LeukemiaPhase 1NCT00015925
MS-275 in Treating Patients With Hematologic Cancer
A Phase 1 study testing entinostat in people with Leukemia and Multiple Myeloma and Plasma Cell Neoplasm, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of MS-275 in treating patients who have hematologic cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- What is being tested?
- entinostat
- How many people
- Not given
- Where
- 2 sitesUnited States
- Study dates
- Feb 2001to not given
- 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:
- One of the following histologically confirmed diagnoses:
- Acute myeloid leukemia (AML)
- Newly diagnosed de novo AML in patients over 60 years old with the following poor-risk features:
- Antecedent hematologic disorder
- Complex karyotype or other adverse cytogenetics
- Stem cell immunophenotype
- AML arising from myelodysplastic syndromes (MDS)
- Secondary AML
- Relapsed or refractory AML, including primary induction failure
- MDS
- Poor-risk, defined as the following:
- International Performance Score at least 1.5
- More than 10% marrow blasts
- Cytopenias in at least 2 lineages
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation
- Chronic myelomonocytic leukemia
- Acute lymphoblastic leukemia (ALL)
- Newly diagnosed de novo ALL in patients over 60 years old with the following poor-risk features:
- Complex karyotype or other adverse cytogenetics
- Mixed lineage immunophenotype
- Relapsed or refractory ALL, including primary induction failure
- Chronic myelogenous leukemia (CML)
- CML in accelerated phase or blast crisis
- Interferon-refractory CML in chronic phase
- Multiple myeloma (MM)
- Relapsed or refractory, including prior autologous stem cell transplantation
- Acute promyelocytic leukemia
- Prior treatment with tretinoin
- Ineligible for arsenic trioxide
- No evidence of active coagulopathy
- Low-risk for developing clinically significant coagulopathy during study
- Low tumor burden by marrow aspiration at time of relapse
- No prior coagulation-related sequelae (deep vein thrombosis, pulmonary embolism, or CNS thrombosis or bleed)
- Failure after primary induction therapy or relapse after complete remission allowed if patient received no more than 3 courses of prior induction/reinduction therapy
- Not eligible for curative stem cell transplantation
- No hyperleukocytosis with at least 50,000/mm^3 leukemic blasts
- No active CNS leukemia
- No plasma cell leukemia
- No amyloidosis resulting in major organ dysfunction
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
- No disseminated intravascular coagulation
- No hyperviscosity
Hepatic:
- AST/ALT no greater than 2 times normal
- Alkaline phosphatase no greater than 2 times normal
- Bilirubin no greater than 1.5 times normal
Renal:
- Creatinine no greater than 1.5 times normal
- No uncorrected hypercalcemia
Cardiovascular:
- See Disease Characteristics
- LVEF at least 45% by MUGA or echocardiogram
- No intrinsic impaired cardiac function, including any of the following:
- Myocardial infarction within the past 3 months
- Prior severe coronary artery disease
- Cardiomyopathy
- Congestive heart failure
Other:
- No active uncontrolled infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
- At least 1 week since prior growth factors (epoetin alfa, filgrastim [G-CSF], sargramostim [GM-CSF], interleukin [IL]-3, or IL-11)
- At least 4 weeks since prior autologous stem cell transplantation
- No prior allogeneic stem cell transplantation
- No concurrent immunotherapy
Chemotherapy:
- See Disease Characteristics
- At least 3 weeks since prior chemotherapy and recovered
- At least 24 hours since prior hydroxyurea or mercaptopurine for prevention of leukostasis
- No concurrent chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- At least 2 weeks since prior emergency radiotherapy to large soft tissue or lytic bony lesions for MM
- No concurrent radiotherapy
Surgery:
- Not specified
Other:
- At least 24 hours since other prior noncytotoxic agents for prevention of leukostasis
- No other concurrent antitumor therapy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, 21201
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
About this study
Official title: Phase I Clinical-Labratory Study of the Histone Deacetylase (HDA) Inhibitor MS-275 in Adults With Refractory and Relapsed Hematologic Malignancies
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: Phase I trial to study the effectiveness of MS-275 in treating patients who have hematologic cancer.
Read the detailed description
OBJECTIVES:
- Determine the toxic effects and pharmacokinetics of MS-275 in patients with poor-risk hematologic malignancy.
- Determine whether this drug induces changes in hematologic differentiation, in terms of changes in morphology, cell surface marker expression, and acetylation status, in these patients.
- Determine whether this drug induces clinical response in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oral MS-275 on days 1, 8, 15, and 22. Courses repeat every 6 weeks 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. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: Approximately 25-30 patients will be accrued for this study.
- Conditions
- Leukemia, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Being tested
- entinostat
- Keywords
- refractory multiple myeloma, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, untreated adult acute lymphoblastic leukemia, untreated adult acute myeloid leukemia, adult acute promyelocytic leukemia (M3), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, atypical chronic myeloid leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22)
- Medical subject headings
- Leukemia, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
entinostatDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startFeb 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Judith E. Karp, MD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00015925
- Sponsor's protocol ID
- CDR0000068574, J0253
- Other IDs
- U01CA069854, P30CA006973, JHOC-J0253, MSGCC-0050, NCI-2791
- Status last verified
- Mar 2010
- First submitted
- 6 May 2001
- Last updated
- 10 Mar 2010
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical-Labratory Study of the Histone Deacetylase (HDA) Inhibitor MS-275 in Adults With Refractory and Relapsed Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00015925
- Acronym / sponsor ID
- CDR0000068574, J0253
- Conditions
- Leukemia, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Keywords
- refractory multiple myeloma, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, untreated adult acute lymphoblastic leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2001
- First posted
- 27 Jan 2003 (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.
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: Phase I trial to study the effectiveness of MS-275 in treating patients who have hematologic cancer.
Detailed description
OBJECTIVES:
- Determine the toxic effects and pharmacokinetics of MS-275 in patients with poor-risk hematologic malignancy.
- Determine whether this drug induces changes in hematologic differentiation, in terms of changes in morphology, cell surface marker expression, and acetylation status, in these patients.
- Determine whether this drug induces clinical response in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oral MS-275 on days 1, 8, 15, and 22. Courses repeat every 6 weeks 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. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: Approximately 25-30 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
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 |
|---|---|---|
| entinostat | Drug | – |
Primary outcome
Not reported in the source record.
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 10 Mar 2010.
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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.
Judith E. Karp, MD study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing entinostat in people with Leukemia and Multiple Myeloma and Plasma Cell Neoplasm, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 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?
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 10 Mar 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
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 10 Mar 2010.