Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Pathologic Complete Response

Neoplasms by Histologic Type

Hematologic Diseases

Disease Progression

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Subject on this arm will be treated with HiDAC prospectively.

Subjects on this arm will be historical controls who have previously received treatment with HiDAC.

Subjects on this arm will prospectively receive consolidation therapy with cytarabine. Subjects will be treated with 1000 mg/m2 cytarabine intravenously every 12 hours on Days 1-3 of each consolidation cycle. Subjects will receive up to four consolidation cycles.

Subjects on this arm will have received consolidation therapy with cytarabine between 2/1/2017 and 2/1/2019. Subjects will have received 1000 mg/m2 cytarabine intravenously every 12 hours on days 1, 3, and 5 of each consolidation cycle and will have received up to 4 consolidation cycles.

Jack Hsu, MD

This phase 2, open label, non-randomized study will evaluate the safety of administering high dose cytarabine (HiDAC) consolidation therapy on days 1-3 of each cycle, as compared to standard administration on days 1, 3, and 5 of each cycle, in patients 61 years and older with de novo acute myeloid leukemia (AML).

Accelerated Dose Schedule of Cytarabine Consolidation Therapy for Older Patients With Acute Myeloid Leukemia (AML) in Complete Remission

Accelerated Dose Schedule of Cytarabine Consolidation Therapy for Patients With Acute Myeloid Leukemia (AML) in Complete Remission

Determine the duration of neutropenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135.

Determine the duration of thrombocytopenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135.

Compare the incidence of documented infections (bloodstream infection, pneumonia, invasive fungal infection, Clostridium difficile infection, typhlitis, and febrile neutropenia) in patients receiving HiDAC 123 and HiDAC 135.

Compare the number of red blood cell and platelet transfusions per cycle in patients receiving HiDAC 123 and HiDAC 135.

Compare the incidence of readmission and the length of readmission stay in patients receiving HiDAC 123 and HiDAC 135.

Compare the differences in non-hematologic toxicities in patients receiving HiDAC 123 and HiDAC 135.

Compare the time to next treatment (next chemotherapy cycle, transplant, etc.) in patients receiving HiDAC 123 and HiDAC 135.

University of Florida

Wounds and Injuries

Hyperthermia

Neutropenia

Fever

Febrile Neutropenia

Agranulocytosis

Leukopenia

Cytopenia

Leukocyte Disorders

Granulocytopenia

Temperature Monitoring Device Group - The interventional group, who will be given the temperature monitoring device and will be monitored remotely.

Historic cohort group will be enrolled from medical record

The patient will be set up with a remote monitoring device for temperature recording and the temperature will monitored remotely

Remote monitoring of temperature

Locke J. Bryan, MD

Febrile neutropenic patients are at high risk for developing sepsis and other infections which often necessitates acute admission to the Intensive Care Unit (ICU) and are associated with high mortality. Neutropenic fever is a medical emergency and early detection of fever allows for prompt infectious work up. In this study, the investigators will collect pilot data from outpatients utilizing a remote outpatient continuous temperature monitoring device to compare the incidence of ICU admission and severe sepsis to historical data for prior patients who did not receive at home monitoring device.

Interventional group will be compared with historic group of patients

Remote Outpatient Temperature Monitoring for Early Detection of Febrile Neutropenia After Chemotherapy

This study result will be used for service improvement of patient of the Augusta University Medical Center

The interventional group will have changed in the number of ICU admission.

The interventional group will have changed rate of sepsis incidence.

University of Georgia

Augusta University

Analgesics

Mitoxantrone

Fludarabine

Fludarabine phosphate

Daunorubicin

Idarubicin

Cladribine

Lenograstim

Adjuvants, Immunologic

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Induction I:

* DNR 90 mg/m2 D 1-3 in 30-60 min i.v. infusion
* Ara-C 100 mg/m2 D 1-7 in 24 h i.v. infusion

Induction I:

* DNR 60 mg/m2 D 1-3 in 30-60 min i.v. infusion
* cladribine 5 mg/m2 D 1-5 in 2 h i.v. infusion prior to Ara-C
* Ara-C 200 mg/m2 D 1-7 in 22 h i.v. infusion.

Cladribine 5mg/m2 in 2 h i.v. infusion on days (1-5) Ara-C 2 g/m2 in 4 h i.v. infusion, 2 h after cladribine infusion on days (1-5) Mitoxantrone 10 mg/m2 i.v. 1xd on days (1-3) G-CSF 30MU s.c. 1xd from day 0 to 5 of the treatment (6 doses).

Fludarabine 30 mg/m2 in 30-min i.v. infusion on days (1-5) Ara-C 2 g/m2 in 4 h i.v. infusion, 2 h after fludarabine infusion on days (1-5). Idarubicin 8 mg/m2 i.v. 1xd on days (1-3) G-CSF 30MU s.c. 1xd from day 0 to 5 of the treatment (6 doses).

After confirming the diagnosis, assuming the inclusion criteria and exclusion criteria are respected, the patients are randomized to one of two standard induction treatment protocols (A arm: DA-90 vs B arm: DAC). After completing induction I, an early bone marrow assessment is performed on day 14 from the beginning of the treatment (+ day 7 after finishing chemotherapy) using the cytological method and MRD is assessed by the immunophenotyping method. Therapeutic decision is taken on the basis of the cytological assessment. Patients, in whom the percentage of blasts in the bone marrow on day 14 is \> 10%, receive early induction II from day 16. An Immunophenotype test is a complementary examination.

A arm (DA-90)

B arm (DAC)

Patients who do not achieve CR after two courses of induction therapy or patients with relapsed leukemia are eligible for emergency treatment ("salvage") according to the CLAG- M or FLAG-IDA protocol.

A arm (CLAG-M)

B arm (FLAG-IDA)

Agnieszka Wierzbowska, Prof.

Gail Roboz, Prof.

Jarosław Piszcz, Dr

Andrzej Pluta, Dr

Maria Bieniaszewska, Dr

Marzena Wątek, Dr

Małgorzata Raźny, Dr

Jadwiga Hołojda

Marek Hus, Prof.

MAciej Kaźmierczak, Dr

Sebastian Giebel, Prof.

The study will include newly-diagnosed AML patients, not suffering acute promyelocytic leukemia; aged 18-60 years, who are eligible for standard induction chemotherapy. The patients will be randomized to one standard induction regimen (DAC or DA-90). At day seven after completion of induction, a bone marrow aspiration with MRD will be performed for an early evaluation of response to treatment. Patients without bone marrow blast reduction below 10% at day seven after induction will be given a second early induction course. Patients who do not achieve CR after two induction courses will be randomized to one of the standard salvage regimens (FLAG-IDA or CLAG-M). Postremission treatment intensity will be adjusted to risk group based on cytogenetic and molecular risk factors at diagnosis and AML biology (secondary AML, therapy related AML). Patients with a low risk of relapse will be allocated to consolidation, with three courses of high doses of Ara-C (HiDAC), or two courses of HiDAC with subsequent autologous stem cell transplantation. Intermediate- or high-risk patients will be referred for allogeneic stem cell transplantation, if they have a matched donor. Until transplantation, consolidation with HiDAC will be continued.

The successful treatment of acute myeloid leukemia (AML) depends on the ability to achieve complete remission (CR) and to prevent relapse. Both may be affected by the efficacy of induction chemotherapy. The gold standard for treatment since 1982 has been DA, a regimen of three days of daunorubicin (DNR) and seven days of cytarabine (Ara-C) which results in complete remission in 50 to 75% of patients; this is typically administered intravenously, with daunorubicin administered at a dose of 45 mg per square meter of body-surface area daily for three days, and cytarabine given at a dose of 100 mg per square meter daily for seven days. Neither substituting DNR with another anthracycline nor the addition of thioguanine or etoposide has been demonstrated to improve outcome. Recently it has been proved that high-dose daunorubicin (90 mg/m2) in induction (DA-90) resulted in a higher rate of complete remission (70.6% vs. 57.3%, P\<0.001) and improved overall survival (median, 23.7 vs. 15.7 months; P = 0.003) without any increase in serious adverse events, compared with the standard dose of the drug.

An alternative method to intensify induction treatment is by the addition of the purine analog cladribine. Cladribine was demonstrated to increase cellular uptake of Ara-C and accumulation of Ara-CTP in leukemic blasts by 50% to 65% and to have direct antileukemic activity based on incorporation of metabolites into the DNA of proliferating cells. In two randomized trials by the Polish Adult Leukemia Group (PALG), the investigators demonstrated that the combination of cladribine with DNR (60 mg/m2) and Ara-C (DAC) resulted in a significantly increased CR rate after a single induction course compared with the standard two-drug induction (DA-60). The DAC arm was found to have a survival advantage over the DA-60 arm for patients aged 50 years or older (P =. 005), those with an initial leukocyte count above 50G /L (P \< .03), and those with an unfavorable karyotype (P \< .03). Both induction protocols have the same level of recommendation by the National Cancer Comprehensive Network (NCCN) for routine use (level I), and are commonly used for the treatment of newly diagnosed AML in Poland.

As no randomized comparison of these two standard protocols has yet been performed, the aim of the proposed study is to compare the efficacy of these two standard induction protocols in terms of achievement of CR, early leukemia elimination (at day seven, post induction) and quality of remission measured by minimal residual disease level. Additionally, overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) will be analyzed. It is also intended to compare the hematological and non-hematological toxicity of both regimens.

However, in younger adults with AML treated with standard induction chemotherapy, 20-35% do not achieve CR and 50-70% with CR may be expected to relapse within three years. Patients with primary refractory disease and with relapses following CR1 have a significantly poorer outcome. The optimum strategy at the time of relapse or for patients with refractory disease remains uncertain. Allogeneic transplantation can be curative for the minority of patients who achieve second CR (2CR) and for whom a suitable donor is available. For the majority of patients, additional chemotherapy is given in the hope of achieving remission. Most salvage therapies utilize high or intermediate doses of arabinoside cytosine (Ara-C) in combination with other agents to overcome resistance in leukemic cells. Previous studies have shown that a combination of the purine analog fludarabine (FA) and cytosine arabinoside (Ara-C) increases the accumulation of Ara-C-5' triphosphate (Ara-CTP) responsible for the cytotoxic effect in leukemic blasts. This combination of FA plus Ara-C was initially explored in refractory and relapsed AML patients with satisfactory results. It is also likely that these results can be improved by the addition of granulocyte-colony stimulating factor (G-CSF). Such a combination of FA, Ara-C, idarubicin and G-CSF (the FLAG-IDA regimen) has been used in the treatment of refractory and relapsed AML and poor prognosis myelodysplastic syndromes (MDS), with CR rates of between 30-80% being reported. Recent studies have shown that another purine analog, cladribine (2-CdA), is also able to enhance Ara-CTP accumulation in leukemic blasts and that the combination of 2-Cda with Ara-C exhibited synergistic effect on inhibition of myeloid leukemic cell proliferation, induction of apoptosis, and on disruption of mitochondrial membrane potential.

Two previous PALG studies have confirmed that the CLAG-M regimen (a combination of cladribine, Ara-C, G-CSF and mitoxantrone) has high efficacy and low toxicity in refractory/relapsed AML patients. This salvage regimen was particularly effective in a very poor-risk subgroup with primary refractoriness, early relapse or relapse after stem cell transplantation. Both salvage protocols, CLAG-M and FLAG-Ida, are wildly used in the treatment of relapsed/refractory AML and both have the highest level of NCCN recommendation. However, these two standard salvage protocols have yet to be examined as part of any randomized study. Therefore, the aim of this study is to compare the efficacy of these two standard reinduction protocols (CLAG-M vs FLAG-IDA) in terms of achievement of CR, and quality of remission measured by minimal residual disease level. Additionally, the overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) will be analyzed. The study will also compare the hematological and non-hematological toxicity of both regimens.

The study will include newly-diagnosed AML patients, not suffering acute promyelocytic leukemia; aged 18-60 years, who are eligible for standard induction chemotherapy. The patients will be randomized to one standard induction regimen (DAC or DA-90). At day seven after completion of induction, a bone marrow aspiration with MRD will be performed for an early evaluation of response to treatment. Patients without bone marrow blast reduction below 10% at day seven after induction will be given a second early induction course. Patients who do not achieve CR after two induction courses will be randomized to one of the standard salvage regimens (FLAG-IDA or CLAG-M). Postremission treatment intensity will be adjusted to risk group based on cytogenetic and molecular risk factors at diagnosis and AML biology (secondary AML, therapy related AML). Patients with a low risk of relapse will be allocated to consolidation, with three courses of high doses of Ara-C (HiDAC), or two courses of HiDAC with subsequent autologous stem cell transplantation. Intermediate- or high-risk patients will be referred for allogeneic stem cell transplantation, if they have a matched donor. Until transplantation, consolidation with HiDAC will be continued.

The primary end point of the study is CR rate after one and two induction courses. The secondary end-points are the quality of CR (MRD), OS, DFS, PFS, CR rate after salvage regimen.

It is planned to include 582 patients with newly-diagnosed AML. This will allow a 10% difference in CR rate between DAC and DA-90 induction regimens to be confirmed with a power of 80% and level of significance 0.05.

The study includes neither any experimental drug nor procedures that are not of the standard of treatment for AML.

Comparison of the efficacy of two standard induction treatment protocols (DA-90 and DAC) in patients with newly-diagnosed AML (with the exception of acute promyelocytic leukemia). Comparison of the efficacy of two standard reinduction treatment protocols (CLAG-M and FLAG-IDA) in patients with refractory and relapsed AML.

A PALG Prospective Multicenter Clinical Trial to Compare the Efficacy of Two Standard Induction Therapies (DA-90 vs DAC) and Two Standard Salvage Regimens (FLAG-IDA vs CLAG-M) in AML Patients ≤ 60 Years Old

Comparison of total remission rates after 1 induction course of DA-90 and DAC.

Comparison of total remission rates after II induction course of DA-90 and DAC.

Comparison of total remission rates after I reinduction course of CLAG-M and FLAG-IDA

Comparison of total remission rates after II reinduction course of CLAG-M and FLAG-IDA

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Accelerated Dose Schedule of Cytarabine Consolidation Therapy for Older Patients With Acute Myeloid Leukemia (AML) in Complete Remission	NCT04914676	Acute Myeloid L...	Cytarabine Cytarabine	61 Years - 99 Years	University of Florida
Remote Outpatient Temperature Monitoring for Early Detection of Febrile Neutropenia After Chemotherapy	NCT04081753	Acute Myeloid L...	Remote monitori...	18 Years - 80 Years	Augusta University
A PALG Prospective Multicenter Clinical Trial to Compare the Efficacy of Two Standard Induction Therapies (DA-90 vs DAC) and Two Standard Salvage Regimens (FLAG-IDA vs CLAG-M) in AML Patients ≤ 60 Years Old	NCT03257241	Acute Myeloid L...	A arm (DA-90) B arm (DAC) A arm (CLAG-M) B arm (FLAG-IDA...	18 Years - 60 Years	Polish Adult Leukemia Group

Spots Global Cancer Trial Database for hidac

Every month we try and update this database with for hidac cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hidac

Every month we try and update this database with for hidac cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hidac cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.