Zinc as Enhancer in Immune Recovery After Stem Cell Transplantation for Hematological Malignancies (ZENITH)

A Mono-centric, No-profit, Case-control Study With Daily Oral Supplementation of Zinc Sulphate After Autologous Stem Cell Transplantation in Patients Affected by Multiple Myeloma

Patients affected by multiple myeloma undergone autologous stem cell transplantation (SCT) are enrolled at the moment of stem cell collection. They are randomized 1:1 in two groups at the moment of the graft. Patients of the Control group take only standard antimicrobial prophylaxis after SCT; the Sample group takes in addition a daily oral supplementation of Zinc Sulfate (600 mg/die) from day +5 until day +100 after SCT. Laboratory tests are performed on peripheral blood samples.

Study Overview

• Status: Completed
• Conditions: Stem Cell Transplant Complications
• Intervention / Treatment: Drug: Levofloxacin 500Mg Oral Tablet; Drug: Fluconazole 200mg tab; Drug: Acyclovir 400 MG; Drug: Zinc Sulfate Oral Product

Detailed Description

Patients affected by multiple myeloma undergone autologous stem cell transplantation (SCT) are enrolled at the moment of stem cell collection. They are randomized 1:1 in two groups at the moment of the graft. Patients of the Control group take only standard antimicrobial prophylaxis after SCT; the Sample group takes in addition a daily oral supplementation of Zinc Sulfate (600 mg/die) from day +5 until day +100 after SCT. The aim of the study is to investigate the immune reconstitution in presence of Zinc, focused on thymic reconstitution. Laboratory tests are performed on peripheral blood samples, collected at 4 time-points: two before transplant (at the moment of the enrollment and the day before conditioning) and two after transplant (day +30 and +100).

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Pisa, Italy, 56126
    • Hematology UO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• eligibility to stem cell transplantation

Exclusion Criteria:

• allergy to Zinc
• copper deficiency or Wilson's syndrome
• patients who admit zinc assumption in other drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Control; patients undergone autologous stem cell transplantation. They take levofloxacin 500 mg/d, aciclovir 400 mg bid, fluconazole 200 mg bid from day +10 until day +30 after stem cell transplantation	Drug: Levofloxacin 500Mg Oral Tablet; once daily from day +10 until day +30 after stem cell transplantation; Drug: Fluconazole 200mg tab; twice daily from day +10 until day +30 after stem cell transplantation; Drug: Acyclovir 400 MG; twice daily from day +10 until day +30 after stem cell transplantation
EXPERIMENTAL: Zinc; patients undergone autologous stem cell transplantation. They take the same antimicrobial prophylaxis of patients of the Control group, and, in addition, a daily oral supplementation of Zinc Sulfate, 600 mg/die, uncoated tabs, from day +5 until day +100 after transplant	Drug: Levofloxacin 500Mg Oral Tablet; once daily from day +10 until day +30 after stem cell transplantation; Drug: Fluconazole 200mg tab; twice daily from day +10 until day +30 after stem cell transplantation; Drug: Acyclovir 400 MG; twice daily from day +10 until day +30 after stem cell transplantation; Drug: Zinc Sulfate Oral Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thymic output improvement by TRECs	Measure of T cell receptor excision circles levels on peripheral lymphocytes (TRECs), calculated as number of copies of TRECs/mcLin droplet digital PCR	increase of TRECs levels from day +30 until day +100 after transplant
Thymic output improvement by flow cytometry	Measure of circulating T naive lymphocytes by 8-colour flow-cytometry. T naive are identified as CD4+/CD8+ lymphocytes with the coexpression of CD45RA, CD27, CD28. The value is estimated as number of T naive/mcL	days +30, +100 after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variations in circulating lymphocyte populations	Flow cytometry to determine the variations of t cell subpopulations after graft	days +30, +100 after transplant
Immune competence	quantitative polymerase chain reaction on peripheral blood aiming to quantify Torquetenovirus viral load	days +30, +100 after transplant
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	case report form to report side effects	days +30, +100 after transplant

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero, Universitaria Pisana

Publications and helpful links

General Publications

• Iovino L, Mazziotta F, Carulli G, Guerrini F, Morganti R, Mazzotti V, Maggi F, Macera L, Orciuolo E, Buda G, Benedetti E, Caracciolo F, Galimberti S, Pistello M, Petrini M. High-dose zinc oral supplementation after stem cell transplantation causes an increase of TRECs and CD4+ naive lymphocytes and prevents TTV reactivation. Leuk Res. 2018 Jul;70:20-24. doi: 10.1016/j.leukres.2018.04.016. Epub 2018 May 2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2014
• Primary Completion (ACTUAL): September 10, 2019
• Study Completion (ACTUAL): September 10, 2019

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 18, 2017
• First Posted (ACTUAL): May 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 7, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: zinc
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C19 Inhibitors; Astringents; Levofloxacin; Ofloxacin; Fluconazole; Acyclovir; Zinc Sulfate
• Other Study ID Numbers: Hematology AOUPisa

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No