Leukemia, Myeloid, AcutePhase 1AML MDSNCT00986804
Decitabine Maintenance for Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS) Post Transplant
A Phase 1 study testing Decitabine in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Primary: To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after allogeneic hematopoietic stem cell transplantation (alloHSCT) performed for AML or high-risk MDS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
- What is being tested?
- Decitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Feb 2016
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of AML or MDS using WHO classification.
- >50 and <100 days following HLA-matched related or unrelated donor alloHSCT. Donors may be mismatched at single antigen at HLA-A, -B or -DR locus plus possible single antigen mismatch at HLA-C according to institution guidelines. Two-antigen mismatch at a single locus is not allowed.
- Age >=18 years.
- Bone marrow biopsy confirming complete remission after alloHSCT
- o Complete remission: less than 5% blasts in an aspirate bone marrow sample with a count of at least 200 nucleated cells, no blasts with Auer rods or persistence of extramedullary disease PLUS absolute neutrophil count (ANC) > 1,500/μL, platelet count ≥ 50,000/μL and no leukemic blasts in the peripheral blood.
- Platelet count ≥ 50,000/µL without platelet transfusion for 7 days and ANC ≥ 1,500/µL without colony stimulating factor support.
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- Performance status < ECOG 2.
- Acceptable organ function defined as:
- creatinine < 1.5 times the institutional ULN or creatinine clearance (calculated by the Cockroft and Gault method) ≥ 30 mL/min
- bilirubin < 1.5 times the institutional ULN
- AST, ALT and alkaline phosphatase < 2.5 times the institutional ULN.
- Each Patient or their legal authorized representative must sign an institutional review board/ethics committee-approved informed consent indicating their awareness of the investigational nature of this study.
- Female Subjects:
- Female of childbearing potential (FCBP*) must agree to use a reliable form of contraception or to practice complete abstinence from heterosexual intercourse for at least 28 days before starting study drug, while participating in the study, and for at least 28 days after discontinuation from the study. The methods of reliable contraception include intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation, partner's vasectomy, latex condom, diaphragm and cervical cap.
- FCBP must agree to pregnancy testing.
- FCBP must a negative pregnancy test prior to starting study drug.
- FCBP must agree to abstain from donating blood and/or egg during study participation and for at least 28 days after discontinuation from the study
- A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months).
- Male Subjects:
- Must agree to use a latex condom during sexual contact with FCBP while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy
- Must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from the study.
- Must agree that if a pregnancy or a positive pregnancy test does occur in a female partner of a male study subject during study participation, study drug must be immediately discontinued and must immediately notify the principal investigator.
Who cannot join
- History of previous alloHSCT prior to the current alloHSCT.
- Persistent AML or MDS after alloHSCT.
- Grade 3- 4 acute GVHD, See Appendix A.
- Positive serology for HIV.
- Pregnancy or nursing.
- Other cancers less than or equal to 2 years prior study entry except: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, prostate cancer stage T1a or T1b.
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- Uncontrolled active infections requiring intravenous antibiotics.
- Clinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), which, in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate protocol therapy.
- Known or suspected hypersensitivity to decitabine.
- Patients may not be receiving any other investigational agents.
- General or specific changes in patient's condition that render the patient unacceptable for further treatment in judgment of the investigators.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Maintenance Therapy With Decitabine After Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome
Primary:
To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after allogeneic hematopoietic stem cell transplantation (alloHSCT) performed for AML or high-risk MDS.
Read the detailed description
Secondary:
- To determine the safety and tolerability of decitabine as maintenance therapy after alloHSCT.
- To determine the rates disease relapse, 1-year disease-free survival, and overall survival.
- To assess lymphoid and myeloid chimerism while on decitabine maintenance.
- To determine the incidence of acute and chronic GVHD.
- To assess immunologic reconstitution after alloHSCT.
- To assess changes in gene expression and methylation patterns following decitabine treatment
- To assess the effects of decitabine on immune reconstitution post transplant.
- To access the frequency of FoxP3+ CD3+/CD4+ and CD3+/CD8+ lymphocytes before and after decitabine treatment.
- Being tested
- Decitabine
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called Dacogen
| Study group | Role | What they receive |
|---|---|---|
| Level 1 | Experimental | Decitabine 5.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles. Receives: Drug: Decitabine |
| Level 2 | Experimental | Decitabine 7.5 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles. Receives: Drug: Decitabine |
| Level 3 | Experimental | Decitabine 10.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles. Receives: Drug: Decitabine |
| Level 4 | Experimental | Decitabine 15.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles. Receives: Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after alloHSCT performed for AML or high-risk MDS.
Measured: Up to 6 weeks (completion of first cycle)
Secondary outcomes (11)
To determine the safety and tolerability of decitabine as maintenance therapy after alloHSCT.
Measured: Up to 30 days after end of study (approximately 46 weeks)
To determine the rates disease relapse
Measured: Every 3 months for 2 years then every 6 months for 3 years
To assess lymphoid and myeloid chimerism while on decitabine maintenance.
Measured: End of cycle 3 (18 weeks)
To determine the incidence of acute GVHD.
Measured: End of study (42 weeks)
To assess immunologic reconstitution after alloHSCT.
Measured: End of study (42 weeks)
To assess changes in gene expression and methylation patterns following decitabine treatment
Measured: End of study (42 weeks)
To assess the effects of decitabine on immune reconstitution post transplant.
Measured: End of study (42 weeks)
To access the frequency of FoxP3+ CD3+/CD4+ and CD3+/CD8+ lymphocytes before and after decitabine treatment.
Measured: End of cycle 3 (18 weeks)
To determine the 1-year disease-free survival
Measured: 1 year
To determine overall survival.
Measured: Every 3 months for 2 years then every 6 months for 3 years
To determine the incidence of chronic GVHD.
Measured: End of study (42 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2009 (estimated)
- Study startDec 2009
- Primary completionMay 2014
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Iskra Pusic, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00986804
- Sponsor's protocol ID
- 09-1126 / 201108378
- Acronym
- AML MDS
- Status last verified
- Feb 2016
- First submitted
- 29 Sep 2009
- Last updated
- 15 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Blum W, Bruner-Klisovic R, Liu S, et al. Phase I Study of Low Dose Decitabine in Patients with Acute Myeloid Leukemia (AML): Pharmacokinetics (PK), Pharmacodynamics (PD), and Clinical Activity. ASH Annual Meeting Abstracts. 2005;106:1861-.
Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R 3rd, Shen L, Nimer SD, Leavitt R, Raza A, Saba H. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006 Apr 15;106(8):1794-803. doi: 10.1002/cncr.21792.
PubMed 16532500Choi J, Ritchey J, DiPersio J. Generation of Treg-Like Cells from CD4+CD25- T Cells Via Epigenetic Modification Using a Demethylating Agent Decitabine. ASH Annual Meeting Abstracts. 2007;110:62-.
De Lima M, de Padua Silva L, Giralt S, et al. Maintenance Therapy with Low-Dose Azacitidine (AZA) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Relapsed or Refractory AML or MDS: A Dose and Schedule Finding Study. ASH Annual Meeting Abstracts. 2008;112:1134-.
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maintenance Therapy With Decitabine After Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT00986804
- Acronym / sponsor ID
- AML MDS / 09-1126 / 201108378
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- May 2014 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 30 Sep 2009 (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.
Primary:
To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after allogeneic hematopoietic stem cell transplantation (alloHSCT) performed for AML or high-risk MDS.
Detailed description
Secondary:
- To determine the safety and tolerability of decitabine as maintenance therapy after alloHSCT.
- To determine the rates disease relapse, 1-year disease-free survival, and overall survival.
- To assess lymphoid and myeloid chimerism while on decitabine maintenance.
- To determine the incidence of acute and chronic GVHD.
- To assess immunologic reconstitution after alloHSCT.
- To assess changes in gene expression and methylation patterns following decitabine treatment
- To assess the effects of decitabine on immune reconstitution post transplant.
- To access the frequency of FoxP3+ CD3+/CD4+ and CD3+/CD8+ lymphocytes before and after decitabine treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Level 1 | Experimental | Drug: DecitabineDecitabine 5.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles. |
| Level 2 | Experimental | Drug: DecitabineDecitabine 7.5 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles. |
| Level 3 | Experimental | Drug: DecitabineDecitabine 10.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles. |
| Level 4 | Experimental | Drug: DecitabineDecitabine 15.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- History of AML or MDS using WHO classification.
- >50 and <100 days following HLA-matched related or unrelated donor alloHSCT. Donors may be mismatched at single antigen at HLA-A, -B or -DR locus plus possible single antigen mismatch at HLA-C according to institution guidelines. Two-antigen mismatch at a single locus is not allowed.
- Age >=18 years.
- Bone marrow biopsy confirming complete remission after alloHSCT
- o Complete remission: less than 5% blasts in an aspirate bone marrow sample with a count of at least 200 nucleated cells, no blasts with Auer rods or persistence of extramedullary disease PLUS absolute neutrophil count (ANC) > 1,500/μL, platelet count ≥ 50,000/μL and no leukemic blasts in the peripheral blood.
Key exclusion criteria (11 listed)
- History of previous alloHSCT prior to the current alloHSCT.
- Persistent AML or MDS after alloHSCT.
- Grade 3- 4 acute GVHD, See Appendix A.
- Positive serology for HIV.
- Pregnancy or nursing.
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: Dacogen | Drug | Level 1, Level 2, Level 3, Level 4 |
Primary outcome
To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after alloHSCT performed for AML or high-risk MDS.
Time frame: Up to 6 weeks (completion of first cycle)
11 secondary outcomes
To determine the safety and tolerability of decitabine as maintenance therapy after alloHSCT.
Time frame: Up to 30 days after end of study (approximately 46 weeks)
To determine the rates disease relapse
Time frame: Every 3 months for 2 years then every 6 months for 3 years
To assess lymphoid and myeloid chimerism while on decitabine maintenance.
Time frame: End of cycle 3 (18 weeks)
To determine the incidence of acute GVHD.
Time frame: End of study (42 weeks)
To assess immunologic reconstitution after alloHSCT.
Time frame: End of study (42 weeks)
To assess changes in gene expression and methylation patterns following decitabine treatment
Time frame: End of study (42 weeks)
To assess the effects of decitabine on immune reconstitution post transplant.
Time frame: End of study (42 weeks)
To access the frequency of FoxP3+ CD3+/CD4+ and CD3+/CD8+ lymphocytes before and after decitabine treatment.
Time frame: End of cycle 3 (18 weeks)
To determine the 1-year disease-free survival
Time frame: 1 year
To determine overall survival.
Time frame: Every 3 months for 2 years then every 6 months for 3 years
To determine the incidence of chronic GVHD.
Time frame: End of study (42 weeks)
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 Feb 2016.
- BackgroundBlum W, Bruner-Klisovic R, Liu S, et al. Phase I Study of Low Dose Decitabine in Patients with Acute Myeloid Leukemia (AML): Pharmacokinetics (PK), Pharmacodynamics (PD), and Clinical Activity. ASH Annual Meeting Abstracts. 2005;106:1861-.
- Background: PubMed 16532500Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R 3rd, Shen L, Nimer SD, Leavitt R, Raza A, Saba H. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006 Apr 15;106(8):1794-803. doi: 10.1002/cncr.21792.
- BackgroundChoi J, Ritchey J, DiPersio J. Generation of Treg-Like Cells from CD4+CD25- T Cells Via Epigenetic Modification Using a Demethylating Agent Decitabine. ASH Annual Meeting Abstracts. 2007;110:62-.
- BackgroundDe Lima M, de Padua Silva L, Giralt S, et al. Maintenance Therapy with Low-Dose Azacitidine (AZA) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Relapsed or Refractory AML or MDS: A Dose and Schedule Finding Study. ASH Annual Meeting Abstracts. 2008;112:1134-.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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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.
Iskra Pusic, M.D. principal investigator
Washington University School of Medicine
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, Myeloid, Acute and Myelodysplastic Syndromes, run by Washington University School of Medicine 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 22 inclusion and 11 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 Feb 2016. 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?
To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after alloHSCT performed for AML or high-risk MDS. (time frame: Up to 6 weeks (completion of first cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00986804, which also lists 4 linked publications.
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 Feb 2016.