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Acute Myeloid LeukemiaPhase 1NCT00101179

MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

A Phase 1 study testing Azacitidine and Entinostat in people with Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia, run by National Cancer Institute (NCI) at 3 sites 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

MS-275 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Azacitidine and Entinostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
3 sitesUnited States
Study dates
3 Nov 2004to 3 Feb 2014
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

  • Diagnosis of 1 of the following:
  • Histologically confirmed myelodysplastic syndromes (MDS) by bone marrow aspiration and/or biopsy
  • International Prognostic Scoring System (IPSS) score of intermediate-1, intermediate-2, or high
  • International Prognostic Scoring System (IPSS) score of intermediate-1, intermediate-2, or high
  • Low IPSS score allowed provided patient has a clinically significant cytopenia (i.e., absolute neutrophil count < 1,000/mm^3, untransfused hemoglobin < 8 g/dL, platelet count < 20,000/mm^3, or anemia requiring transfusion)
  • Chronic myelomonocytic leukemia
Show all 44Show fewer
  • Acute myeloid leukemia (AML)
  • Relapsed or refractory disease
  • Untreated AML allowed provided patient meets >= 1 of the following criteria:
  • Age 60 and over
  • AML arising in the setting of an antecedent hematologic disorder
  • High-risk cytogenetic abnormalities
  • Medical conditions that may compromise the ability to give cytotoxic chemotherapy as the primary modality
  • Refused cytotoxic chemotherapy
  • WBC < 30,000/mm3 for >= 2 weeks before study entry
  • Acute promyelocytic leukemia allowed provided patient is in at least second relapse and has already received treatment regimens containing arsenic trioxide and isotretinoin
  • No clinical evidence of CNS or pulmonary leukostasis or CNS leukemia
  • Peformance status:
  • Zubrod 0-2
  • Life expectancy:
  • At least 6 months
  • Hematopoietic:
  • See Disease Characteristics
  • Hemoglobin ≥ 8 g/dL (transfusion allowed)
  • No disseminated intravascular coagulation
  • Renal:
  • Creatinine normal OR
  • Creatinine clearance >= 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study treatment
  • No untreated, active infection
  • No other serious or uncontrolled medical condition
  • More than 3 weeks since prior hematopoietic growth factors for this malignancy
  • At least 3 weeks since prior hydroxyurea (2 weeks for AML patients)
  • No concurrent hydroxyurea
  • Recovered from all prior therapy
  • At least 2 weeks since prior cytotoxic therapy (AML patients)
  • More than 3 weeks since other prior therapy for this malignancy
  • No other concurrent investigational or commercial agents or therapies for this malignancy
  • No concurrent valproic acid
  • Hepatic:
  • Bilirubin normal unless due to hemolysis or Gilbert's syndrome
  • AST and ALT =< 2.5 times upper limit of normal

Who cannot join

None listed.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Mount Sinai Hospital

    New York, New York, 10029

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Dose-Finding Trial of the Histone Deacetylase Inhibitor MS-275 (NSC 706995) in Combination With 5-Azacitidine (5AC, NSC 102816) in Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMMoL) and Acute Myeloid Leukemia (AML)

MS-275 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving MS-275 together with azacitidine may kill more cancer cells. This phase I trial is studying the side effects and best dose of MS-275 when given together with azacitidine in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.

Read the detailed description

OBJECTIVES:

  1. Determine the safety and toxicity of MS-275 and azacitidine in patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.

II. Determine the maximum tolerated dose and optimal phase II dose of MS-275 when combined with azacitidine in these patients.

III. Determine, preliminarily, the potential therapeutic activity of this regimen in these patients.

IV. Correlate MS-275 pharmacokinetics with clinical response and laboratory correlative endpoints in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of MS-275. Patients receive azacitidine subcutaneously on days 1-10 and oral MS-275 on days 3 and 10.

Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of MS-275 until the maximum tolerated dose (MTD) is determined. Patients receive adjusted doses of azacitidine based on clinical response. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 9 additional patients are treated at the MTD.

[Note: Patients who do not achieve hematologic improvement or partial or complete response but who have stable disease after 4 courses of therapy may receive an additional 4 courses of therapy at a higher dose than what was originally assigned]

Being tested
Azacitidine, Entinostat
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Leukemia, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzacitidineDrug

    Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC

    Given SC

  • EntinostatDrug

    Also called HDAC inhibitor SNDX-275, MS 27-275, MS-275, SNDX-275

    Given orally

Study groups in NCT00101179
Study groupRoleWhat they receive
Arm IExperimentalPatients receive azacitidine subcutaneously on days 1-10 and oral MS-275 on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses* of MS-275 until the maximum tolerated dose (MTD) is determined. Patients receive adjusted doses of azacitidine based on clinical response. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 9 additional patients are treated at the MTD.
Receives: Drug: Azacitidine; Drug: Entinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose of MS-275 in combination with 5-azacitidine, assessed using Common Toxicity Criteria version 3.0

    Measured: 4 weeks

Secondary outcomes (3)

  1. Response rate measured by IWG criteria

    Measured: 16 weeks

  2. Optimal dose combination

    Measured: At study completion

  3. Levels of histone acetylation and gene re-expression

    Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2005 (estimated)
  2. Study start3 Nov 2004
  3. Primary completion20 Apr 2011
  4. Study completion3 Feb 2014

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
63 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00101179
Sponsor's protocol ID
NCI-2009-00071
Other IDs
NCI-2009-00071, CDR0000405841, J0443, J0443, 6591, P30CA006973, U01CA070095
Status last verified
Oct 2019
First submitted
7 Jan 2005
Last updated
18 Oct 2019
Results posted
No

Publications

  • Prebet T, Sun Z, Ketterling RP, Zeidan A, Greenberg P, Herman J, Juckett M, Smith MR, Malick L, Paietta E, Czader M, Figueroa M, Gabrilove J, Erba HP, Tallman MS, Litzow M, Gore SD; Eastern Cooperative Oncology Group and North American Leukemia intergroup. Azacitidine with or without Entinostat for the treatment of therapy-related myeloid neoplasm: further results of the E1905 North American Leukemia Intergroup study. Br J Haematol. 2016 Feb;172(3):384-91. doi: 10.1111/bjh.13832. Epub 2015 Nov 18.

    PubMed 26577691

  • Figueroa ME, Skrabanek L, Li Y, Jiemjit A, Fandy TE, Paietta E, Fernandez H, Tallman MS, Greally JM, Carraway H, Licht JD, Gore SD, Melnick A. MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation. Blood. 2009 Oct 15;114(16):3448-58. doi: 10.1182/blood-2009-01-200519. Epub 2009 Aug 3.

    PubMed 19652201

  • Fandy TE, Herman JG, Kerns P, Jiemjit A, Sugar EA, Choi SH, Yang AS, Aucott T, Dauses T, Odchimar-Reissig R, Licht J, McConnell MJ, Nasrallah C, Kim MK, Zhang W, Sun Y, Murgo A, Espinoza-Delgado I, Oteiza K, Owoeye I, Silverman LR, Gore SD, Carraway HE. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. Blood. 2009 Sep 24;114(13):2764-73. doi: 10.1182/blood-2009-02-203547. Epub 2009 Jun 22.

    PubMed 19546476

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Azacitidine and Entinostat in people with Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia, run by National Cancer Institute (NCI) at 3 sites 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 44 inclusion and 0 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 18 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 of MS-275 in combination with 5-azacitidine, assessed using Common Toxicity Criteria version 3.0 (time frame: 4 weeks). 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 NCT00101179, which also lists 3 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 18 Oct 2019.

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