UMIN-CTR Clinical Trial

Public title

Autologous peripheral blood stem cell transplantation for Ph+ALL (Auto-Ph17 study)

Acronym

Autologous peripheral blood stem cell transplantation for Ph+ALL (Auto-Ph17 study)

Scientific Title

Autologous peripheral blood stem cell transplantation for Ph+ALL (Auto-Ph17 study)

Scientific Title:Acronym

Autologous peripheral blood stem cell transplantation for Ph+ALL (Auto-Ph17 study)

Region

Japan

Condition

Philadelphia chromosome-positive acute lymphoblastic leukemia

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To evaluate the safety and efficacy of autologous peripheral blood stem cell transplantation for patients with Philadelphia-chromosome positive acute lymphoblastic leukemia who achieved complete molecular remission within 3 chemotherapy regimens.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase I,II

Primary outcomes

Day 100- mortality after transplantation

Key secondary outcomes

1) Day 100- molecular and hematological replase rate.
2) 1 year- molecular and hematological replase rate.
3) 3 year- molecular and hematological replase rate.
4) Day 100- overall survival, event-free survival, relapse rate and non-relapse mortality.
5) 1 year- overall survival, event-free survival, relapse rate and non-relapse mortality.
6) 3 year- overall survival, event-free survival, relapse rate and non-relapse mortality.
7) The proportion of therapy related mortality.
8) The proportion of adverse events in each regimen.
9) Success rate of peripheral blood stem cell harvest.
10) Detection of BCR-ABL chimeric gene in harvested peripheral blood stem cell by real-time quantitative PCR.
11) Safety of peripheral blood stem cell transplantation (the proportion of engraftment and engraftment failure).
12) Cumulative dose of dasatinib during maintenance therapy.
13) Mutation analysis of BCR-ABL chimeric gene in relapsed patients.

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

Peripheral blood stem cell harvest is performed following JALSG Ph+ALL213 C2 regimen (CPM/DNR/VCR/PSL). Peripheral blood stem cell transplantation is performed using LEED regimen (L-PAM/CPM/ETP/DEX). Between 30 and 50 days after transplantation, patients proceed to 12 courses of 4-week dasatinib-based maintenance therapy.

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

55

years-old

<=

Age-upper limit

70

years-old

>=

Gender

Male and Female

Key inclusion criteria

1. Acute lymphoblastic leukemia.
2. BCR/ABL positive.
3. aged >= 55 years and <= 70 years.
4. Newly diagnosed patients.
5. Complete molecular remission was achieved within 3 chemotherapy regimens.
6. ECOG performance status of 0, 1, 2 or 3.
7. Patients must have adequate cardiac, hepatic, renal, and pulmonary functions.
8. Voluntary written consent must be given before enrollment.

Key exclusion criteria

1. Heart insufficiency.
2. Pulmonary fibrosis, interstitial pneumonitis.
3. Uncontrollable diabetes mellitus.
4. Grade 4 infection.
5. HIV antibody positive.
6. HBs antigen positive.
7. Acquired bleeding diathesis.
8. Psychiatric illness.
9. Active another malignancy.
10. Patients who, in the judgment of the investigator, would be inappropriate for entry into this study.

Target sample size

5

Name of lead principal investigator

1st name	Satoshi
Middle name
Last name	Nishiwaki

Organization

Nagoya University Hospital

Division name

Center for Advanced Medicine and Clinical Research

Zip code

466-8560

Address

65 Tsurumai-cho Showa-ku Nagoya, 4668560, Japan

TEL

052(744)-2942

Email

n-3104@med.nagoya-u.ac.jp

Name of contact person

1st name	Satoshi
Middle name
Last name	Nishiwaki

Organization

Nagoya University Hospital

Division name

Center for Advanced Medicine and Clinical Research

Zip code

466-8560

Address

65 Tsurumai-cho Showa-ku Nagoya, 4668560, Japan

TEL

052(744)-2942

Homepage URL

Email

n-3104@med.nagoya-u.ac.jp

Institute

Nagoya University Hospital

Institute

Department

Personal name

Organization

Nagoya University Hospital

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Nagoya University Hospital

Address

65 Tsurumai-cho Showaku, Nagoya

Tel

052(741)-2111

Email

ethics@med.nagoya-u.ac.jp

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

2017

Year

04

Month

17

Day

URL releasing protocol

https://pubmed.ncbi.nlm.nih.gov/29384978/

Publication of results

Published

URL related to results and publications

https://pubmed.ncbi.nlm.nih.gov/37206256/

Number of participants that the trial has enrolled

5

Results

No patient died within 100 days after auto-PBSCT, and no unexpected serious adverse events were observed. Although 1-year event-free survival was 100%, hematological relapse was observed in three patients at a median of 801 days (range, 389-1088 days) after auto-PBSCT. Molecular progressive disease was observed in the other two patients, although they maintained their first hematological remission at the last visit. Auto-PBSCT can be safely performed for Ph+ALL.

Results date posted

2023

Year

05

Month

22

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Between September 2017 and February 2019, five patients were enrolled in this study. The median age at registration was 62 years (range, 59-68), the white blood cell count at diagnosis was 7,100 (range, 600-168,700), and additional chromosomal abnormalities were identified in three patients. Complete molecular response (CMR) was achieved after one course of chemotherapy in three patients and after two courses of chemotherapy in two patients. The median time from diagnosis to CMR was 46 days (range, 43-76 days).

Participant flow

In three of the five patients, the target number of CD34+ positive cells was obtained during one collection regimen. The remaining two patients were also able to collect the required cells during the second collection regimen, and auto-PBSCT was performed in five patients.
One patient developed hematologic relapse after the seventh course of maintenance therapy.
Four patients completed 12 courses of maintenance therapy, after which two had hematologic remission and two had molecular progression.

Adverse events

No patient died up to 100 days after auto-PBSCT. Febrile neutropenia was the most common severe adverse event (grades 3 to 4) during the auto-PBSCT period. No unexpected serious adverse events were observed.
During maintenance therapy, neutropenia and thrombocytopenia were frequently observed as hematological adverse events, but more than half of the cases were grades 1-2. On the other hand, non-hematological adverse events were infrequently observed due to the appropriate dose reduction of dasatinib. All patients were able to continue dasatinib until the planned number of maintenance courses or relapse.

Outcome measures

(Primary endpoint)
Death during 100 days after auto-PBSCT: 0

(Secondary endpoints)
Efficacy Day100 1-year 3-year
Proportion of molecular relapse 0.2 0.2 1
Proportion of hematological relapse 0 0 0.6
OS 100% 100% 75%
EFS 100% 100% 40%
Molecular relapse rate 20% 20% 100%
Hematological relapse rate 0% 0% 60%
NRM 0% 0% 0%

Safety
Proportion of therapy-related death 0
Proportion of adverse events PBSCH PBSCT Maintenance
Hematological, all grade (grade 3-4) 1 (0.8) 1 (1) 1 (0.4)
Non-hematological, all grade (grade 3-4) 1 (0.6) 1 (0.8) 0.6 (0.2)
Success rate of PBSCH 　 　 　
Overall 100%
PBSCH1 60%
Detection of BCR-ABL in harvested PBSC 0 (0/1)
Proportion of engraftment failure 0
Ratio of actual dose of dasatinib to planned dose during maintenance therapy, median (range) 0.91 (0.2-1)
Mutation analysis of BCR-ABL at relapse 0 (0/2)

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

04

Month

17

Day

Date of IRB

2017

Year

06

Month

13

Day

Anticipated trial start date

2017

Year

06

Month

13

Day

Last follow-up date

2022

Year

03

Month

19

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

03

Month

07

Day

Last modified on

2023

Year

06

Month

20

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030357