Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia (2015)

Terminated

• Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Interventions: Procedure: AlloHCT for Young/MUD&FMD; Procedure: AlloHCT for Old/MSD; Procedure: AlloHCT for Young/MSD; Procedure: AlloHCT for Old/MUD&FMD

• Registration Number: NCT02428517
• Lead Sponsor: Asan Medical Center

Brief Summary

This study is a prospective multicenter observational study to evaluate the feasibility and the efficacy of the conditioning regimens which are modified by the donor differences and the age of recipients among patients who will receive allogeneic hematopoietic stem cell transplantation in their 1st or 2nd hematologic complete remission (CR).

Detailed Description

Allogeneic hematopoietic cell transplantation (AlloHCT) is recommended as a post-remission therapy for patients with adult ALL, and reduced intensity conditioning has been tried to decrease treatment-related mortality (TRM) rate.

Recent results showed that reduced intensity conditioning can be safely and effectively used for alloHCT of adult patients with ALL. However, the reduced intensity conditioning (RIC) can increase the possibilities of hematologic relapse, especially due to the reduced anti-leukemic effect. Another challenge in performing alloHCT for ALL is the donor availability - the limited availability of matched sibling donor (MSD) and well-matched unrelated donor (WMUD) forces us to find the feasibility of alternative donors such as partially-matched unrelated donor (PMUD) or haploidentical familial donor (familial mismatched donor, FMD).

The previous study (NCT0137764) which the investigators performed showed that the use of RIC and alternative donor was feasible. However, the incidence of relapse was slightly higher among patients who received RIC when the investigators analyzed the interim analysis results. Especially, the graft-versus-host disease (GVHD) incidence was relatively higher among patients who received alloHCT from MSD, and the investigators think that the addition of antithymocyte globulin will reduce the incidence of GVHD for these patients.

In this study, the dose of busulfan will be increased when the recipients are below 55 years old, irrespective of donor type. The investigators will also define the partially matched donor exactly and find the feasibility of PMUD and FMD again. Another endpoint for this study is to find out whether the addition of antithymocyte globulin may be helpful in preventing the GVHD incidence for patients who received alloHCT from MSD without increasing the chance of hematologic relapse.

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2015-04-21
• Study First Submitted QC: 2015-04-23
• Study First Posted: 2015-04-28
• Primary Completion: 2016-07
• Study Completion: 2016-07
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-19
• Last Update Posted: 2018-07-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Patients who has been previously diagnosed as one of the following disease;

  • Acute lymphoblastic leukemia
  • Biphenotypic acute leukemia with Philadelphia-positive chromosome or gene translocation

• Patients whose disease status is one of the following;

  • First hematologic complete remission (HCR1)
  • Second hematologic complete remission (HCR2)

• 15 years of age and over.

• With a suitable donor (matched sibling, well-matched unrelated, partially-matched unrelated, and haploidentical familial donor)

• Adequate cardiac function (EF>45% via cardiac scan or EchoCG)

• European Clinical Oncology Group (ECOG) performance status ≥grade 2 or Karnofsky scale >60% at the time of screening

• All patients give written informed consent according to guidelines at institution's committee on human research.

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Exclusion Criteria

• Acute lymphoblastic leukemia L3 type (Burkitt leukemia/lymphoma)
• Biphenotypic acute leukemia without BCR-ABL1 translocation
• Lymphoblastic lymphoma (bone marrow blast count is below 20% of mononuclear cells of bone marrow aspirate)
• Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible
• Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception
• Male patient who reject the methods of avoiding pregnancy via methods such as abstinence, barrier method (condom etc).
• Patients with a diagnosis of prior malignancy (including hematologic malignancies such as acute leukemia, lymphoma, multiple myeloma, and myelodysplastic syndrome, etc) unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Young/MUD&FMD	AlloHCT for Young/MUD&FMD	Patients who are \<55 years old, and will receive alloHCT for Young/MUD\&FMD
Old/MSD	AlloHCT for Old/MSD	Patients who are \>=55 years old, and will receive alloHCT for Old/MSD
Young/MSD	AlloHCT for Young/MSD	Patients who are \<55 years old, and will receive alloHCT for Young/MSD
Old/MUD&FMD	AlloHCT for Old/MUD&FMD	Patients who are \>=55 years old, and will receive alloHCT for Old/MUD\&FMD

Primary Outcome Measures

Name	Time	Method
relapse-free survival (RFS) rate	2 years	time from achieving hematologic CR to hematologic relapse / time from the enrollment of this trial to hematologic relapse

Secondary Outcome Measures

Name	Time	Method
treatment-related mortality rate	5 years	after enrollment of this trial
cumulative incidence of acute graft-versus-host disease	5 years	after enrollment of this trial
cumulative incidence of chronic graft-versus-host disease	5 years	after enrollment of this trial
molecular relapse-free survival	2 years	after enrollment of this trial / after achieving molecular CR (for Ph-positive ALL)
relapse-free survival (RFS) rate	5 years	time from achieving hematologic CR to hematologic relapse / time from the enrollment of this trial to hematologic relapse
overall survival (OS) rate	5 years	time from the diagnosis of disease to death/ time from the enrollment of this trial to death
cumulative incidence of relapse	5 years	from achieving hematologic CR to hematologic relapse / time from the enrollment of this trial to hematologic relapse

Trial Locations

Locations (4)

Inje University Busan Paik Hospital; 🇰🇷 Busan, Korea, Republic of

Inje University Haeundae Paik Hospital; 🇰🇷 Busan, Korea, Republic of

Asan Medical Center, University of Ulsan College of Medicine; 🇰🇷 Seoul, Korea, Republic of

Ulsan University Hospital, University of Ulsan College of Medicine; 🇰🇷 Ulsan, Korea, Republic of