Acute Myelogenous Leukemia Clinical Trial
Official title:
Two-Step Remission Induction With Risk-Oriented Consolidation (High-Risk: Allogeneic Stem Cell Transplant; Standard-Risk: Multicycle High-Dose Cytarabine With Autologous Blood Stem Cell Support) for Adult Acute Myelogenous Leukemia
The study was set up to assess:
1. A two-step, increasing-intensity remission induction phase. A conventional chemotherapy
course (ICE, plus G-CSF) was followed, in unresponsive patients, by sequential
high-dose cytarabine (plus G-CSF), aiming to provide an early effective rescue to as
many refractory cases as possible.
2. A risk-oriented postremission consolidation phase. The objective was to adopt
allogeneic stem cell transplantation (alloSCT) in high-risk (HR) cases, while
standard-risk (SR) ones were consolidated with a multicycle high-dose
cytarabine-containing program, which included the use of autologous stem cells plus
G-CSF to limit drug-related toxicity and intercycle treatment delays.
Adult AML is a difficult-to-treat illness because of both biological and therapeutic
reasons.
As to the first point, many patients are aged >50 years and/or present with significant
comorbidity and/or AML-related risk features (poor risk cytogenetics, prior myelodysplasia,
secondary AML).
As to the second point, standard-type remission induction therapy is ineffective in 20% or
more of the patients, whereas the application of the more effective postremission
consolidation options (alloSCT, high-dose cytarabine courses) is often flawed by high-grade
toxicity which can offset expected benefits, particularly in older age groups (>50-55
years), where therapy-related death rates are seen in 5%-10% of the cases (chemotherapy) or
more (transplants).
Against this background an explorative study was developed in which:
1. All patients aged 16-65 years were considered eligible (acute promyelocytic leukemia
excluded), including those with an antecedent diagnosis of myelodysplasia/hematological
disorder and/or secondary AML. Both age and disease subtype selection criteria are
broader than in most studies on adult AML, adhering more closely to the reported
epidemiology of the disease.
2. Remission induction was attempted with a two-step regimen, consisting of conventional
chemotherapy (ICE: idarubicin/cytarabine/etoposide +G-CSF) followed, only in the case
of failure to respond, by a sequential high dose-cytarabine cycle (cytarabine 3 g/m2/bd
on days 1,2,8,9; idarubicin on days 3 and 10; G-GSF; cytarabine dosing 2 g/m2 in
patients aged >55 years). It was hoped that this choice would optimize salvage rates
(hence overall response rates), by allowing more patients (and more fit, uncomplicated
ones) to reach the salvage phase, compared to a policy where salvage is usually given
after two failed induction courses.
3. Remission consolidation was risk-oriented, the risk being defined through a mixed
clinico-cytogenetic model. Thus all patients entering CR after one/two cycles were
stratified as HR or SR according to what is reported below. Once defined the risk
class, therapy consisted of an alloSCT for HR patients, and of 3 consecutive monthly
cytarabine-based cycles (2 g/m2/bd on days 1-5; idarubicin on days 1,2) in SR patients,
each cycle being followed by the reinfusion of a limited amount of autologous blood
stem cells (1-2x10e6/kg CD34+ cells) and G-CSF. Blood stem cells were collected
following an early consolidation cycle with intermediate-dose cytarabine plus G-CSF. HR
patients unable/unfit to proceed to alloSCT were offered instead the SR-type multicycle
cytarabine consolidation, whereas all patients unable to mobilize autologous stem cells
were treated with one/two intermediate-dose cytarabine course(s).
HR: high-risk cytogenetics or intermediate-risk/normal cytogenetics with FLT3 mutation
and/or any one or more additional clinical risk factor(s), i.e. total WBC >50x10e9/l, FAB
subtype M0, M6 or M7, prior myelodysplasia or secondary AML,hepatosplenomegaly, late CR
(cycle 2), or favorable cytogenetics with late CR (cycle 2).
SR: favorable cytogenetics (without associated high-risk abnormalities and in CR after cycle
1) or intermediate-risk/normal cytogenetics without FLT3 mutation and/or without any one
additional clinical risk factor(s), i.e. total WBC >50x10e9/l, FAB subtype M0, M6 or M7,
prior myelodysplasia or secondary AML,hepatosplenomegaly, late CR (cycle 2).
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT01200355 -
Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
|
Phase 4 | |
Active, not recruiting |
NCT03755414 -
Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation
|
Phase 1 | |
Recruiting |
NCT04904588 -
HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide
|
Phase 2 | |
Active, not recruiting |
NCT04188678 -
Resiliency in Older Adults Undergoing Bone Marrow Transplant
|
N/A | |
Completed |
NCT02543879 -
Study of a Novel BET Inhibitor FT-1101 in Patients With Relapsed or Refractory Hematologic Malignancies
|
Phase 1 | |
Completed |
NCT01681537 -
Lenalidomide Plus Chemotherapy for AML
|
Phase 1 | |
Completed |
NCT01385423 -
Haploidentical Donor Natural Killer Cell Infusion With IL-15 in Acute Myelogenous Leukemia (AML)
|
Phase 1 | |
Terminated |
NCT01193400 -
Clofarabine and Low-dose Cytarabine Followed by Consolidation Therapy in AML Patients Age Greater Than or Equal to 60 Years
|
Phase 2 | |
Completed |
NCT00995332 -
Disease Stabilization in AML by Treatment With ATRA, Valproic Acid and Low-dose Cytarabine
|
Phase 1/Phase 2 | |
Completed |
NCT00981240 -
Dose Escalation, Safety and Pharmacokinetic Study of SAR103168 in Patients Refractory/ Relapsed Acute Leukemias or High-risk Myelodysplastic Syndromes
|
Phase 1 | |
Completed |
NCT00975975 -
Basiliximab #2: In-Vivo Activated T-Cell Depletion to Prevent Graft-Versus_Host Disease (GVHD) After Nonmyeloablative Allotransplantation for the Treatment of Blood Cancer
|
Phase 2 | |
Completed |
NCT00726934 -
The Effectiveness of the Neutropenic Diet in Pediatric Oncology Patients
|
N/A | |
Completed |
NCT00378534 -
Methods to Enhance the Safety and Effectiveness of Stem Cell Transplants
|
Phase 2 | |
Completed |
NCT01031498 -
Palonosetron Versus Ondansetron for the Prevention of Nausea and Vomiting
|
Phase 2 | |
Completed |
NCT00789256 -
Low Dose Melphalan and Bortezomib for AML and High-Risk MDS
|
N/A | |
Completed |
NCT00098033 -
Investigation of Clofarabine in Acute Leukemias
|
Phase 2 | |
Completed |
NCT01020539 -
Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Leukemia
|
Phase 1 | |
Not yet recruiting |
NCT04709458 -
Safety and Early Efficacy Study of TBX-2400 in Patients With AML or Myelofibrosis
|
Phase 1 | |
Recruiting |
NCT04024241 -
Medium Dose of Cytarabine and Mitoxantrone
|
||
Terminated |
NCT02203773 -
Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)
|
Phase 1 |