Clinical trial NCT02428517: Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia (2015)
Official title: A Prospective Study Evaluating the Efficacy of the Allogeneic Hematopoietic Cell Transplantation With Antithymocyte Globulin (ATG)-Based Conditioning of Adult Acute Lymphoblastic Leukemia in First / Second Complete Hematologic Remission
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Keywords: acute lymphoblastic leukemia
allogeneic hematopoietic stem cell transplantation
alternative hematopoietic stem cell donor
busulfan
antithymocyte globulin
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2015-04-28
Enrollment: 20
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who are diagnosed as acute lymphoblastic leukemia, who achieve hematologic complete remission for the first time or for the second time after chemotherapy, and who wil receive allogeneic hematopoietic cell transplantation

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.

Eligibility criteria: 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.

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)

Primary outcomes:
measure: relapse-free survival (RFS) rate
timeFrame: 2 years
Secondary outcomes:
measure: relapse-free survival (RFS) rate
timeFrame: 5 years
measure: overall survival (OS) rate
timeFrame: 2 years
measure: overall survival (OS) rate
timeFrame: 5 years
measure: cumulative incidence of relapse
timeFrame: 2 years
measure: cumulative incidence of relapse
timeFrame: 5 years
measure: treatment-related mortality rate
timeFrame: 100 days
measure: treatment-related mortality rate
timeFrame: 1 year
measure: treatment-related mortality rate
timeFrame: 2 years
measure: treatment-related mortality rate
timeFrame: 5 years
measure: cumulative incidence of acute graft-versus-host disease
timeFrame: 100 days
measure: cumulative incidence of acute graft-versus-host disease
timeFrame: 1 year
measure: cumulative incidence of acute graft-versus-host disease
timeFrame: 2 years
measure: cumulative incidence of acute graft-versus-host disease
timeFrame: 5 years
measure: cumulative incidence of chronic graft-versus-host disease
timeFrame: 100 days
measure: cumulative incidence of chronic graft-versus-host disease
timeFrame: 1 year
measure: cumulative incidence of chronic graft-versus-host disease
timeFrame: 2 years
measure: cumulative incidence of chronic graft-versus-host disease
timeFrame: 5 years
measure: molecular relapse-free survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, University of Ulsan College of Medicine
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital, University of Ulsan College of Medicine
Study officials:
affiliation: Asan Medical Center
name: Dae-Young Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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