UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A Phase II trial of haploidentical transplantation with high dose, post-transplantation cyclophosphamide.
Title of the study (Brief title)	JSCT-Haplo13
Region	Japan

Condition
Condition	ALL,AML,MDS,CML,NHL,MM
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	The objective of this study is to assess the efficacy and safety of haploidentical transplantation with high dose, post-transplantation cyclophosphamide in patients who have no HLA-matched or 7/8 matched, related or unrelated donor.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Transplant-related mortality at 100 days.
Key secondary outcomes	1. Overall survival, progression-free survival, relapse at 100 days. 2. Overall survival, progression-free survival, Relapse, Transplant-related mortality at 1 year. 3. Neutrophil and platelet recovery. 4. Graft failure. 5. Full donor chimerism. 6. Acute Graft-versus-Host Disease. 7. Chronic Graft-versus-Host Disease. 8. Infection 9. Grade 3-4 non-hematologic toxicity within 100 days.

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	The preparative regimen will consist of : Fludarabine 30mg/m2 IV Days -6, -5, -4, -3, -2 Cyclophosphamide 14.5mg/kg IV Days -6, -5 Busulfan 3.2mg/kg IV Days -3, -2 Total body irradiation (TBI) 2Gy Day -1 Day 0 will be the day of infusion of non-T-cell depleted peripheral blood stem cells The GVHD prophylaxis regimen will consist of : Cyclophosphamide 50mg/kg IV days 3, 4 Tacrolimus IV beginning Day 5 with dose adjusted to maintain a level of 5-15 ng/ml
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	15 years-old <=
Age-upper limit	65 years-old >=
Gender	Male and Female
Key inclusion criteria	1. Patients who have hematologic malignancies and who are eligible for allogeneic stem cell transplantation. 2. Age: 15-65 years old. 3. 2nd CR or subsequent CR, non CR. 1st CR as defined at least one of the following: a) Acute lymphoblastic leukemia Poor risk as defined by NCCN guidelines b) Acute Myelogenous Leukemia Greater than 1 cycle of induction therapy required to achieve remission High risk as defined by NCCN guidelines Monosomal karyotype ckit mutations with t(8;21), inv(16), t(16;16) t(7;11)(p15;p15) Preceding myelodysplastic syndrome c) Myelodysplastic syndrome high, very high as defined by WHO classification-based Prognostic Scoring System Patients who have receive ten units or more platelet transfusions per week, or two units or more RBC transfusions per month. 4. Patients who have prior allogeneic or autologous hematopoietic stem cell transplant are not excluded. 5. Performance status: 0-2 6. Patients with adequate physical function (Cardiac, Hepatic, Renal, Pulmonary). 7. Patients who have no HLA-matched or 7/8 matched, related donor. 8. Patients who have no HLA-matched or 7/8 matched, related donor. 9. Patients who give written informed consent to participate in the study. 10. Patients who are expected to live for 3 months or more.
Key exclusion criteria	1. Patients who are positive for HBs antigen, HCV antibody, or HIV antibody. 2. Patients with active other malignancies. 3. Patients with active infectious disease. 4. Women who are pregnant, of childbearing potential, or lactating. 5. Patients who experienced serious hypersensitivity or anaphylaxis to cyclophosphamide, fludarabine, tacrolimus, mycophenolate mofetil. 6. Positive anti-donor HLA antibody. 7. Patients who need chemotherapy within 13 days before transplantation. 8. Patients who are not eligible for this study at the discretion of the investigator.
Target sample size	20

Research contact person
Name of lead principal investigator	Junichi Sugita
Organization	Hokkaido University Hospital
Division name	Department of Hematology
Address	060-8638 Sappor
TEL	011-706-7214
Email	sugita@med.hokudai.ac.jp

Public contact
Name of contact person	JSCT
Organization	JSCT
Division name	Haplo13 DC
Address	104-0031
TEL	03-6225-2025
Homepage URL
Email	jsct-office@umin.ac.jp

Sponsor
Institute	JSCT
Institute
Department

Funding Source
Organization	Resarch Foundation for Community Medicine
Organization
Division
Category of Funding Organization	Non profit foundation
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2013 Year 03 Month 26 Day

Progress
Recruitment status	Main results already published
Date of protocol fixation	2013 Year 03 Month 26 Day
Anticipated trial start date	2013 Year 05 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Published
URL releasing results
Results	Allogeneic hematopoietic stem cell transplantation (allo-SCT) using post-transplant cyclophosphamide (PTCy) is increasingly performed. We conducted a multicenter phase II study to evaluate the safety and efficacy of PTCy-based HLA-haploidentical peripheral blood stem cell transplantation (PTCy-haploPBSCT) after busulfan-containing reduced-intensity conditioning. Thirty-one patients were enrolled; 61% patients were not in remission and 42% patients had a history of prior allo-SCT. Neutrophil engraftment was achieved in 87% patients with a median of 19 days. The cumulative incidence of grades II to IV and III to IV acute graft-versushost disease (GVHD) and chronic GVHD at 1 year were 23%, 3%, and 15%, respectively. No patients developed severe chronic GVHD. Day 100 nonrelapse mortality (NRM) rate was 19.4%. Overall survival, relapse, and disease-free survival rates were 45%, 45%, and 34%, respectively, at 1 year. Subgroup analysis showed that patients who had a history of prior allo-SCT had lower engraftment, higher NRM, and lower overall survival than those not receiving a prior allo-SCT. Our results suggest that PTCy-haploPBSCT after busulfan-containing reduced-intensity conditioning achieved low incidences of acute and chronic GVHD and NRM and stable donor engraftment and low NRM, particularly in patients without a history of prior allo-SCT.
Other related information

Management information
Registered date	2013 Year 03 Month 26 Day
Last modified on	2018 Year 03 Month 21 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012076