UMIN-CTR Clinical Trial

Public title

HLA-haploidentical allogeneic stem cell transplantation for refractory hematopoietic diseases

Acronym

HLA-haploidentical allogeneic stem cell transplantation for refractory hematopoietic diseases

Scientific Title

HLA-haploidentical allogeneic stem cell transplantation for refractory hematopoietic diseases

Scientific Title:Acronym

HLA-haploidentical allogeneic stem cell transplantation for refractory hematopoietic diseases

Region

Japan

Condition

Acute myeloid leukemia(AML)
Acute lymphoblastic leukemia (ALL)
Secondary acute myelogenous leukemia
Chronic myeloid leukemia (CML)
Myelodysplastic syndrome (MDS)

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To assess the safety and efficacy of HLA-haploidentical allogeneic stem cell transplantation from related donor for patients with poor-prognosis leukemia and myelodysplastic syndrome or patient with refractory leukemia and myelodysplastic syndrome lacking an HLA serological identical or a single antigen mismatched related donor who need urgent stem cell transplantation due to disease progression.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Engraftment rate

Key secondary outcomes

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

Fludarabine(15mg/square meter of body surface area twice a day for 2 days and 30mg/square meter once a day for 4 days), cytarabine(2g/square meter twice a day for 2 days), buslufan(0.8mg/kg 4 times a day for 4 days) and ATG(2mg/kg per day for 2days) is used as a conditioning regimen. (If a patient has a history of using Busulfan as a conditioning regimen of previous transplantation, Melphalan(100mg/ square meter per day for 1 day) is used instead of Busulfan.) Cyclophosphamide (25mg/kg)is used on day3, 4 after the graft infusion. The donor source is peripheral blood stem cell. Patients receive cotinuous intravenous tacrolimus (0.03mg/kg/day) and mycophenolate mofetil 3000mg/day from day4 after hematopoietic stem cell transplantation.

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

70

years-old

>

Gender

Male and Female

Key inclusion criteria

1) Patients with refractory leukemia or MDS lacking an HLA-identical or single-antigen mismatched related donor, who need an urgent allogeneic transplant but are ineligible for unrelated donor from marrow donor registry in a timely fashion due to rapid disease progression, or patients with refractory leukemia or MDS considered incurable by only conventional chemotherapy, who have no HLA-identical related or HLA-single-antigen mismatched related donor.
2) Patients without a HLA-haploidentical donor of family member or relative
3) >= 15 and <= 70 years old
4) ECOG PS 0-1
5) Normal function of major organ
6) Informed consent

7) Patients who in need of an urgent allogeneic transplant
a) De novo AML and ALL: refractory to first induction therapy or refractory to chemotherapy after relapse
b) CML in AP or BC: refractory to TKIs including imatinib, dasatinib and nilotinib
c) Secondary acute leukemia following MDS: refractory to first induction therapy
d) Patients with AML, ALL, CML or secondary acute leukemia who relapsed after allogeneic transplant and failed to achieve CR
8) Patients who have indication for allogeneic transplant due to unfavorable prognosis but lack a suitable related donor
a) Patients with de novo AML in CR with unfavorable chromosome abnormality including del(5q)/-5, -7/del(7q), abn 3q, 9q, 11q, 20q, 21q, 17q, t(6;9), t(9;22) or complex karyotype
b) Patients with de novo AML in CR with normal karyotype and FLT3-ITD mutation
c) Patients with ALL in 1CR who have following poor prognostic factors
i) t(9;22) or t(4;11)
ii) >= 35 years at diagnosis
iii) WBC count of more than 30000/uL for B- ALL, or more than 100000/uL for T-ALL at diagnosis
d) AML, ALL in CR state except for 1CR
e) CML in CR state except for 1CR
f) Secondary leukemia following MDS, or patients with RAEB-1, 2
g) Patients with AML, ALL, or secondary leukemia in CR state or CML in CP who relapsed after allogeneic transplant

Key exclusion criteria

1) Major organ dysfunction
a) Total bilirubin: >= 2.0mg/dl
b) Serum creatinine: >= 2.0mg/dl
c) Ejection fraction: < 50 %
d) Pulmonary function test: %VC <40%, FEV1.0% <50% or SaO2 <90% on room air
e) AST or ALT >= 3 x UNL
2) Uncontrolled active infection
3) Uncontrolled CNS invasion
4) Poorly controlled insulin-treated diabetes mellitus
5) Poorly controlled hypertension
6) Patients with a severe complication including heart failure, coronary failure, acute myocardial infarction within the last 3 months, liver cirrhosis and interstitial pneumonia
7) Pregnant, nursing or possible fertile woman
8) Patients with severe mental disorder who are likely to unable to participate in the study
9) A history of hypersensitivity or allergy to any drugs in conditioning regimen of this transplant
10) HIV antibody positivity
11) No indication for this study judged by physician in charge.
(Note: HBs antigen positivity and HCV antibody positivity is not excluded.)

Target sample size

17

Name of lead principal investigator

1st name
Middle name
Last name	Masayuki Hino

Organization

Osaka City University, Graduate School of Medicine

Division name

Hematology

Zip code

Address

1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan. 545-8585

TEL

06-6645-3881

Email

hinom@med.osaka-cu.ac.jp

Name of contact person

1st name
Middle name
Last name	Mika Nakamae

Organization

Osaka City University, Graduate School of Medicine

Division name

Hematology

Zip code

Address

1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan. 545-8585

TEL

06-6645-3881

Homepage URL

Email

crc-hematology@med.osaka-cu.ac.jp

Institute

Hematology, Osaka City University, Graduate School of Medicine

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

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

2009

Year

06

Month

12

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

Results

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

Completed

Date of protocol fixation

2009

Year

06

Month

12

Day

Date of IRB

Anticipated trial start date

2009

Year

12

Month

25

Day

Last follow-up date

2015

Year

02

Month

28

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2009

Year

06

Month

11

Day

Last modified on

2016

Year

03

Month

28

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002370