UMIN-CTR Clinical Trial

Public title

A Phase II trial of haploidentical transplantation with high dose, post-transplantation cyclophosphamide.

Acronym

JSCT-Haplo13

Scientific Title

A Phase II trial of haploidentical transplantation with high dose, post-transplantation cyclophosphamide.

Scientific Title:Acronym

JSCT-Haplo13

Region

Japan

Condition

ALL,AML,MDS,CML,NHL,MM

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

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

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.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Junichi Sugita

Organization

Hokkaido University Hospital

Division name

Department of Hematology

Zip code

Address

060-8638 Sappor

TEL

011-706-7214

Email

sugita@med.hokudai.ac.jp

Name of contact person

1st name
Middle name
Last name	JSCT

Organization

JSCT

Division name

Haplo13 DC

Zip code

Address

104-0031

TEL

03-6225-2025

Homepage URL

Email

jsct-office@umin.ac.jp

Institute

JSCT

Institute

Department

Personal name

Organization

Resarch Foundation for Community Medicine

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2013

Year

03

Month

26

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

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.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2013

Year

03

Month

26

Day

Date of IRB

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

Other related information

Registered date

2013

Year

03

Month

26

Day

Last modified on

2018

Year

03

Month

21

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012076