011 Jun 6. Erratum in: J Clin Endocrinol Metab. 2011 Dec;96(12):3908. — View Citation

Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M; Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008 Aug;122(2):398-417. doi: 10.1542/peds.2007-1894. Review. — View Citation

Rosenblatt J, Bissonnette A, Ahmad R, Wu Z, Vasir B, Stevenson K, Zarwan C, Keefe W, Glotzbecker B, Mills H, Joyce R, Levine JD, Tzachanis D, Boussiotis V, Kufe D, Avigan D. Immunomodulatory effects of vitamin D: implications for GVHD. Bone Marrow Transplant. 2010 Sep;45(9):1463-8. doi: 10.1038/bmt.2009.366. Epub 2010 Jan 18. — View Citation

Schlereth F, Badenhoop K. [Vitamin D : More than just a bone hormone]. Internist (Berl). 2016 Jul;57(7):646-55. doi: 10.1007/s00108-016-0082-2. Review. German. — View Citation

Shepherd D, Belessis Y, Katz T, Morton J, Field P, Jaffe A. Single high-dose oral vitamin D3 (stoss) therapy--a solution to vitamin D deficiency in children with cystic fibrosis? J Cyst Fibros. 2013 Mar;12(2):177-82. doi: 10.1016/j.jcf.2012.08.007. Epub 2012 Sep 19. — View Citation

Sullivan SS, Rosen CJ, Halteman WA, Chen TC, Holick MF. Adolescent girls in Maine are at risk for vitamin D insufficiency. J Am Diet Assoc. 2005 Jun;105(6):971-4. — View Citation

Wallace G, Jodele S, Howell J, Myers KC, Teusink A, Zhao X, Setchell K, Holtzapfel C, Lane A, Taggart C, Laskin BL, Davies SM. Vitamin D Deficiency and Survival in Children after Hematopoietic Stem Cell Transplant. Biol Blood Marrow Transplant. 2015 Sep;21(9):1627-31. doi: 10.1016/j.bbmt.2015.06.009. Epub 2015 Jun 18. — View Citation

Wallace G, Jodele S, Myers KC, Dandoy CE, El-Bietar J, Nelson A, Taggart CB, Daniels P, Lane A, Howell J, Teusink-Cross A, Davies SM. Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation Patients Despite Both Standard and Aggressive Supplementation. Biol Blood Marrow Transplant. 2016 Jul;22(7):1271-1274. doi: 10.1016/j.bbmt.2016.03.026. Epub 2016 Apr 1. — View Citation

* Note: There are 12 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Safety of Stoss Therapy In order to monitor the safety of stoss therapy, patients will be monitored for any clinical signs or symptoms of hypervitaminosis D, including abdominal pain, dehydration, and fatigue. Patients will be monitored for hypercalcemia and hyperphosphatemia with weekly complete metabolic panels and serum phosphorus during the first 100 days of transplant. Patients will have repeat measurements of serum 25(OH)D levels will be obtained at Day +30 to ensure they do not have hypervitaminosis D at that time. 100 days
Primary Efficacy of vitamin D repletion All patients will have baseline serum 25(OH)D levels obtained prior to transplant. At baseline, patient will be classified as being sufficient (>30ng/mL), insufficient (21- 29ng/mL), or deficient (<20ng/mL) in serum vitamin D. All patients will then undergo treatment based on their trial arm and baseline levels of vitamin D. Patients will have repeat measurements of serum 25(OH)D levels will be obtained at Day +100 of transplant. At this time they will again be classified as being sufficient (>30ng/mL), insufficient (21- 29ng/mL), or deficient (<20ng/mL) in serum vitamin D following therapy to assess if the therapy was efficacious in repleting and maintaining their serum vitamin D level. 100 days
Secondary Graft-versus-host disease All incidences of GVHD will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100 100 days
Secondary Immune Recovery Immune recovery will be obtained at Day +100 as per standard of care and recorded in the medical record 100 days
Secondary Rejection All incidences of rejection will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100 100 days
Secondary Relapse All incidences of relapse will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100 100 days
Secondary Infection Rates All incidences of infection will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100 100 days
Secondary Mortality All incidences of mortality will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100 100 days
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Terminated NCT04313881 - Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS) Phase 3
Recruiting NCT05088356 - Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft Phase 1
Recruiting NCT04003220 - Idiopathic Chronic Thrombocytopenia of Undetermined Significance : Pathogenesis and Biomarker
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Active, not recruiting NCT03755414 - Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation Phase 1
Completed NCT00003270 - Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer Phase 2
Recruiting NCT04904588 - HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide Phase 2
Terminated NCT04866056 - Jaktinib and Azacitidine In Treating Patients With MDS With MF or MDS/MPN With MF. Phase 1/Phase 2
Recruiting NCT04701229 - Haploinsufficiency of the RBM22 and SLU7 Genes in Del(5q) Myelodysplastic Syndromes
Suspended NCT04485065 - Safety and Efficacy of IBI188 With Azacitidine in Subjects With Newly Diagnosed Higher Risk MDS Phase 1
Recruiting NCT04174547 - An European Platform for Translational Research in Myelodysplastic Syndromes
Enrolling by invitation NCT04093570 - A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers Phase 2
Completed NCT02508870 - A Study of Atezolizumab Administered Alone or in Combination With Azacitidine in Participants With Myelodysplastic Syndromes Phase 1
Completed NCT04543305 - A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies Phase 1
Recruiting NCT05384691 - Efficacy of Luspatercept in ESA-naive LR-MDS Patients With or Without Ring Sideroblasts Who do Not Require Transfusions Phase 2
Recruiting NCT05365035 - A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts Phase 2
Recruiting NCT06008405 - Clinical Trial Evaluating the Safety of the TQB2928 Injection Combination Therapy Phase 1
Not yet recruiting NCT05969821 - Clonal Hematopoiesis of Immunological Significance
Withdrawn NCT05170828 - Cryopreserved MMUD BM With PTCy for Hematologic Malignancies Phase 1