Acute Myeloid Leukemia Clinical Trial
Official title:
Phase II Study of Early Allogeneic Blood Stem Cell Transplantation During Induction-chemotherapy Induced Aplasia in High-risk Acute Myeloid Leukemia
Karyotype is a major prognostic risk factor in patients with acute myeloid leukemia (AML)
translating into unfavourable outcome in case of poor-risk cytogenetic aberrations. Several
studies have shown that allogeneic hematopoietic stem cell transplantation (HSCT) after
myeloablative conditioning rather than autologous HSCT or consolidation chemotherapy result
in long-term disease control in this group of patients when achieving a first complete
remission. Nevertheless, the complete remission rate achievable is significantly lower than
in patients with a more favourable risk profile. In fact, only the minority of AML patients
with poor-risk cytogenetics, although having a suitable donor, proceed to HSCT due to
refractory disease or infectious complications during induction chemotherapy (IC). Further,
new data show that the course of therapy can be estimated as early as two weeks after the
initiation of the first course of IC with patients presenting with more than 10 % marrow
blasts doing significantly worse than those with a better clearance of blasts. As a result,
the chance to obtain a durable remission is considerably low and most patients with bad-risk
cytogenetics or failure to achieve blast clearance do not proceed to an allogeneic approach.
Together these data indicate that early treatment intensification is warranted in order to
provide the potential curative benefit of allogeneic HSCT to the majority of high-risk AML
patients.
We have shown that reduced-intensity conditioning (RIC) followed by allogeneic PBSC applied
during aplasia after the first cycle of IC in newly-diagnosed high-risk AML patients is
feasible and can result in a sustained disease control. These data prompted us to further
evaluate in a prospective trial an early "up-front HSCT" in patients with newly-diagnosed
high-risk AML defined by karyotype and insufficient blast clearance after the first cycle of
IC.
The goal was to provide an allogeneic HSCT as early as possible after diagnosis in AML
patients.
Only patients with newly-diagnosed AML are eligible for this prospective study. An immediate
donor-search, either within the family or in volunteer donor registries, will be performed
at diagnosis irrespective of the expected risk profile. All patients will receiv at least
one cycle of IC. Inclusion criteria for early allogeneic transplantation are either poor
risk cytogenetics and/or bad response to the first cycle of IC defined by more than 10%
marrow blasts on day 15. If a patient meets one of those criteria they could enter the early
allogeneic HSCT trial after providing informed consent. DNA-based HLA-typing of donor and
recipient will be performed using high resolution (4 digits) for HLA - A, B, DRB1 and DQB1
and intermediate resolution (2 digits) for HLA- C.
During IC-induced aplasia after the 1st or 2nd cycle a fludarabine-based reduced intensity
conditioning therapy will be started if a donor is available. All patients receive
fludarabine 30 mg/m2 i.v. daily for five days (day- 6 to -2) and melphalan 150 mg/m² on
day-2. Antithymocyte globulin (ATG Fresenius 10 mg/kg/day day -5 to -2, total dose 40 mg/kg,
Fresenius, Bad Homburg, Germany) will be applied after transplantation from unrelated or HLA
mismatched family donors. PBSC grafts will be preferred. As immunosuppression cyclosporin A
(CsA) is either administered intravenously at a dose of 3 mg/kg/day or given at an
bioequivalent amount of the oral formulation in two divided doses starting on the day before
blood stem cell infusion (day -1). The dose of CsA is adjusted to maintain blood levels
between 150 and 250 ng/ml. Starting on day 50, oral CsA administration will be tapered by 5%
weekly if GVHD was inactive. Acute and chronic GvHD will be treated with prednisone, CsA or
tacrolimus.
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05400122 -
Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer
|
Phase 1 | |
Recruiting |
NCT04460235 -
Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma
|
Phase 4 | |
Completed |
NCT03678493 -
A Study of FMT in Patients With AML Allo HSCT in Recipients
|
Phase 2 | |
Completed |
NCT04022785 -
PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
|
Phase 1 | |
Recruiting |
NCT05424562 -
A Study to Assess Change in Disease State in Adult Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy Receiving Oral Venetoclax Tablets in Canada
|
||
Terminated |
NCT03224819 -
Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML)
|
Early Phase 1 | |
Completed |
NCT03197714 -
Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia
|
Phase 1 | |
Active, not recruiting |
NCT04070768 -
Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113
|
Phase 1 | |
Active, not recruiting |
NCT03844048 -
An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
|
Phase 3 | |
Active, not recruiting |
NCT04107727 -
Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML)
|
Phase 2 | |
Recruiting |
NCT04385290 -
Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)
|
Phase 1/Phase 2 | |
Recruiting |
NCT04920500 -
Bioequivalence of Daunorubicin Cytarabine Liposomes in Naive AML Patients
|
N/A | |
Recruiting |
NCT03897127 -
Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics
|
Phase 3 | |
Active, not recruiting |
NCT04021368 -
RVU120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome
|
Phase 1 | |
Recruiting |
NCT03665480 -
The Effect of G-CSF on MRD After Induction Therapy in Newly Diagnosed AML
|
Phase 2/Phase 3 | |
Completed |
NCT02485535 -
Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant
|
Phase 1 | |
Enrolling by invitation |
NCT04093570 -
A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers
|
Phase 2 | |
Recruiting |
NCT04069208 -
IA14 Induction in Young Acute Myeloid Leukemia
|
Phase 2 | |
Recruiting |
NCT05744739 -
Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)
|
Phase 1 | |
Recruiting |
NCT04969601 -
Anti-Covid-19 Vaccine in Children With Acute Leukemia and Their Siblings
|
Phase 1/Phase 2 |