Trial 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
NCT ID:
NCT05796570
Condition:
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Myeloid Malignancies
MDS
Inherited Bone Marrow Failure Syndrome
Myeloid Neoplasm
Aml
Conditions: Official terms:
Neoplasms
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Bone Marrow Failure Disorders
Pancytopenia
Congenital Bone Marrow Failure Syndromes
Syndrome
Decitabine
Lenograstim
Conditions: Keywords:
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Myeloid Malignancies
MDS
Inherited Bone Marrow Failure Syndrome
Myeloid Neoplasm
AML
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Decitabine
Description:
Nucleoside metabolic inhibitor, via IV infusion.
Arm group label:
Cohort A: Standard Risk
Arm group label:
Cohort B: inherited bone marrow failure (iBMF) with Increased Risk for treatment related toxicities
Other name:
Dacogen
Intervention type:
Drug
Intervention name:
Filgrastim
Description:
Recombinant granulocyte colony-stimulating factor (G-CSF), via subcutaneous injection.
Arm group label:
Cohort A: Standard Risk
Arm group label:
Cohort B: inherited bone marrow failure (iBMF) with Increased Risk for treatment related toxicities
Other name:
Nivestym, Granix, Zarxio, Neupogen, Filgrastim-aafi, Filgrastim-sndz, Tbo-filgrastim, Rhg-csf
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)
Detailed description:
This is a single arm, pilot study to determine if sequential cycles of maintenance
therapy with decitabine and filgrastim post allogenic hematopoietic cell transplant (HCT)
are feasible and effective in preventing relapse after HCT in pediatric and young adult
patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and treatment
related myeloid malignancies (tAML/MDS) with either idiopathic disease or underlying
germline disorders, including a subset that may be at higher risk for toxicity from
treatment.
Decitabine in combination with filgrastim after stem cell transplant has been shown to be
effective in a large study that included mainly adult patients with acute myeloid
leukemia.
The research study procedures include screening for eligibility, study treatment
including evaluations and follow up visits and blood tests. Bone marrow biopsies and
aspirates will be performed as standard of care.
Participants will receive study treatment for 6 months if tolerated and will be followed
for 24 months after stem cell transplant.
It is expected about 37 people will take part in this research study.
This research study is supported by Dana-Farber Cancer Institute philanthropy and
institutional grants from the Dana-Farber Cancer Institute and Boston Children's
Hospital.
Criteria for eligibility:
Criteria:
Inclusion 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).
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
- 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
Table 2: Overview Inherited Bone Marrow Failure syndromes (iBMF)
- 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.
Exclusion Criteria:
- 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.
Gender:
All
Minimum age:
1 Year
Maximum age:
39 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Boston Children's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Franziska Wachter, MD
Phone:
617-632-4583
Email:
Franziska_Wachter@dfci.harvard.edu
Contact backup:
Last name:
Franziska Wachter
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Franziska Wachter, MD
Phone:
617-632-4583
Email:
franziska_wachter@dfci.harvard.edu
Start date:
April 19, 2023
Completion date:
September 1, 2029
Lead sponsor:
Agency:
Franziska Wachter
Agency class:
Other
Collaborator:
Agency:
Harvard Clinical and Translational Science Center (Harvard Catalyst)
Agency class:
Other
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05796570
