Post-transplantation Cyclophosphamide as GVHD Prophylaxis After HSCT

Ivan S Moiseev

Status and phase: Completed; Phase 2

Conditions: Acute Lymphoid Leukemia; Immune System Diseases; Lymphoma; Chronic Lymphocytic Leukemia; Myelodysplastic Syndromes; Acute Myeloid Leukemia

Treatments: Drug: Busulfan; Drug: Tacrolimus; Procedure: Allogeneic hematopoietic stem cell transplantation; Drug: Cyclophosphamide; Drug: Mycophenolate mofetil; Drug: Fludarabine monophosphate

Study type: Interventional

Funder types: Other

Identifiers

NCT02294552

PTCy-2014

Details and patient eligibility

About

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.

Enrollment: 200 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 3 patient groups

Matched bone marrow graft

Experimental group

Description:

Days -8 through -4: Busulfan 1 mg/kg po qid x 4 days Days -3 through -2: Cyclophosphamide 50mg/kg/day iv x 2 days Or Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv

Treatment:

Procedure: Allogeneic hematopoietic stem cell transplantation

Drug: Busulfan

Drug: Fludarabine monophosphate

Drug: Cyclophosphamide

Matched peripheral blood stem cells graft

Experimental group

Description:

Days -8 through -4: Busulfan 1 mg/kg po qid x 4 days Days -3 through -2: Cyclophosphamide 50mg/kg/day iv x 2 days Or Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days +5 through +120: Tacrolimus 0.03 mg/kg/day with further correction by concentration

Treatment:

Procedure: Allogeneic hematopoietic stem cell transplantation

Drug: Mycophenolate mofetil

Drug: Busulfan

Drug: Tacrolimus

Drug: Fludarabine monophosphate

Drug: Cyclophosphamide

Mismatched peripheral blood stem cells or bone marrow graft

Experimental group

Description:

Days -8 through -4: Busulfan 1 mg/kg po qid x 4 days Days -3 through -2: Cyclophosphamide 50mg/kg/day iv x 2 days Or Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv Days +5 through +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days Days +5 through +120: Tacrolimus 0.03 mg/kg/day with further correction by concentration

Treatment:

Procedure: Allogeneic hematopoietic stem cell transplantation

Drug: Mycophenolate mofetil

Drug: Busulfan

Drug: Tacrolimus

Drug: Fludarabine monophosphate

Drug: Cyclophosphamide