UMIN-CTR Clinical Trial

Unique ID issued by UMIN C000000161
Receipt number R000000231
Scientific Title Phase I/II study of adoptive immunotherapy using predetermined minor histocompatibility antigen-specific cytotoxic T cells for patients with high-risk leukemia that relapsed following allogeneic hematopoietic stem cell transplantation.
Date of disclosure of the study information 2005/09/12
Last modified on 2005/09/12 00:34:20

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Basic information

Public title

Phase I/II study of adoptive immunotherapy using predetermined minor histocompatibility antigen-specific cytotoxic T cells for patients with high-risk leukemia that relapsed following allogeneic hematopoietic stem cell transplantation.

Acronym

Cellular adoptive immunotherapy targeting predetermined minor histocompatibility antigens for the treatment of patients with relapsed leukemia following transplantation.

Scientific Title

Phase I/II study of adoptive immunotherapy using predetermined minor histocompatibility antigen-specific cytotoxic T cells for patients with high-risk leukemia that relapsed following allogeneic hematopoietic stem cell transplantation.

Scientific Title:Acronym

Cellular adoptive immunotherapy targeting predetermined minor histocompatibility antigens for the treatment of patients with relapsed leukemia following transplantation.

Region

Japan


Condition

Condition

1) RAEB, CMML 2) AML or ALL in induction failure or beyond first remission 3) Ph/p190-positive ALL at any stage 4) imatinib-resistant CML

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO


Objectives

Narrative objectives1

Phase I/II study to evaluate the safety and efficacy of adoptive immunotherapy using cytotoxic T cells specific for predetermined minor histocompatibility antigens in treating patients with high-risk leukemia following allogeneic hematopoietic stem cell transplantation

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1


Trial characteristics_2


Developmental phase

Phase I,II


Assessment

Primary outcomes

1) Determine the toxicity including grade II or more acute GVHD from the initiation of T cell infusion to 2 weeks after the last infusion and extensive chronic GVHD. 2) Determine the non-hematological toxicity (grade 3 or 4) from the initiation of T cell infusion to 2 weeks after the last infusion.

Key secondary outcomes

1) Determine the CR rate from the initiation of T cell infusion to 2 weeks after last infusion. 2) Determine the persistence and kinetics of transfused T cells in vivo from the initiation of T cell infusion to 2 weeks after last infusion. 3) Determine the T cell number that can be infused safely.


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

Maneuver

Interventions/Control_1

Upon relapse, immunosuppressive drugs are withdrawn. If necessary, cytoreductive chemotherapy may be administered before adoptive immunotherapy. In the absence of unacceptable toxicity due to cessation of immunosuppressive drugs or chemotherapy, patients receive weekly CTL clone infusion 5 times. Initial dose is 3 million cells/m2. Cell numbers are escalated by 3.2 times each infusion. If anti-leukemic effect is observed, dose escalation is suspended.

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

18 years-old <=

Age-upper limit

65 years-old >=

Gender

Male and Female

Key inclusion criteria

1) Patients diagnosed of one of the following type of leukemia: (a) RAEB, CMML, (b) AML or ALL in induction failure or beyond first remission, (c) Ph/p190-positive ALL at any stage, (d) imatinib-resistant CML 2) Aged 18 to 65 years 3) Sufficient organ function 4) ECOG PS 0-2 at time of enrollment 5) Patients receiving their first transplantation 6) Donor-patient pairs possessing appropriate disparity in predetermined minor histocompatibility antigens and restriction HLA alleles (i.e., BCL2A1/A24, HA-1/A*0201). 7) Written informed consent from the patients or their legal guardians (under 20 years old). 8) No other complications not suitable for transplantation. 9) Eligibility criteria at time of CTL infusion: (a) Patients with relapse at least 60 days after transplantation. (b) CTL clones must have been generated and have completed QC testing before treatment. (c) Relapsed leukemia as clearly defined by 1 or more of the following: morphologic relapse, cytogenetic relapse, molecular relapse. (d) Patients with >= grade III acute GVHD after transplantation. Patients with >= grade II acute GVHD or extensive chronic GVHD after cessation of immunosuppressive drugs other than maintenance dose of steroid. (e) No non-hematopoietic organ toxicity >= grade 3 one week prior to CTL infusion (NCI-CTC). (f) Neutrophil counts >= 200/ul at least 10 days after completion of cytoreductive chemotherapy.

Key exclusion criteria

1) CNS involvement or uncontrollable extramedullary disease. 2) Severe infections (including active tuberculosis) or double cancer 3) Patients with organ toxicity as follows: (a) T.Bil >= 1.5 mg/dl, (b) GOT, GPT >= 2.5 x N (upper normal limit of individual institutions), (c) serum creatine >= 1.5 x N, 24-h Ccr =< 60 ml/min, (d) PaO2 < 60 mmHg, (e) ejection fraction <50%, (f) abnormal ECG (ischemic change or arrhythmia requiring treatment) 4) Uncontrolable HT 5) One of the following: positive HBs antigen, seropositive to HCV, seropositive to HIV, seropositive to HTLV-1, seropositive to STS 6) Patients treated with major tranquilizer or antidepressant 7) Patients inappropriate for transplantation with reasons other than above.

Target sample size

30


Research contact person

Name of lead principal investigator

1st name
Middle name
Last name Yoshiki Akatsuka, M.D.,Ph.D

Organization

Aichi Cancer Center

Division name

Division of Immunology, Department of Cell Therapy and Hematology

Zip code


Address

1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, JAPAN

TEL

052-762-6111

Email



Public contact

Name of contact person

1st name
Middle name
Last name Yoshiki Akatsuka, M.D.,Ph.D

Organization

Aichi Cancer Center

Division name

Division of Immunology, Department of Cell Therapy and Hematology

Zip code


Address

1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, JAPAN

TEL

052-762-6111

Homepage URL


Email



Sponsor or person

Institute

Aichi Cancer Center

Institute

Department

Personal name



Funding Source

Organization

Ministry of Health, Labour and Welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan


Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization


Address


Tel


Email



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

2005 Year 09 Month 12 Day


Related information

URL releasing protocol


Publication of results

Unpublished


Result

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



Progress

Recruitment status

Date of protocol fixation

2003 Year 08 Month 26 Day

Date of IRB


Anticipated trial start date

2003 Year 10 Month 01 Day

Last follow-up date

2007 Year 09 Month 01 Day

Date of closure to data entry


Date trial data considered complete


Date analysis concluded



Other

Other related information



Management information

Registered date

2005 Year 09 Month 12 Day

Last modified on

2005 Year 09 Month 12 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000231


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name