Chronic Myeloproliferative DisordersPhase 1NCT00114257
Decitabine and FR901228 in Treating Patients With Relapsed or Refractory Leukemia, Myelodysplastic Syndromes, or Myeloproliferative Disorders
A Phase 1 study testing decitabine and romidepsin in people with Chronic Myeloproliferative Disorders and Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of decitabine and FR901228 in treating patients with relapsed or refractory leukemia, myelodysplastic syndromes or myeloproliferative disorders. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes
- What is being tested?
- decitabine and romidepsin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Sep 2006
- 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
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following hematologic malignancies:
- Acute myeloid leukemia
- Previously untreated patients > 60 years of age who are not eligible for front-line therapy are eligible for this study
- Acute lymphoblastic leukemia
- Chronic myelogenous leukemia (CML)
- Documented hematologic resistance to imatinib mesylate OR no cytogenetic response after 12 months of prior treatment with imatinib mesylate
- Philadelphia chromosome-negative CML allowed provided disease is resistant to standard therapy (e.g., hydroxyurea) OR disease progressed (blasts > 5% and platelet count < 100,000/mm^3) during standard therapy
- Myelodysplastic syndromes
- International Prognostic Scoring System risk category ≥ intermediate-1
- Patients who are not eligible for front-line therapy are eligible for this study
- Myeloproliferative disease
- Chronic lymphocytic leukemia
- Failed or progressed during ≥ 1 prior fludarabine-based therapy AND alemtuzmab
- Acute promyelocytic leukemia
- Progressed after prior treatment with standard chemotherapy, tretinoin, and arsenic trioxide
- Chronic myelomonocytic leukemia
- Resistant to standard therapy (e.g., hydroxyurea) OR disease progressed (blasts > 5% and platelet count < 100,000/mm^3) during standard therapy
- Relapsed or refractory disease
- No known brain or meningeal disease
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- ECOG 0-1
Life expectancy
- More than 8 weeks
Hepatic
- Bilirubin < 2 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal
Renal
- Creatinine < 2 mg/dL
Cardiovascular
- QTc < 500 msec
- LVEF > 40% by MUGA
- No New York Heart Association class III or IV congestive heart failure
- No myocardial infarction within the past year
- No uncontrolled dysrhythmias
- No uncontrolled angina
- No left ventricular hypertrophy by EKG
- No history of serious ventricular arrhythmia (e.g., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
- No other significant cardiac disease
Immunologic
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs
- No ongoing or active infection
- No HIV positivity
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
PRIOR CONCURRENT THERAPY:
Chemotherapy
- Recovered from prior chemotherapy
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) unless there is evidence of rapidly progressive disease
Radiotherapy
- At least 4 weeks since prior radiotherapy and recovered
Other
- No concurrent agents that cause QTc prolongation
- No other concurrent investigational or commercial agents or therapies for the malignancy
- No concurrent hydrochlorothiazide
- Concurrent potassium-conserving combinations (e.g., Maxide® or Dyazide®) or other antihypertensive agents allowed
Trial locations and contacts
1 site in 1 country.
United States1 site
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
About this study
Official title: A Phase I Study of 5-AZA-2'-Deoxycytidine and Depsipeptide in Patients With Relapsed/Refractory Leukemia, Myelodysplastic Syndromes, or Myeloproliferative Disease
This phase I trial is studying the side effects and best dose of decitabine and FR901228 in treating patients with relapsed or refractory leukemia, myelodysplastic syndromes or myeloproliferative disorders. Drugs used in chemotherapy, such as decitabine and FR901228, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. FR901228 may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving decitabine together with FR901228 may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose and recommended phase II dose of decitabine and FR901228 (depsipeptide) in patients with relapsed or refractory leukemia, myelodysplastic syndromes, or myeloproliferative disease.
II. Determine the safety and tolerability of this regimen in these patients.
SECONDARY OBJECTIVES:
- Determine the clinical activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive decitabine IV over 1 hour on days 1-5 and 8-12 and FR901228 (depsipeptide) IV over 4 hours on days 5 and 12 OR days 5, 12, and 19. Treatment repeats every 4-6 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing complete remission for 1 year are removed from the study.
Cohorts of 6 patients receive escalating doses of decitabine and FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
- Being tested
- decitabine, romidepsin
- Keywords
- recurrent adult acute lymphoblastic leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent adult acute myeloid leukemia, secondary acute myeloid leukemia, untreated adult acute myeloid leukemia, adult acute promyelocytic leukemia (M3), relapsing chronic myelogenous leukemia, refractory chronic lymphocytic leukemia, de novo myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm, unclassifiable, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, atypical chronic myeloid leukemia, BCR-ABL1 negative, chronic myelomonocytic leukemia, chronic eosinophilic leukemia, primary myelofibrosis
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Congenital Abnormalities, Leukemia, Myeloid, Acute, Leukemia, Promyelocytic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
decitabineDrug
romidepsinDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive decitabine IV over 1 hour on days 1-5 and 8-12 and FR901228 (depsipeptide) IV over 4 hours on days 5 and 12 OR days 5, 12, and 19. Treatment repeats every 4-6 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing complete remission for 1 year are removed from the study.
Cohorts of 6 patients receive escalating doses of decitabine and FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Receives: Drug: decitabine; Drug: romidepsin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity at 6 weeks after each course
Secondary outcomes (1)
Complete and partial response at 6 weeks after each course
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2005 (estimated)
- Study startMay 2005
- Primary completionSep 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jean-Pierre Issa, MD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00114257
- Sponsor's protocol ID
- NCI-2012-02657
- Other IDs
- MDA-2004-0674, NCI-5563, CDR0000433040
- Status last verified
- Sep 2006
- First submitted
- 13 Jun 2005
- Last updated
- 11 Feb 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of 5-AZA-2'-Deoxycytidine and Depsipeptide in Patients With Relapsed/Refractory Leukemia, Myelodysplastic Syndromes, or Myeloproliferative Disease
- ClinicalTrials.gov ID
- NCT00114257
- Acronym / sponsor ID
- NCI-2012-02657
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
- Keywords
- recurrent adult acute lymphoblastic leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent adult acute myeloid leukemia, secondary acute myeloid leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 2005
- Primary completion
- Sep 2006 (actual)
- First posted
- 14 Jun 2005 (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.
This phase I trial is studying the side effects and best dose of decitabine and FR901228 in treating patients with relapsed or refractory leukemia, myelodysplastic syndromes or myeloproliferative disorders. Drugs used in chemotherapy, such as decitabine and FR901228, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. FR901228 may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving decitabine together with FR901228 may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose and recommended phase II dose of decitabine and FR901228 (depsipeptide) in patients with relapsed or refractory leukemia, myelodysplastic syndromes, or myeloproliferative disease.
II. Determine the safety and tolerability of this regimen in these patients.
SECONDARY OBJECTIVES:
- Determine the clinical activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive decitabine IV over 1 hour on days 1-5 and 8-12 and FR901228 (depsipeptide) IV over 4 hours on days 5 and 12 OR days 5, 12, and 19. Treatment repeats every 4-6 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing complete remission for 1 year are removed from the study.
Cohorts of 6 patients receive escalating doses of decitabine and FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: decitabine, Drug: romidepsinPatients receive decitabine IV over 1 hour on days 1-5 and 8-12 and FR901228 (depsipeptide) IV over 4 hours on days 5 and 12 OR days 5, 12, and 19. Treatment repeats every 4-6 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing complete remission for 1 year are removed from the study. Cohorts of 6 patients receive escalating doses of decitabine and FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| decitabine | Drug | Arm I |
| romidepsin | Drug | Arm I |
Primary outcome
Toxicity at 6 weeks after each course
1 secondary outcome
Complete and partial response at 6 weeks after each course
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 11 Feb 2013.
Related trials for Chronic Myeloproliferative Disorders
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid 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.
Jean-Pierre Issa, MD study chair
M.D. Anderson Cancer Center
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 and romidepsin in people with Chronic Myeloproliferative Disorders and Leukemia, run by National Cancer Institute (NCI) 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?
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 11 Feb 2013. 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?
Toxicity at 6 weeks after each course. 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 11 Feb 2013.