Clinical trial NCT02294552: Post-transplantation Cyclophosphamide as GVHD Prophylaxis After HSCT
Official title: High-dose Post-transplantation Cyclophosphamide as Graft Versus-host Disease Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphoid Leukemia
Lymphoma
Myelodysplastic Syndromes
Chronic Lymphocytic Leukemia
Immune System Diseases
Keywords: Cyclophosphamide
Leukemia
Lymphoma
Myelodysplastic Syndromes
Chronic Lymphocytic Leukemia
Immunosuppressive Agents
Immune System Diseases
Busulfan
Fludarabine
Tacrolimus
Mycophenolate mofetil
Antineoplastic Agents, Alkylating
Myeloablative Agonists
Hematopoietic Stem Cell Transplantation
Allogeneic
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2014-11-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the efficacy of high-dose post-transplantation cyclophosphomide as graft-versus-host disease (GVHD) prophylaxis after allogeneic stem cell transplantation in patients with different risk of GVHD. The risk-adapted strategy involves using single-agent cyclophosphomide in recipients of matched bone marrow graft, and combining cyclophosphomide with tacrolimus and mycophenolate mofetil in recipients of matched peripheral blood stem cells and mismatched bone marrow.


Eligibility criteria: Inclusion Criteria:

* Patients must have an indication for allogeneic hematopoietic stem cell transplantation
* Signed informed consent
* Patients with a donor available. The donor and recipient must be identical at at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is required for related donor. A minimum match of 8/10 is required for unrelated donor.
* No second tumors
* No severe concurrent illness

Exclusion Criteria:

* Moderate or severe cardiac dysfunction, left ventricular ejection fraction \<50%
* Moderate or severe decrease in pulmonary function, FEV1 \<70% or DLCO\<70% of predicted
* Respiratory distress \>grade I
* Severe organ dysfunction: AST or ALT \>5 upper normal limits, bilirubin \>1.5 upper normal limits, creatinine \>2 upper normal limits
* Creatinine clearance \< 60 mL/min
* Uncontrolled bacterial or fungal infection at the time of enrollment
* Requirement for vasopressor support at the time of enrollment
* Karnofsky index \<30%
* Pregnancy
* Somatic or psychiatric disorder making the patient unable to sign informed consent

Primary outcomes:
measure: Incidence of acute and chronic GVHD, requiring treatment
timeFrame: 365 days
Secondary outcomes:
measure: Incidence of primary graft failure
timeFrame: 60 days
measure: Non-relapse mortality analysis
timeFrame: 365 days
measure: Overall survival analysis
timeFrame: 365 days
measure: Event-free survival analysis
timeFrame: 365 days
measure: Relapse rate analysis
timeFrame: 365 days
measure: Toxicity based NCI CTC grades
timeFrame: 100 days
measure: Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
timeFrame: 100 days
Other outcomes:
Locations:
city: Saint-Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St. Petersburg
Study officials:
affiliation: First Pavlov State Medical University of St. Petersburg
name: Boris V Afanasyev, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moiseev IS, Pirogova OV, Alyanski AL, Babenko EV, Gindina TL, Darskaya EI, Slesarchuk OA, Bykova TA, Chukhlovin AB, Pevtcov DE, Bondarenko SN, Afanasyev BV. Risk-adapted GVHD prophylaxis with post-transplantation cyclophosphamide in adults after related, unrelated, and haploidentical transplantations. Eur J Haematol. 2018 May;100(5):395-402. doi: 10.1111/ejh.13030. Epub 2018 Mar 1.