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

NCT ID: NCT02300571

Last Updated: 2017-09-05

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2018-01-31

Brief Summary

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.

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.

Conditions

Hematological Malignancies

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: OTHER

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione del Piemonte per l'Oncologia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Massimo Aglietta, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione del Piemonte per l'Oncologia

Franca Fagioli, MD

Role: STUDY_CHAIR

Ospedale Regina Margherita

Fabrizio Carnevale-Schianca, MD

Role: STUDY_CHAIR

Fondazione del Piemonte per l'Oncologia

Locations

Fondazione del Piemonte per l'Oncologia

Candiolo, , Italy

Site Status: RECRUITING

Ospedale Regina Margherita

Torino, , Italy

Site Status: NOT_YET_RECRUITING

Countries

Italy

Central Contacts

Fabrizio Carnevale-Schianca, MD

Role: CONTACT

fabrizio.carnevale@ircc.it

+39011993 ext. 3623

Daniela Caravelli, MD

Role: CONTACT

daniela.caravelli@ircc.it

+39011993 ext. 3623

Facility Contacts

Luisa Gioeni, PharmD

Role: primary

luisa.gioeni@ircc.it

+39011993 ext. 3959

Massimo Berger, MD

Role: primary

massimoberger@gmail.com

+39011.313 ext. 5360

References

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.

Reference Type: DERIVED

PMID: 33799685 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28039079 (View on PubMed)

Other Identifiers

HDCTX 2013

Identifier Type: -

Identifier Source: org_study_id