Observational Study of the Combination of Post-transplant High Dose Cyclophosphamide, Tacrolimus and Mycophenolate Mofetil for the Prevention of Acute Graft-versus-Host Disease in Patients Eligible to Allogeneic Hematopoietic Stem Cell Transplant

An Observational Retrospective/Prospective Study of the Combination of Post-transplant High Dose Cyclophosphamide, Tacrolimus and Mycophenolate Mofetil for the Prevention of Acute Graft-versus-Host Disease in Patients Eligible to Allogeneic Hematopoietic Stem Cell Transplant Using Peripheral Blood Stem Cells (PBSC) From Unrelated or Related, HLA-identical or Partially Mismatched Donors

This observational study is proposed to observe the effect of high-dose, post-transplantation cyclophosphamide after a T cell-replete, HLA-matched PBSC graft from an HLA-identical or mismatched donor.

Study Overview

• Status: Unknown
• Conditions: Hematological Malignancies

Detailed Description

Allogeneic hematopoietic cell transplantation (HCT) remains the only curative approach for many hematological malignancies. In allogeneic HCT the donor immune system through the donor lymphocytes exerts both a beneficial and detrimental effect. Graft versus host disease (GVHD) represents the major complication and cause of mortality of allogeneic HCT. The principal aim that clinical transplant research must accomplish in the next years is to elaborate a transplant strategy devoid of any GVHD but still capable of generating, through donor lymphocytes, the graft versus tumor effect (GVT). The most used GVHD prophylaxis regimen remains the association of a calcineurin-inhibitor (CNIs) for six months and four low-doses of methotrexate (MTX) but the long length prophylaxis impacts on the process of post-transplant immune reconstitution slowing it down and exposing patients to a high risk of developing severe infections. The use of post-transplant cyclophosphamide looks the most promising among the new approaches to GVHD control. The study design is an observational retrospective/prospective Study in Patients Eligible to Allogeneic Hematopoietic Stem Cell Transplant using Peripheral Blood Stem Cells (PBSC) from unrelated or related, HLA-identical or partially mismatched donors. In case of unrelated donor, donor selection will be done accordingly to Italian Bone Marrow Donor Registry (IBMDR). This protocol and the treatment plan outlined below are limited to the plan or GVHD prevention.

The treatment plan for all patients including pre-conditioning therapy, TBI/chemotherapy, central nervous system prophylaxis and other planned therapies, is described in the primary transplant protocols which the patient has been assigned by the investigational site.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• Italy
  • Candiolo, Italy, 10060
    • Recruiting
    • Fondazione del Piemonte per l'Oncologia
    • Contact: Luisa Gioeni, PharmD; Phone Number: 3959 +39011993; Email: luisa.gioeni@ircc.it
    • Sub-Investigator: Fabrizio Carnevale Schianca, MD
    • Sub-Investigator: Daniela Caravelli, MD
    • Sub-Investigator: Dario Sangiolo, MD
    • Sub-Investigator: Susanna Gallo, MD
    • Sub-Investigator: Valentina Coha, MD
    • Sub-Investigator: Giovanni Grignani, MD
    • Sub-Investigator: Delia Rota Scalabrini, MD
    • Sub-Investigator: Marco Fizzotti, MD
  • Torino, Italy, 10126
    • Not yet recruiting
    • Ospedale Regina Margherita
    • Contact: Massimo Berger, MD; Phone Number: 5360 +39011.313; Email: massimoberger@gmail.com
    • Principal Investigator: Franca Fagioli, MD
    • Sub-Investigator: Elena Vassallo, MD
    • Sub-Investigator: Massimo Berger, MD
    • Sub-Investigator: Francesca Nesi, MD
    • Sub-Investigator: Paola Quarello, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Hematological Malignancies Eligible to Allogeneic Hematopoietic Stem Cell Transplant using Peripheral Blood Stem Cells (PBSC) from unrelated or related, HLA-identical or partially mismatched donors

Description

Inclusion Criteria:

1. Patient is scheduled for transplant of 'mobilized' peripheral blood stem cells (PBSC) from a genotypically HLA-unrelated or related identical or partially mismatched stem cell donor.
2. Patient is ≥ 18 years and ≤ 65 years of age.

3. Diagnosis of malignancy. Patients will be divided on the basis of their disease in low risk and high risk patients.

   High risk diseases: AML > CR1, ALL > CR1, CML in CP #2, AP or BP, non-Hodgkin's lymphoma > CR2, Hodgkin's lymphoma > CR2, other patient with refractory malignancy Low risk: multiple myeloma (all patients), AML in CR1, myelodysplastic syndrome beyond RA (including CMML) and ALL in CR1.

4. Patient or legal guardian has signed/dated the informed consent form.
5. Female patients must have a negative pregnancy test (blood or urine) unless they are prepuberal or surgically sterile.
6. Estimated Creatinine Clearance ≥ 60 mL/min at time of consent.
7. Total bilirubin is ≤ 1.5 times the upper limit of normal at time of consent.
8. SGOT and SGPT are ≤ 2.0 times the upper limit of normal at time of consent.

Exclusion Criteria:

1. Patient > 65 years of age
2. Patient has not signed/dated the informed consent form.
3. Patient is receiving a T-cell depleted hematopoietic stem cell graft.
4. Pregnant or lactating women
5. Patient has an acute pulmonary infection suspected on the basis of abnormal chest x-ray.
6. Patient has an active systemic infection not controlled with anti-microbial therapy.
7. Patient is a known carrier of any of the Human Immune Deficiency Viruses (HIV-1 or others).

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of the observed GVHD rate and infections	Evaluations through day 100 after transplantation will be performed with: Complete blood count (CBC), including differential and platelet count per standard practice guidelines at the performance site.; Blood chemistries: including sodium, potassium, chloride, bicarbonate (HCO3) or total carbon dioxide (CO2), glucose, blood urea nitrogen (BUN), creatinine, calcium, magnesium, phosphorus, total bilirubin, total protein, albumin, serum glutamic oxaloacetic transaminase (SGOT), lactic dehydrogenase (LDH), alkaline phosphatase per standard practice guidelines at the performance site. Tacrolimus whole blood concentrations weekly starting on day 6. CMV surveillance, Aspergillus surveillance will be performed per standard practice guidelines at the performance site. Evaluations after 100 days post-transplant will be completed per standard practice guidelines at each performance site.	100 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	To determine the overall survival at 1 years (OS)	1 years
Progression-free survival	To determine progression-free survival at 1 years (PFS)	1 years

Collaborators and Investigators

• Sponsor: Fondazione del Piemonte per l'Oncologia
• Investigators: Principal Investigator: Massimo Aglietta, md, Fondazione del Piemonte per l'Oncologia; Study Chair: Franca Fagioli, MD, Ospedale Regina Margherita; Study Chair: Fabrizio Carnevale-Schianca, MD, Fondazione del Piemonte per l'Oncologia

Publications and helpful links

General Publications

• Carnevale-Schianca F, Caravelli D, Gallo S, Becco P, Paruzzo L, Poletto S, Polo A, Mangioni M, Salierno M, Berger M, Pessolano R, Saglio F, Gottardi D, Rota-Scalabrini D, Grignani G, Fizzotti M, Ferrero I, Frascione PMM, D'Ambrosio L, Gaidano V, Gammaitoni L, Sangiolo D, Saglietto A, Vassallo E, Cignetti A, Aglietta M, Fagioli F. Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Governs GVHD and Immunosuppression Need, Reducing Late Toxicities in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors. J Clin Med. 2021 Mar 11;10(6):1173. doi: 10.3390/jcm10061173.
• Carnevale-Schianca F, Caravelli D, Gallo S, Coha V, D'Ambrosio L, Vassallo E, Fizzotti M, Nesi F, Gioeni L, Berger M, Polo A, Gammaitoni L, Becco P, Giraudo L, Mangioni M, Sangiolo D, Grignani G, Rota-Scalabrini D, Sottile A, Fagioli F, Aglietta M. Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors. Biol Blood Marrow Transplant. 2017 Mar;23(3):459-466. doi: 10.1016/j.bbmt.2016.12.636. Epub 2016 Dec 27.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): January 1, 2018

Study Registration Dates

• First Submitted: November 21, 2014
• First Submitted That Met QC Criteria: November 21, 2014
• First Posted (Estimate): November 25, 2014

Study Record Updates

• Last Update Posted (Actual): September 5, 2017
• Last Update Submitted That Met QC Criteria: September 1, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Graft vs Host Disease
• Other Study ID Numbers: HDCTX 2013

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