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

NCT05796570 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-569
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

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)

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Feasibility Failure Rate (FFR)

  Feasibility failure relates to decitabine exposure in the setting of post-hematopoietic stem cell transplant (HCT) maintenance and in combination with filgrastim; FFR is defined as the proportion of participants that do not initiate at least 5 of 6 planned cycles and/or receive fewer than 22/30 overall planned decitabine doses during maintenance phase.

  Treatment duration up to 6 cycles (28 days/cycle) or 168 days

Secondary Outcomes (3)

• 24-Month Probability Event-Free Survival (EFS)

  Up to 24 months

• 24-Month Probability Overall Survival (OS)

  Up to 24 months

• Treatment Tolerability Rate (TTR)

  Up to the end of cycle 6 (28 days/cycle), or 168 days + 36 days post-treatment

Study Arms (2)

Cohort A: Standard Risk

EXPERIMENTAL

Participants with MDS, AML, AML/MDS, treatment related myeloid neoplasm (tAML/MDS) with either idiopathic disease or inherited bone marrow failure syndrome (iBMF) with standard risk for treatment related toxicities will be enrolled and will undergo study procedures as outlined: * Cycles 1: Study treatment start must occur 40 - 120 days post allogenic HCT. * Day 2 - 6 of 28-day cycle: Predetermined dose of Decitabine. * Day 1 - 6 of 28-day cycle: Predetermined dose of Filgrastim. * Cycles 2 - 6: * Day 2 - 6 of 28-day cycle: Predetermined dose of Decitabine. * Day 1 - 6 of 28-day cycle: Predetermined dose of Filgrastim. * Follow up visit every 6 months for 24 months post allogenic HCT.

Drug: Decitabine; Drug: Filgrastim

Cohort B: inherited bone marrow failure (iBMF) with Increased Risk for treatment related toxicities

EXPERIMENTAL

Participants with MDS, AML, AML/MDS, tAML/MDS with iBMF with increased risk for treatment related toxicities will be enrolled and will undergo study procedures as outlined: * Cycles 1: Study treatment must occur 40 - 120 days post allogenic HCT. * Day 2 - 6 of 28-day cycle: Predetermined dose of Decitabine. * Day 1 - 6 of 28-day cycle: Predetermined dose of Filgrastim. * Cycles 2 - 6: * Day 2 - 6 of 28-day cycle: Predetermined dose of Decitabine. * Day 1 - 6 of 28-day cycle: Predetermined dose of Filgrastim. * Follow up visit every 6 months for 24 months post allogenic HCT.

Drug: Decitabine; Drug: Filgrastim

Interventions

Decitabine DRUG

Nucleoside metabolic inhibitor, via IV infusion.

Also known as: Dacogen

Cohort A: Standard Risk; Cohort B: inherited bone marrow failure (iBMF) with Increased Risk for treatment related toxicities

Filgrastim DRUG

Recombinant granulocyte colony-stimulating factor (G-CSF), via subcutaneous injection.

Also known as: Nivestym, Granix, Zarxio, Neupogen, Filgrastim-aafi, Filgrastim-sndz, Tbo-filgrastim, Rhg-csf

Cohort A: Standard Risk; Cohort B: inherited bone marrow failure (iBMF) with Increased Risk for treatment related toxicities

Eligibility Criteria

• Age: 1 Year - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• Myeloid Sarcoma
• Acute Undifferentiated Leukemia (MPAL and acute leukemia of ambiguous lineage/NOS not eligible)
• 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).
• MDS, AML, MDS/AML, or tMDS/AML derived from the following germline disorders will be enrolled in a separate cohort (B) and adverse events monitored closely for higher rates compared to cohort A:
• 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.
• Table 2: Overview Inherited Bone Marrow Failure syndromes (iBMF)
• iBMF with Standard risk for Treatment Related toxicities:
• germline mutations in ANKRD26

You may not qualify if:

• 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. However, if a participant has a co-occurring NUP28 mutation, they will be considered eligible.
• Participants with a concurrent active malignancy are not eligible for this trial.

Sponsors & Collaborators

• Franziska Wachter: lead
• Harvard Clinical and Translational Science Center (Harvard Catalyst): collaborator

Study Sites (2)

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Congenital Bone Marrow Failure Syndromes

Interventions

Decitabine; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Bone Marrow Failure Disorders; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Franziska Wachter, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Franziska Wachter, MD

CONTACT

617-632-4583; franziska_wachter@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: April 3, 2023
• Study Start: April 19, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)