RECRUITING

A Pilot Study to Evaluate the Feasibility of Post-Hematopoietic Stem Cell Transplant Prophylaxis with Decitabine Combined with Filgrastim for Children and Young Adults with AML, MDS and Related Myeloid Malignancies

Conditions

Acute Myeloid Leukemia Myelodysplastic Syndromes Myeloid Malignancies MDS Inherited Bone Marrow Failure Syndrome Myeloid Neoplasm Aml

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to examine if it is feasible to administer decitabine and filgrastim after allogenic hematopoietic stem cell transplant (HCT) in children and young adults with myelodysplastic syndrome, acute myeloid leukemia and related myeloid disorders, and if the treatment is effective in preventing relapse after HCT. The names of the study drugs involved in this study are: * Decitabine (a nucleoside metabolic inhibitor) * Filgrastim (a recombinant granulocyte colony-stimulating factor (G-CSF)

Official Title

A Pilot Study to Evaluate the Feasibility of Post-Hematopoietic Stem Cell Transplant Prophylaxis with Decitabine Combined with Filgrastim for Children and Young Adults with AML, MDS and Related Myeloid Malignancies

Quick Facts

Study Start:2023-04-19

Study Completion:2029-09-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05796570

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year to 39 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Disease Criteria: Participants must have a histologically confirmed diagnosis of one of the following hematologic malignancies for eligibility, as defined by the criteria below: * AML (relapsed, de-novo or secondary) based on WHO classification * MDS (relapsed, de-novo or secondary) based on WHO classification * Treatment myeloid neoplasm (tMDS/AML; relapsed disease included) * Note: MDS, AML, MDS/AML, or tMDS/AML as defined above may be idiopathic/de novo or derived from a germline predisposition to myeloid malignancy. For patients with an underlying germline disorder, those conditions that are not associated with increased risk for toxicity to treatment, including patients with known germline ANKRD26, DDX41, ELANE and other congenital neutropenia disorders, ETV6, GATA-2, Li-Fraumeni, RUNX1, SAMD9/SAMD9L, or Shwachman-Diamond Syndrome, will be analyzed within the general treatment cohort (Cohort A, see Table 1) along with patients with idiopathic disease (Cohort B, see Table 2). * Dyskeratosis Congenita or associated telomeropathies as defined by telomere length \<1st percentile on 3 out of 4 lymphocyte subsets and/or corresponding pathogenic genetic mutation. * Fanconi Anemia as defined by positive chromosomal breakage test to DEB/MMC and/or corresponding pathogenic genetic mutation. * Nijmegen Breakage Syndrome as defined by positive chromosomal breakage test to DEB/MMC and/or corresponding pathogenic genetic mutation * ERCC6L2 by genomic testing. * germline mutations in ANKRD26 * germline mutations in DDX41 * ELANE and other Congenital Neutropenia Disorders * germline mutations in ETV6 * germline mutations in GATA-2 * Li-Fraumeni * germline mutations in RUNX1 * SAMD9/SAMD9L * Shwachman-Diamond Syndrome * Familial MDS with thrombocytopenia * Diamond-Blackfan Anemia * iBMF with Increased Risk for Treatment Related Toxicities: * Fanconi Anemia * Dyskeratosis Congenita and associated Telomere Disorders * Nijmegen Breakage Syndrome * ERCC6L2 * Patients must be receiving an allogeneic hematopoietic stem cell transplant. All donor types and graft sources are permitted. All conditioning regimens are permitted. All GVHD prophylaxis regimens are permitted. * Timing of Enrollment: Registration can occur from day - 30 to day - 10 prior to stem cell infusion. * Disease Status: Study enrollment will occur pre HCT. Any disease status is acceptable at the time of enrollment; however, patients must be in a MRD negative remission (as defined by multidimensional flow cytometry (MDF) post HCT prior to protocol treatment start). Post HCT/ pretreatment disease status will be performed by Hematologics. * No limitations on prior therapy. * Age ≥1 year and ≤ 39 year of age. * ECOG performance status ≤2 (Lansky, Karnofsky ≥60%). * Participants must have adequate organ function to be eligible for allogenic HCT as per institutional standard. * Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Anti- retroviral therapy must not have a non-acceptable drug interaction with protocol treatment. * For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Suppressive therapy must not have a non-acceptable drug interaction with protocol treatment. * Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Ongoing antiviral therapy must not have a non-acceptable drug interaction with protocol treatment. * Participants with a malignancy in remission are eligible for this trial. * Participants with known history or current symptoms of cardiac disease should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better. * The effects of filgrastim on the developing human fetus are unknown. For this reason and because decitabine is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of decitabine administration. * Ability to understand and the willingness to sign a written informed consent document.	* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 2) except for bone marrow suppression. * Participants should not be enrolled on another study that prohibits initiation of maintenance therapy. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine or filgrastim. * Participants with uncontrolled intercurrent illness. * Participant who are not able to present for clinic visits for at least 7 months after study treatment initiation. * Participant with FLT3/ITD mutations are excluded as maintenance therapy with tyrosine kinase therapy should be considered in this context. * Participants with a concurrent active malignancy are not eligible for this trial.

Inclusion Criteria

Exclusion Criteria

* Disease Criteria: Participants must have a histologically confirmed diagnosis of one of the following hematologic malignancies for eligibility, as defined by the criteria below:
* AML (relapsed, de-novo or secondary) based on WHO classification
* MDS (relapsed, de-novo or secondary) based on WHO classification
* Treatment myeloid neoplasm (tMDS/AML; relapsed disease included)
* Note: MDS, AML, MDS/AML, or tMDS/AML as defined above may be idiopathic/de novo or derived from a germline predisposition to myeloid malignancy. For patients with an underlying germline disorder, those conditions that are not associated with increased risk for toxicity to treatment, including patients with known germline ANKRD26, DDX41, ELANE and other congenital neutropenia disorders, ETV6, GATA-2, Li-Fraumeni, RUNX1, SAMD9/SAMD9L, or Shwachman-Diamond Syndrome, will be analyzed within the general treatment cohort (Cohort A, see Table 1) along with patients with idiopathic disease (Cohort B, see Table 2).
* Dyskeratosis Congenita or associated telomeropathies as defined by telomere length \<1st percentile on 3 out of 4 lymphocyte subsets and/or corresponding pathogenic genetic mutation.
* Fanconi Anemia as defined by positive chromosomal breakage test to DEB/MMC and/or corresponding pathogenic genetic mutation.
* Nijmegen Breakage Syndrome as defined by positive chromosomal breakage test to DEB/MMC and/or corresponding pathogenic genetic mutation
* ERCC6L2 by genomic testing.
* germline mutations in ANKRD26
* germline mutations in DDX41
* ELANE and other Congenital Neutropenia Disorders
* germline mutations in ETV6
* germline mutations in GATA-2
* Li-Fraumeni
* germline mutations in RUNX1
* SAMD9/SAMD9L
* Shwachman-Diamond Syndrome
* Familial MDS with thrombocytopenia
* Diamond-Blackfan Anemia
* iBMF with Increased Risk for Treatment Related Toxicities:
* Fanconi Anemia
* Dyskeratosis Congenita and associated Telomere Disorders
* Nijmegen Breakage Syndrome
* ERCC6L2
* Patients must be receiving an allogeneic hematopoietic stem cell transplant. All donor types and graft sources are permitted. All conditioning regimens are permitted. All GVHD prophylaxis regimens are permitted.
* Timing of Enrollment: Registration can occur from day - 30 to day - 10 prior to stem cell infusion.
* Disease Status: Study enrollment will occur pre HCT. Any disease status is acceptable at the time of enrollment; however, patients must be in a MRD negative remission (as defined by multidimensional flow cytometry (MDF) post HCT prior to protocol treatment start). Post HCT/ pretreatment disease status will be performed by Hematologics.
* No limitations on prior therapy.
* Age ≥1 year and ≤ 39 year of age.
* ECOG performance status ≤2 (Lansky, Karnofsky ≥60%).
* Participants must have adequate organ function to be eligible for allogenic HCT as per institutional standard.
* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Anti- retroviral therapy must not have a non-acceptable drug interaction with protocol treatment.
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Suppressive therapy must not have a non-acceptable drug interaction with protocol treatment.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Ongoing antiviral therapy must not have a non-acceptable drug interaction with protocol treatment.
* Participants with a malignancy in remission are eligible for this trial.
* Participants with known history or current symptoms of cardiac disease should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
* The effects of filgrastim on the developing human fetus are unknown. For this reason and because decitabine is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of decitabine administration.
* Ability to understand and the willingness to sign a written informed consent document.

* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 2) except for bone marrow suppression.
* Participants should not be enrolled on another study that prohibits initiation of maintenance therapy.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine or filgrastim.
* Participants with uncontrolled intercurrent illness.
* Participant who are not able to present for clinic visits for at least 7 months after study treatment initiation.
* Participant with FLT3/ITD mutations are excluded as maintenance therapy with tyrosine kinase therapy should be considered in this context.
* Participants with a concurrent active malignancy are not eligible for this trial.

Contacts and Locations

Study Contact

Franziska Wachter, MD

CONTACT

617-632-4583

franziska_wachter@dfci.harvard.edu

Principal Investigator

Franziska Wachter, MD

PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Study Locations (Sites)

Boston Children's Hospital

Boston, Massachusetts, 02215

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Collaborators and Investigators

Sponsor: Franziska Wachter

Franziska Wachter, MD, PRINCIPAL_INVESTIGATOR, Dana-Farber Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-04-19

Study Completion Date2029-09-01

Study Record Updates

Study Start Date2023-04-19

Study Completion Date2029-09-01

Terms related to this study

Keywords Provided by Researchers

Acute Myeloid Leukemia
Myelodysplastic Syndromes
Myeloid Malignancies
MDS
Inherited Bone Marrow Failure Syndrome
Myeloid Neoplasm
AML

Additional Relevant MeSH Terms

Acute Myeloid Leukemia
Myelodysplastic Syndromes
Myeloid Malignancies
MDS
Inherited Bone Marrow Failure Syndrome
Myeloid Neoplasm
Aml