Leukemia, Lymphoblastic, AcutePhase 1NCT02264873
Phase I, Dose Escalation Study of Decitabine
A Phase 1 study testing Decitabine in people with Leukemia, Lymphoblastic, Acute and Leukemia, Myeloid Acute, run by University of Florida at 1 site in United States.
Trial summary
Decitabine is a hypomethylating agent that has shown significant anti-leukemic effect in Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukemia (AML). This study is based on the hypothesis that Decitabine delivered after allo-hematopoietic stem cell transplant (HSCT) in patients with leukemia will enhance… Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Leukemia, Lymphoblastic, Acute, Leukemia, Myeloid Acute, Hematopoetic Myelodysplasia
- What is being tested?
- Decitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to 18 Sep 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: greater than 1 and less than 31 years of age;
- Diagnosis: history of ALL, AML or MDS, currently in a complete remission (CR) following allo-HSCT (bone marrow leukemic blasts less than 5% by morphology), with high risk features including:
- Status post allogeneic HSCT
- GVHD prophylaxis:
- Karnofsky or Lansky performance scores more than 50%. Karnofsky scores will be used for patients > 16 years of age and Lansky scores for patients ≤ 16 years of age;
- Platelet count ≥ 50,000 (untransfused);
- Absolute neutrophil count ≥ 1000; and;
- Hemoglobin ≥ 8 g/dL (un-transfused);
Who cannot join
- Progressive disease;
- Philadelphia chromosome positive ALL (these patients receive tyrosine kinase inhibitor posttransplant);
- Known hypersensitivity to any components of decitabine;
- Uncontrolled grade 3-4 graft versus host disease;
- Uncontrolled infection;
- Serum creatinine > 2 mg/dL or glomerular filtration rate (GFR) less than 60 mL/min/1.73m2 ;
- Alanine Aminotransferase (ALT) greater than 3 times normal or serum total bilirubin greater than 2 mg/dL;
Trial locations and contacts
1 site in 1 country.
United States1 site
UF Health Shands Hospital
Gainesville, Florida, 32610
About this study
Official title: Minimizing Leukemia Relapse: A Phase I, Dose Escalation Study of Decitabine in High Risk Pediatric Leukemia Post Allogeneic Transplant
Decitabine is a hypomethylating agent that has shown significant anti-leukemic effect in Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukemia (AML). This study is based on the hypothesis that Decitabine delivered after allo-hematopoietic stem cell transplant (HSCT) in patients with leukemia will enhance disease control by the allogeneic immune system and lead to a longer disease free survival. The study is designed to provide safety data of low-dosing in the post-transplant setting.
Read the detailed description
Decitabine is a hypomethylating agent with significant anti-leukemic effect in MDS and AML. Additionally, aberrant DNA methylation has been identified in high risk childhood ALL, and therefore, DNA hypomethylating agents, such as decitabine, have been identified as therapeutic agents. Moreover, decitabine has immunomodulatory effects by enhancement of class I human leukocyte antigen (HLA) antigen expression on cancer cells, which increases their susceptibility to immune surveillance mechanisms, such as graft-versus-leukemia effect of donor cells in allogeneic transplantation and by augmentation of natural killer (NK), T and B lymphocyte reactivity. We hypothesize that decitabine delivered after allo-HSCT in patients with leukemia will enhance disease control by the allogeneic immune system and lead to a longer disease free survival. However, a safety study is needed to determine appropriate decitabine dosing in the post-transplant period. Low doses of decitabine are likely better tolerated in the post-transplant setting given risks of myelosuppression. In addition, when administered at lower doses, decitabine's hypomethylation effects are more pronounced in relation to its pyrimidine analog cytotoxic effects. In this study low doses of decitabine will be administered beginning 6 weeks to 100 days post-transplant. Measures of gene methylation and immune reconstitution will be conducted to define biologically active doses. Results from this trial will provide new clinical data regarding the effects of decitabine on gene methylation and immunoreactivity, will establish a maximally tolerated dose in the post-transplant setting, will define biologically active doses, and will serve as a basis for future efficacy trials.
- Being tested
- Decitabine
- Keywords
- Relapse, Autologous stem cell transplant
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called Decitabine, Dacogen
Dose escalation starting at 5 mg, and increasing by 2.5 mg to a Dose Level of 12.5 mg qd x 3 days.
| Study group | Role | What they receive |
|---|---|---|
| Decitabine | Other | This is a 3+3 design of dose escalation Receives: Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose as a Measure of Safety and Tolerability
This is a dose escalation study of decitabine maintenance therapy after allo-HSCT for the maximally tolerated dose in pediatric patients without adverse events.
Measured: 3 months
Secondary outcomes (2)
Adverse Event Profile After Single Cycle Decitabine Post Transplant
The adverse events will be graded using the NCI Scale after one cycle of decitabine maintenance therapy intravenously. Grade 1 and 2 are unexpected and expect but unlikely related or unrelated; Grade 3 unexpected with hospitalization within 10 calendar days or possibly, probable related and without hospitalization; Grade 3 expected with hospitalization within 10 days or without hospitalization; Grade 4 and 5 Unexpected and Expected 24-hours to 5 days unlikely, unrelated, possible, probable, definite.
Measured: 6 months
Grade 3 Adverse Events after Decitabine
To estimate the incidences of ≥ grade 3 adverse events, infections, need for transfusions, treatment related mortality (TRM), and incidence and severity of graft vs host disease (GVHD) after initiation of decitabine post-HSCT. The grading will be done with the NCI Scale Grade 3 unexpected with hospitalization within 10 calendar days or possibly, probable related and without hospitalization; Grade 3 expected with hospitalization within 10 days or without hospitalization.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2014 (estimated)
- Study startOct 2014
- Primary completionOct 2016
- Study completion18 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Lymphoblastic, AcuteStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Hyundai Hope On Wheels
- Responsible party
- Sponsor
- Investigators
- Paul Castillo, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02264873
- Sponsor's protocol ID
- IRB201400612
- Other IDs
- PEDS004
- Status last verified
- Oct 2018
- First submitted
- 6 Oct 2014
- Last updated
- 15 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Minimizing Leukemia Relapse: A Phase I, Dose Escalation Study of Decitabine in High Risk Pediatric Leukemia Post Allogeneic Transplant
- ClinicalTrials.gov ID
- NCT02264873
- Acronym / sponsor ID
- IRB201400612
- Keywords
- Relapse, Autologous stem cell transplant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Hyundai Hope On Wheels
- Study start
- Oct 2014
- Primary completion
- Oct 2016 (actual)
- Study completion
- 18 Sep 2018 (actual)
- First posted
- 15 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Decitabine is a hypomethylating agent that has shown significant anti-leukemic effect in Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukemia (AML). This study is based on the hypothesis that Decitabine delivered after allo-hematopoietic stem cell transplant (HSCT) in patients with leukemia will enhance disease control by the allogeneic immune system and lead to a longer disease free survival. The study is designed to provide safety data of low-dosing in the post-transplant setting.
Detailed description
Decitabine is a hypomethylating agent with significant anti-leukemic effect in MDS and AML. Additionally, aberrant DNA methylation has been identified in high risk childhood ALL, and therefore, DNA hypomethylating agents, such as decitabine, have been identified as therapeutic agents. Moreover, decitabine has immunomodulatory effects by enhancement of class I human leukocyte antigen (HLA) antigen expression on cancer cells, which increases their susceptibility to immune surveillance mechanisms, such as graft-versus-leukemia effect of donor cells in allogeneic transplantation and by augmentation of natural killer (NK), T and B lymphocyte reactivity. We hypothesize that decitabine delivered after allo-HSCT in patients with leukemia will enhance disease control by the allogeneic immune system and lead to a longer disease free survival. However, a safety study is needed to determine appropriate decitabine dosing in the post-transplant period. Low doses of decitabine are likely better tolerated in the post-transplant setting given risks of myelosuppression. In addition, when administered at lower doses, decitabine's hypomethylation effects are more pronounced in relation to its pyrimidine analog cytotoxic effects. In this study low doses of decitabine will be administered beginning 6 weeks to 100 days post-transplant. Measures of gene methylation and immune reconstitution will be conducted to define biologically active doses. Results from this trial will provide new clinical data regarding the effects of decitabine on gene methylation and immunoreactivity, will establish a maximally tolerated dose in the post-transplant setting, will define biologically active doses, and will serve as a basis for future efficacy trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Decitabine | Other | Drug: DecitabineThis is a 3+3 design of dose escalation |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Age: greater than 1 and less than 31 years of age;
- Diagnosis: history of ALL, AML or MDS, currently in a complete remission (CR) following allo-HSCT (bone marrow leukemic blasts less than 5% by morphology), with high risk features including:
- Status post allogeneic HSCT
- GVHD prophylaxis:
- Karnofsky or Lansky performance scores more than 50%. Karnofsky scores will be used for patients > 16 years of age and Lansky scores for patients ≤ 16 years of age;
Key exclusion criteria (7 listed)
- Progressive disease;
- Philadelphia chromosome positive ALL (these patients receive tyrosine kinase inhibitor posttransplant);
- Known hypersensitivity to any components of decitabine;
- Uncontrolled grade 3-4 graft versus host disease;
- Uncontrolled infection;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DecitabineAlso: Decitabine, DacogenDose escalation starting at 5 mg, and increasing by 2.5 mg to a Dose Level of 12.5 mg qd x 3 days. | Drug | Decitabine |
Primary outcome
Maximum Tolerated Dose as a Measure of Safety and Tolerability
Time frame: 3 months
This is a dose escalation study of decitabine maintenance therapy after allo-HSCT for the maximally tolerated dose in pediatric patients without adverse events.
2 secondary outcomes
Adverse Event Profile After Single Cycle Decitabine Post Transplant
Time frame: 6 months
Grade 3 Adverse Events after Decitabine
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2018.
Related trials for Leukemia, Lymphoblastic, Acute
RecruitingPhase 2
Inotuzumab Ozogamicin and Blinatumomab With or Without Ponatinib in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia
B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, Recurrent B Acute Lymphoblastic Leukemia
Active, not recruitingPhase 3
Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
RecruitingPhase 1/2
CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies
B-NHL, B-Non Hodgkin Lymphoma
Recruiting
A Multicenter Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-Cell Recovery to Guide Management Following Chimeric Antigen Receptor T-cell (CART) Induced Remission in Children and Young Adults With B Lineage Acute Lymph...
B-All, Acute Lymphoblastic Leukemia
RecruitingPhase 2
Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases
Acute Leukemia of Ambiguous Lineage, Acute Lymphoblastic Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Castillo, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Decitabine in people with Leukemia, Lymphoblastic, Acute and Leukemia, Myeloid Acute, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose as a Measure of Safety and Tolerability (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2018; AzTrials last refreshed its copy on 26 Oct 2026.