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Adult Acute Lymphoblastic Leukemia in RemissionPhase 2NCT00462605

MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

A Phase 2 study testing entinostat and sargramostim in people with Adult Acute Lymphoblastic Leukemia in Remission and Adult Acute Megakaryoblastic Leukemia (M7), 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 II trial is studying how well giving MS-275 together with GM-CSF works in treating patients with myelodysplastic syndrome and/or relapsed or refractory acute myeloid leukemia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
entinostat and sargramostim
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
Apr 2007to Mar 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 diseases by bone marrow aspiration and/or biopsy:
  • Myelodysplastic syndromes (MDS) meeting the following criteria:
  • Must have 1 of the following subtypes:
  • Refractory anemia (RA) (no RA with 5q-syndrome),
  • RA with ringed sideroblasts or
  • Refractory cytopenia with multilineage dysplasia
Show all 48Show fewer
  • Myelodysplastic syndromes (MDS) meeting the following criteria:
  • Must have 1 of the following subtypes:
  • Refractory cytopenia with multilineage dysplasia and ringed sideroblasts,
  • RA with excess blasts (RAEB)-1, RAEB-2,
  • Myelodysplastic syndromes, unclassified or
  • Chronic myelomonocytic leukemia
  • International Prognostic Scoring System score of intermediate-2 or high-risk
  • Acute myeloid leukemia (AML) meeting 1 of the following criteria:
  • Relapsed or refractory AML, including any of the following subtypes:
  • * AML with recurrent cytogenetic abnormalities (i.e., AML with 11q23 [MLL] abnormalities)
  • AML with multilineage dysplasia
  • AML that is therapy-related
  • AML, not otherwise categorized (M0 [minimally differentiated], M1 [without maturation], M2 [with maturation], M4 [myelomonocytic leukemia], M5 [monoblastic/monocytic leukemia], M6 [erythroid leukemia], and M7 [megakaryoblastic leukemia])
  • Untreated AML
  • Newly diagnosed patients are eligible provided they do not qualify for potentially curative intensive chemotherapeutic regimens
  • Acute lymphocytic leukemia (ALL) meeting 1 of the following criteria:
  • Relapsed or refractory ALL
  • Patients with any measurable residual disease are eligible, including cytogenetic abnormalities
  • Untreated ALL
  • Newly diagnosed patients are eligible provided they do not qualify for potentially curative intensive chemotherapeutic regimens, including any of the following:
  • Patients who have refused chemotherapy for untreated ALL
  • Patients who are deemed to be poor candidates medically for ALL induction chemotherapy
  • Relatively stable bone marrow function for > 7 days prior to study entry
  • WBC count that has not doubled within the past 7 days
  • WBC =<10,000/mm³
  • No uncontrolled peripheral leukemia (i.e., blast count > 30,000/mm³)
  • No active CNS disease
  • Lumbar puncture with negative cytology required for patients with clinical symptoms of active CNS disease
  • Not a candidate for a potentially curative allogeneic stem cell transplantation OR considered a poor candidate for such a procedure due to age, medical comorbidities, or lack of a suitable donor
  • Hemoglobin >= 8 g/dL (transfusions allowed)
  • Creatinine =< 2.0 mg/dL
  • Bilirubin =< 1.6 mg/dL (unless secondary to hemolysis)
  • AST or ALT =< 3 times upper limit of normal (unless disease-related)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No untreated or progressive infections
  • No history of intolerance to sargramostim (GM-CSF)
  • Recovered from all treatment-related toxicities
  • More than 2 weeks since prior therapy for AML, ALL, or MDS, including chemotherapy, hematopoietic growth factors, or biologic therapy such as monoclonal antibodies
  • Concurrent hydroxyurea allowed during course 1 for control of leukocytosis if WBC > 30,000/mm³
  • ECOG performance status 0-2

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins University

    Baltimore, Maryland, 21287-8936

Other trials in United States

About this study

Official title: A Phase II Study of and Oral Histone Deacytylase Inhibitor, MS-275 (NSC 706995), in Combination With Sargramostim (GM-CSF, Berlex, Inc.) Treating Relapsed and Refractory Myeloid Malignancies

This phase II trial is studying how well giving MS-275 together with GM-CSF works in treating patients with myelodysplastic syndrome and/or relapsed or refractory acute myeloid leukemia. MS-275 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving MS-275 together with GM-CSF may be an effective treatment for myelodysplastic syndrome and acute myeloid leukemia

Read the detailed description

PRIMARY OBJECTIVE:

  1. Determine clinical response in patients with myelodysplastic syndromes and/or relapsed or refractory acute myeloid leukemia or acute lymphocytic leukemia treated with MS-275 in combination with sargramostim (GM-CSF).

SECONDARY OBJECTIVES:

  1. Determine the clinical activity of this regimen, in terms of changes in peripheral blood counts and changes in individual patient transfusion requirements, in these patients.

II. Determine the biologic activity of this regimen, in terms of changes in the peripheral blood and bone marrow phenotype (i.e., induction of markers of myeloid differentiation or lymphoid differentiation) and changes in detectable cytogenetic abnormalities in the blood and marrow compartments, in these patients.

III. Determine the toxicity profile of this regimen in these patients.

OUTLINE:

Patients receive oral MS-275 on days 1, 8, 15, and 22. Patients also receive sargramostim (GM-CSF) subcutaneously once daily on days 1-42 in courses 3 and 5 and on days 1-35 in courses 1, 2, 4, and 6. Treatment repeats every 6 weeks for 2-6 courses in the absence of disease progression or unacceptable toxicity.

After completion of 2 courses of study therapy, patients who achieve a complete or partial response may receive an additional 4 courses. Patients who maintain stable disease for more than 2 months after completion of 6 courses of study therapy may receive an additional 6 courses at the time of disease progression, provided they meet original eligibility criteria.

Patients undergo blood and bone marrow (BM) collection at baseline and periodically during study for biologic correlative studies. Peripheral blood and bone marrow samples are assessed for changes in progenitor phenotype and clonogenic growth by flow cytometry and for changes in cytogenetics (i.e., malignant:nonmalignant cell ratio in BM CD34-positive cells, peripheral blood monocytes, peripheral blood neutrophils, and bone marrow and peripheral blood lymphoblasts) by FISH. Terminal differentiation of CD34-positive progenitor cells is studied in vitro in long-term cultures.

After completion of study therapy, patients are followed periodically for up to 2 years.

Being tested
entinostat, sargramostim
Medical subject headings
Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute, Leukemia, Myelomonocytic, Chronic, Myeloproliferative Disorders

What participants receive

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

  • entinostatDrug

    Also called HDAC inhibitor SNDX-275, SNDX-275

    Given PO

  • sargramostimDrug

    Also called GM-CSF, Leukine, Prokine

    Given SC

Study groups in NCT00462605
Study groupRoleWhat they receive
Arm IExperimentalPatients receive oral MS-275 on days 1, 8, 15, and 22. Patients also receive sargramostim (GM-CSF) subcutaneously once daily on days 1-42 in courses 3 and 5 and on days 1-35 in courses 1, 2, 4, and 6. Treatment repeats every 6 weeks for 2-6 courses in the absence of disease progression or unacceptable toxicity. After completion of 2 courses of study therapy, patients who achieve a complete or partial response may receive an additional 4 courses. Patients who maintain stable disease for more than 2 months after completion of 6 courses of study therapy may receive an additional 6 courses at the time of disease progression, provided they meet original eligibility criteria.
Receives: Drug: entinostat; Drug: sargramostim

What is being measured

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

  1. Response (Complete and Partial Response) in Patients With Myeloid Disorders

    Response to treatment was assessed after two cycles, according to International Working Group (IWG) criteria. Cytogenetic responses were monitored in patients with abnormalities at baseline.

    Measured: Up to 2 years

Secondary outcomes (4)

  1. Clinical Activity Assessed by Change in Peripheral Blood Counts

    Measured: Baseline and after 2 cycles

  2. Clinical Activity Assessed by Change in Transfusion Requirements

    Measured: Baseline and after 2 cycles

  3. Changes in Detectable Chromosomal Abnormalities Measured by Fluorescent in Situ Hybridization (FISH)

    Measured: Baseline and 6, 12, 24, and 36 weeks

  4. Change in the Percentage of Cells With Normal and Abnormal Myeloid Phenotype Measured by Flow Cytometry

    Measured: Baseline and 6, 12, 24, and 36 weeks

Timeline

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

  1. First posted19 Apr 2007 (estimated)
  2. Study startApr 2007
  3. Primary completionMar 2011
  4. Study completionMar 2011

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00462605
Sponsor's protocol ID
NCI-2009-00195
Other IDs
J06114, U01CA070095
Status last verified
Jun 2017
First submitted
18 Apr 2007
Last updated
18 Jul 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing entinostat and sargramostim in people with Adult Acute Lymphoblastic Leukemia in Remission and Adult Acute Megakaryoblastic Leukemia (M7), 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?

The sponsor lists 48 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 Jul 2017. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Response (Complete and Partial Response) in Patients With Myeloid Disorders (time frame: Up to 2 years). 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 NCT00462605.

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 Jul 2017.

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