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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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
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

Other trials in United States

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:

  1. 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:

  1. 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.

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.

Study groups in NCT00114257
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.

  1. Toxicity at 6 weeks after each course

Secondary outcomes (1)
  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.

  1. First posted14 Jun 2005 (estimated)
  2. Study startMay 2005
  3. Primary completionSep 2006

Resources

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)
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

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.

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