A Phase II Study of MS-275, in Combination With GM-CSF Treating Relapsed and Refractory Myeloid Malignancies

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00466115
• Other study ID #: NCI Protocol : #7605
• Status: Not yet recruiting
• Phase: Phase 2
• First received: April 25, 2007
• Last updated: April 25, 2007
• Start date: April 2007
• Est. completion date: April 2007

Study information

• Verified date: April 2007
• Source: Johns Hopkins University
• Contact: B.Douglas Smith, MD
• Phone: (410) 287-2935
• Email: smithdo[@]jhmi.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This research is being done to see if the combination of sargramostim and MS-275 will help to improve the bone marrow function of people with myelodysplastic syndrome (MDS) or acute myeloid leukemia(AML).

It will also determine the side effects of this combination.

Description:

MDS is an abnormality of the bone marrow and blood cells that may develop into cancer.

AML is a cancer of the bone marrow and blood cells. Both result in problems making normal blood cells. The cells in the bone marrow do not undergo the normal expected patterns of growth or maturation that is called “differentiation.” Because of this, they do not work very well. People with these problems often need blood transfusions and are at high risk for infections and bleeding.

Treatment options for MDS and AML are often limited due to their side effects. We hope to develop combinations of drugs that will help the bone marrow function better without many of the side effects of traditional chemotherapy treatments.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

In general, patients with MDS and relapsed or refractory AML, who are not eligible for a potentially curative myeloablative allogeneic stem cell transplant or who are considered poor candidates for such a procedure due to age, medical co-morbidities, or lack of a suitable donor, will be considered for participation in the proposed trial.

Disease Specific Inclusion Criteria:

• MDS

• Relapsed AML

• Untreated AML

Additional Criteria:

1. Age > 18.

2. JHOC confirmed and documented diagnosis of either AML or MDS within 12 weeks of trial enrollment. Patients with MDS are restricted to those with IPSS of INT-2 or high risk.

3. Patients must have relatively stable bone marrow function for more than seven days prior to enrollment on the study. WBC count doubling within seven days of enrollment or WBC greater than 10 x 103/dL would indicate unstable bone marrow function.

4. ECOG performance status of 0, 1, 2.

5. Patient or caregiver must be willing to perform subcutaneous injection.

6. Patients must have the following end organ function:

• Serum creatinine < 2.0 mg/dL

• Total serum bilirubin < 1.6 mg/dL, unless secondary to hemolysis.

• SGOT/SGPT each < 3 times the upper limit of normal unless disease related

• Hemoglobin should be at least 8 gm/dL at the time of protocol entry. Patients may receive transfusions to achieve this level.

7. Patients must not have received treatment for their myeloid disorder within 2 weeks of beginning the trial. Treatments include the use of chemotherapy, hematopoietic growth factors, and biologic therapy such as monoclonal antibodies. The exception is the use of hydroxyurea for patients with WBC > 30 x 103/µL. This duration of time appears adequate for wash out due to the relatively short-acting nature of most anti-leukemia agents.

8. Patients must have recovered from all toxicities (to grade 0 or 1) associated with previous treatment.

9. Patients must not have any clinical symptoms of active CNS disease. If CNS disease is suspected, patient must have LP with negative cytology.

10. All women of potential child bearing must have negative urine or serum B-HCG prior to enrollment.

11. All women of potential child bearing must agree to use adequate birth control throughout the trial period. All men must agree to use barrier contraceptive throughout the trial period.

12. Patients must be able to provide informed consent and to return to clinic for adequate follow up as required by the protocol.

Exclusion Criteria:

1. Diagnosis of RA with 5q- syndrome

2. Peripheral leukemia with blast count > 30 x 103/dL, uncontrolled with hydroxyurea.

3. Age < 18

4. ECOG performance status > 3

5. Patients with untreated or progressive infections

6. Patients with active CNS disease

7. Patients with a previous history of intolerance to GM-CSF

8. Pregnant or lactating women

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• MS-275

• GM-CSF

Locations

Country	Name	City	State
United States	Johns Hopkins University - Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All patient initiated on combination therapy will be evaluable for toxicity. Efficacy will be evaluated following two cycles of therapy.