Official Title: “SHP2 as a Therapeutic Target For Myelodysplastic Syndrome: Phase I/II Trial of Sodium Stibogluconate in Myelodysplastic Syndrome”

RATIONALE: Sodium stibogluconate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects of sodium stibogluconate and to see how well it works in treating patients with myelodysplastic syndromes.

Study Type: Interventional

Study Design: Treatment, Open Label

Study Primary Completion Date: August 2012

OBJECTIVES: - To determine the effect of sodium stibogluconate on clinical parameters (e.g., cytopenias, bone marrow dysplasia, percent of myeloid blasts, transfusion frequency, incidence of infection and phagocyte function at baseline and during treatment, and serum Sb levels as an early indication of toxicity) in patients with myelodysplastic syndromes. - To determine the effect of sodium stibogluconate on hematopoiesis (e.g., cytokine hypersensitivity, apoptosis resistance, and altered expression of key HoxA10 and ICSBP target genes in the bone marrow at baseline and during treatment) in these patients.

OUTLINE: Patients receive sodium stibogluconate IV over 30 minutes on days 1-5 and 15-19.

Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who respond to treatment may continue therapy until disease progression.

Patients undergo bone marrow aspiration, biopsy, and peripheral blood sample collection periodically for correlative laboratory studies.

After completion of study treatment, patients are followed up at 8 weeks.

Intervention(s) in this Clinical Trial

• Drug: sodium stibogluconate

Primary Measures

• Hematological parameters (e.g., SHP1/2 inhibition, cytokine hypersensitivity, apoptosis resistance, differentiation block, phagocyte function, and serum Sb levels)
  • Safety Issue?: No
• Correlation of SHP1/2 inhibition with each hematological parameter
  • Safety Issue?: No
• Clinical response (complete response, partial response, hematologic improvement, and disease progression)
  • Safety Issue?: No
• Time to progression to acute myeloid leukemia
  • Safety Issue?: No
• Toxicity (hematologic and non-hematologic)
  • Safety Issue?: Yes

DISEASE CHARACTERISTICS:

• Documented myelodysplastic syndromes (MDS), including therapy-related MDS
• Bone marrow evidence of MDS must include the following:
• Dysplasia of one or more lineages
• No more than 10% myeloid blasts
• Cytopenias of at least one lineage as evidenced by anemia (hemoglobin <
• 12.0 g/dL), granulocytopenia (granulocyte count < 1,500/mm³), or thrombocytopenia (platelet count < 100,000/mm³)
• International Prognostic Scoring System (IPSS) score of low, intermediate-1, or intermediate-2
• IPSS score of high allowed provided there are ≤ 10% blasts
• Meets 1 of the following criteria:
• Refractory to prior azacitidine or decitabine
• Did not tolerate treatment with azacitidine or decitabine due to cytopenias or other side effects
• Not a candidate for azacitidine or decitabine due to cytopenias or other medical conditions that would contraindicate nucleoside analogues
• Refused treatment with azacitidine or decitabine

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 16 weeks
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• SGOT and SGPT ≤ 2 times ULN
• Alkaline phosphatase ≤ 2 times ULN
• Amylase ≤ 2 times ULN
• Lipase ≤ 2 times ULN
• BUN ≤ 2 times ULN
• Creatinine ≤ 2 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No B12 deficiency, folate deficiency, or pyridoxine responsive anemia as confirmed by relevant laboratory testing
• No prolongation of QTc or ventricular ectopic beats on EKG
• No evidence of cardiac disease, including any of the following:
• Symptomatic coronary atherosclerotic heart disease
• Prolonged QT syndrome
• Prior ventricular tachycardia
• No active infection AND afebrile
• Patients completing antibiotics from a recent infection are eligible provided they are afebrile
• Febrile from blood product transfusion allowed provided there is an explanatory statement in the chart

PRIOR CONCURRENT THERAPY:

• More than 21 days since prior azacitidine or decitabine
• More than 21 days since other prior treatment for MDS (e.g., thalidomide, valproic acid, or other agents as part of a clinical trial)
• Prior cytokines (e.g., erythropoietin, G-CSF, and GM-CSF) allowed
• Prior chemotherapy and/or radiotherapy for solid tumors or lymphoma allowed provided there is no evidence of active disease from the prior malignancy
• No prior treatment for leukemia (e.g., acute myeloid leukemia, chronic myelogenous leukemia, acute lymphocytic leukemia, or chronic lymphocytic leukemia)
• No concurrent cytokines
• No concurrent antileukemic treatment, including bone marrow transplantation and radiotherapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Robert H. Lurie Cancer Center

Overall Clinical Trial Officials and Contacts

Elizabeth A. Eklund, MD Principal Investigator Robert H. Lurie Cancer Center  

Information obtained from ClinicalTrials.gov on February 04, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01009502

Study ID Number: CDR0000651241

ClinicalTrials.gov Identifier: NCT01009502

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database