Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Etoposide

Cytarabine

Daunorubicin

Etoposide phosphate

Asparaginase

Sorafenib

Gemtuzumab

Calicheamicins

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Protein Kinase Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Participants in this arm will receive the standard Aflac-AML Regimen with the following chemotherapy:

* Induction-1: patients on Induction-I will receive gemtuzumab + ADE therapy based on genotyping. Lasts a total of 28 days.
* Induction II - MA
* Intensification I - AE
* Intensification II - HD ARAC/LASP

Patients with low risk status who had low risk markers and were MRD positive at the end of Induction I and continue to be MRD positive after Induction II will come off protocol.

Participants in this arm will receive standard Aflac-AML Regimen with the following chemotherapy:

* Induction-1: patients will receive gemtuzumab in addition to ADE therapy based on genotyping. Induction I lasts a total of 28 days.
* Induction 1 for FLT3-ITD patients - ADE (10+3+5) with GO with Sorafenib
* Induction II - MA
* Induction II for FLT3-ITD patients - MA with Sorafenib
* Intensification I - AE
* Intensification I for FLT3-ITD patients - AE with sorafenib
* Intensification II - HD ARAC/LASP
* Intensification II for FLT3-ITD patients - HD ARAC/LASP with sorafenib
* Hematopoietic stem cell transplantation (HSCT)

If a patient is classified as High risk after Induction I, they may proceed to best allogenic donor SCT following Induction II. These patients may receive a third course of chemotherapy prior to HSCT. In cases where HSCT is not an option, patients can receive 4 cycles of chemotherapy. Only patients with FLT3-ITD mutation will receive sorafenib.

100 mg/m²/dose every 12 hours IV Days 1-10

25,000 International Units/m²/dose IM Days 2, 9

Erwinase

Administered as a single 3 mg/m2 dose of GO to be given between days 6-10 during Induction I for patients with CC genotype, in addition to ADE therapy.

Gemtuzumab ozogamicin

Transplantation of multipotent hematopoietic stem cells from bone marrow

Stem cell transplantation (SCT)

200 mg/m2/dose daily, rounded to accommodate tablet size. The maximum dose will be 400 mg. Days 7 through 34.

Himalee Sabnis, MD

The investigators propose to study an Aflac-AML chemotherapy backbone prospectively to validate its use in all pediatric AML and to further evaluate the cardiotoxicity with this approach for low risk AML.

Advances in risk stratification and therapy, have improved the event-free survival (EFS) and overall survival (OS) for pediatric acute myeloid leukemia (AML) to approximately 50% and 65% respectively, with current treatment strategies. Patients with good response to induction and/or those who lack high-risk cytogenetic and molecular features \[classified as low-risk AML (LR-AML)\] have even better outcomes with EFS and OS approaching 70% and 85% respectively; however, treatment-related toxicities remain a major concern. Anthracycline-based therapeutic regimens expose patients to the risk of anthracycline-induced cardiotoxicity. Therefore, strategies that reduce cardiac toxicities using tailored approaches while maintaining and/or improving outcomes are needed for all patients with AML. The Children's Oncology Group (COG) regimens AAML1031 and AAML0531 utilized an anthracycline-intensive backbone for LR-AML with cumulative anthracycline doxorubicin-equivalent doses of up to 492mg/m2. However, high-risk patients treated with chemotherapy alone received an intensified induction chemotherapy (using mitoxantrone-cytarabine) but with overall reduced doses of anthracycline-equivalent (342mg/m2). The investigators piloted an institutional practice to treat all LR-AML patients with four cycle regimen (Aflac-AML) with the goal of reducing cumulative anthracycline exposure, thereby reducing the risk of cardiotoxicity, while providing three high-dose cytarabine courses. In this pilot institutional experience with this approach, they were able to maintain excellent outcomes for this low-risk group with 3-year event-free survival (EFS) and OS of 70.0% ± 0.1% and 85.5% ± 0.08% respectively, from end of course 1. Recent evolution in cytogenetic classification has further delineated risk groups in AML. Gemtuzumab ozogamicin (GO), an antibody-drug conjugate was shown to reduce relapse risk in patients with CC genotype with de-novo AML on COG study AAML0531. The investigators propose to study an Aflac-AML chemotherapy backbone prospectively to validate its use in all pediatric AML and to further evaluate the cardiotoxicity with this approach for low risk AML.

AflacLL1901 (CHOA-AML)

CHOA-AML: A Pilot Study for Newly Diagnosed Pediatric Patients With Acute Myeloid Leukemia (AML)

Event-free survival defined as the time from on study to death, failure to achieve remission or relapse in newly diagnosed patients with pediatric acute myeloid leukemia in the Low risk stratification group and High risk stratification group

Time from study entry and from end of first course of therapy for newly diagnosed patients with pediatric acute myeloid leukemia

Number of patients that are in remission (MRD negative) after course 1 in participants receiving GO and those that did not receive GO.

Disease-free survival for patients who are MRD negative but lack high or low risk molecular and cytogenetic features, defined as time from end of first course of therapy to death or relapse

Number of patients that develop cardiac ejection fraction \<50% (CTCAE V5.0 grade 2 or greater dysfunction) either during therapy (early cardiotoxicity) or after completion of therapy (late cardiotoxicity)

Number of participants that developed infection and/or febrile neutropenia at the end of each treatment cycle.

Duration of hospital admission in patients that developed infection and febrile neutropenia at the end of each treatment cycle

Emory University

Assistant Professor

Participants in this group received AraC/Daunorubicin/Etoposide (10+3+5) +/- GO based on CC genotype\^ Patients were classified into risk groups following Induction I

* \^If has FLT3-ITD mutation, Sorafenib is added

Induction I

Participants in this group received Mitoxantrone/AraC

Low Risk - Induction II

Participants in this group received Mitoxantrone/AraC\^

* \^If has FLT3-ITD mutation, Sorafenib is added

High Risk - Induction II

Participants in this group received AraC/Etoposide

Low Risk - Intensification I

Participants in this group received HD AraC/Asparaginase

Low Risk - Intensification II

Patients were classified as low risk following Induction I. All were MRD negative without low or high risk genetic and prognostic factors.

* Induction I: AraC/Daunorubicin/Etoposide (10+3+5) +/- GO based on CC genotype
* Induction II: Mitoxantrone/AraC
* Intensification I: AraC/Etoposide
* Intensification II: HD AraC/Asparaginase

Aflac-AML Low Risk Patients

Patients were classified as high risk following Induction I. All were MRD negative with high risk genetic and prognostic factors.

Induction I: AraC/Daunorubicin/Etoposide (10+3+5) +/- GO based on CC genotype\^ Induction II: Mitoxantrone/AraC\^ Intensification:\* AraC/Etoposide\^ OR HD AraC/Asparaginase\^ Allogenic HSCT

* \^If has FLT3-ITD mutation, Sorafenib is added
* \* Depending on timing patients may proceed to HSCT following Induction II or receive Intensification. If HSCT is not an option, patients can receive 4 cycles of chemotherapy

Aflac-AML High Risk Patients

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Himalee Sabnis

Event-free Survival (EFS) in Low Risk Patients and High Risk Patients

Overall Survival (OS)

Patients with CC genotype received Induction 1 AraC/Daunorubicin/Etoposide (10+3+5) with Gemtuzumab ozogamicin (GO)

Induction I With GO

Patients without CC genotype received Induction 1 AraC/Daunorubicin/Etoposide (10+3+5)

Induction I Without GO

Minimal Residual Disease (MRD) Negative Status

Patients who are MRD negative but lack high or low risk molecular and cytogenetic features, defined as time from end of first course of therapy to death or relapse.

Patients Who Are MRD Negative

All patients were MRD negative at the end of Induction I. No patients were assigned low risk due to low risk molecular and cytogenetic features. All high risk patients had high risk molecular and cytogenetic features.

Disease-free Survival (DFS) for Patients Who Are MRD Negative

Early cardiotoxicity

Late cardiotoxicity

The definition of late cardiotoxicity is after completion of therapy. All 3 of the high risk patients came off protocol early and did not complete therapy. For the low risk patients, 2 did not complete therapy. Among the 3 that did complete therapy, 1 patient has been lost to follow-up since completion of therapy with no cardiac data available.

Cardiotoxicity in Patients With de Novo AML That Receive the Four-cycle Aflac-AML Regimen With the Inclusion of Dexrazoxane

Cycle 1 - Induction 1

Cycle 2 - Induction 2

Cycle 3 - Induction 3

Cycle 4 - Induction 4

All 3 of the high risk patients came off protocol early and did not complete therapy. For the low risk patients, 2 did not complete therapy. Among the 3 that did complete therapy, 1 patient has been lost to follow-up since completion of therapy with no cardiac data available.

Proportion of Patients Who Develop Infection and/or Febrile Neutropenia During Each Treatment Course

Duration of Hospital Admission in Patients That Developed Infection and Febrile Neutropenia at the End of Each Treatment Cycle

Overall Study

Immune System Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hypersensitivity

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Cardiotonic Agents

Micronutrients

Hematinics

Vitamins

Dexamethasone

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Doxorubicin

Liposomal doxorubicin

Methotrexate

Vincristine

Dexamethasone acetate

BB 1101

Dexrazoxane

Razoxane

Dexamethasone 21-phosphate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Tubulin Modulators

Antimitotic Agents

Protective Agents

Folinic Acid

Folate

Vitamin B9

All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.

The dose of Erwinase will be assigned at study entry. The first dose of Erwinase wil be given between Days 3-5 and will continue on a M-W-F schedule for a total of 10 doses.

Erwinase will be administered as a 2-hour intravenous infusion.

1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22

10 mg/m2/day divided BID. Give by mouth days 1-14.

Given Intrathecally at the dose defined by age on day 1. 30 mg for age 1-1.99 50 mg for age 2-2.99 70 mg for age 3 and older

Given Intrathecally to all patients who are CNS 1 or 2 at study entry. Dose defined by age. Given on day 15 8mg for age 1-1.99 10 mg for age 2-2.99 12 mg for age 3-8.99 15 mg for age 9 and older

Methotrexate, Cytarabine and Hydrocortisone given Intrathecally on day 8, 15 and 22 for patients who are CNS 3 at study entry. Doses determined by age.

Triple Intrathecal Therapy

Due to the limited availability of Dexrazoxane (Zinecard®), treatment will be at the discretion of the treating physician. Dose should be 600 mg/m2 as a IV push immediately prior to anthracycline dose (the elapsed time from the beginning of the dexrazoxane dose to the end of the anthracycline infusion should be 30 minutes or less).

Heather Grossman, MD

Paul Gaynon, MD

This is a phase I study using the Erwinia form of asparaginase in place of the E. coli form using a standard re-induction regimen (Vincristine, Dexamethasone, Doxorubicin) for patients with relapsed ALL who have developed an allergy to the E. coli formulation. This study will administer the drug intravenously instead of the usual intramuscular route. The dose of Erwinia will be escalated in the absence of dose limiting toxicity. Patients must have first or second relapse ALL with a history of prior systemic reaction to E. coli asparaginase.

Significance

1. Substitution of Erwinase after E.coli asparaginase allergy has been standard practice despite the paucity of evidence regarding its efficacy and uncertainty about dose. Definition of an appropriate dose and schedule of Erwinase that provides reliable asparagine depletion may be useful for patients with clinical allergy to E. coli asparaginase, both in first remission or after relapse.
2. Patients in relapse may have a different level of asparagine synthesis than patients maintaining remission and require different asparaginase dosing.5
3. Intravenous administration provides more rapid and predictable asparagine depletion with less discomfort and danger of bleeding for often thrombocytopenic patients than intramuscular administration.
4. Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with first marrow relapse.
5. Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with second marrow relapse, if the duration of CR2 \> 18 months year.

Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (IND 104224)

Intravenous Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia and Allergy to E. Coli Asparaginase (IND 104224)

The MTD in each stratum will be the highest dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy.

Disease response evaluated by examination and labs. MRD evaluated from marrow samples.

Activity levels assessed from PK sampling

Therapeutic Advances in Childhood Leukemia Consortium

The definition of AE and SAE do not differ from the clinicaltrials.gov definitions.

All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.

Erwinase: The dose of Erwinase will be assigned at study entry. The first dose of Erwinase wil be given between Days 3-5 and will continue on a M-W-F schedule for a total of 10 doses.

Erwinase will be administered as a 2-hour intravenous infusion.

Vincristine: 1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22

Dexamethasone: 10 mg/m2/day divided BID. Give by mouth days 1-14.

Doxorubicin: 60 mg/m2/day IV over 15 minutes on day 1

Cytarabine: Given Intrathecally at the dose defined by age on day 1. 30 mg for age 1-1.99 50 mg for age 2-2.99 70 mg for age 3

Single Arm

Age, Categorical

The study closed early due to lack of accrual and insufficient funding. Only one patient was enrolled. This patient completed the protocol therapy.

Peggy Romano, BA, CCRP

Occurrence of a Dose-Limiting Toxicity

Study closed early due to lack of accrual, and insufficient data were collected for performing this analysis.

Response Rate and Minimum Residual Disease

Study closed early due to lack of accrual and insufficient data were collected to perform this analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
AflacLL1901 (CHOA-AML)	NCT04326439	Acute Myeloid L... AML, Childhood	Cytarabine Daunorubicin Erwinase Etoposide Gemtuzumab ozog... Stem cell trans... Sorafenib	- 21 Years	Emory University
Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (IND 104224)	NCT00928200	Relapsed Acute ... Allergy to PEG ... Allergy to Nati...	Erwinase Vincristine Dexamethasone Doxorubicin Cytarabine Methotrexate Triple Intrathe... Dexrazoxane	1 Year - 21 Years	Therapeutic Advances in Childhood Leukemia Consortium
AflacLL1901 (CHOA-AML)	NCT04326439	Acute Myeloid L... AML, Childhood	Cytarabine Daunorubicin Erwinase Etoposide Gemtuzumab ozog... Stem cell trans... Sorafenib	- 21 Years	Emory University
Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017	NCT03643276	Acute Lymphobla...	Blinatumomab Bortezomib Cyclophosphamid... Cytarabine Daunorubicin Myocet Dexamethasone Doxorubicin Etoposide Fludarabine Pho... Ifosfamide 6-Mercaptopurin... Methotrexate Pegaspargase Prednisolone Tioguanin Vincristine Vindesine Erwinase	- 17 Years	University Hospital Schleswig-Holstein
Erwinase Study in Patients With Acute Lymphoblastic Leukemia	NCT00506597	Leukemia	Erwinase	-	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for erwinase

Every month we try and update this database with for erwinase 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 erwinase

Every month we try and update this database with for erwinase 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 erwinase 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.