Patients with myelodysplastic syndrome (MDS) present with low red blood cells, white blood cells and platelets, alone or in combination. The only definitive treatment is stem cell transplantation. Unfortunately, treatment-related mortality precludes the application of this procedure for most patients older than 60 years and those lacking a suitable matched sibling donor. A proportion of patients have been shown to respond to a wide variety of immunosuppressive agents, including cyclosporine (CSA) and antithymocyte globulin (ATG). However, nonresponse and relapse continue to be problematic. Therefore, most patients with MDS receive supportive treatment with transfusions and growth factors, such as erythropoietin (EPO) and G-CSF, to improve blood counts. However, growth factors are not always effective in improving cytopenias and iron overload is an inevitable long-term complication of red blood cell transfusions.

Recently, Abkowitz et al described clinically significant improvement in anemia in 3 of 9 patients with Diamond-Blackfan anemia (DBA) using metoclopramide, an inexpensive, commonly used medication with rare side effects. We hypothesize that therapy with metoclopramide might also benefit patients with other causes of refractory anemia, such as individuals with anemia due to MDS. We therefore propose this Phase II multicenter clinical trial to evaluate metoclopramide in the treatment of anemia in patients with MDS.

Intervention	Phase
Drug: Metoclopramide	Phase II

Further Study Details: 

Expected Total Enrollment:  60

Patients with myelodysplastic syndrome (MDS) present with low red blood cells, white blood cells and platelets, alone or in combination. The only definitive treatment is stem cell transplantation. Unfortunately, treatment-related mortality precludes the application of this procedure for most patients older than 60 years and those lacking a suitable matched sibling donor. A proportion of patients have been shown to respond to a wide variety of immunosuppressive agents, including cyclosporine (CSA) and antithymocyte globulin (ATG). However, nonresponse and relapse continue to be problematic. Therefore, most patients with MDS receive supportive treatment with transfusions and growth factors, such as erythropoietin (EPO) and G-CSF, to improve blood counts. However, growth factors are not always effective in improving cytopenias and iron overload is an inevitable long-term complication of red blood cell transfusions.

Recently, Abkowitz et al described clinically significant improvement in anemia in 3 of 9 patients with Diamond-Blackfan anemia (DBA) using metoclopramide, an inexpensive, commonly used medication with rare side effects. We hypothesize that therapy with metoclopramide might also benefit patients with other causes of refractory anemia, such as individuals with anemia due to MDS. We therefore propose this Phase II multicenter clinical trial to evaluate metoclopramide in the treatment of anemia in patients with MDS.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:

1) MDS patients in IPSS risk group low or intermediate-1

OR

MDS patients in IPSS risk group intermediate-2 if greater than 60 years of age and not eligible for high intensity therapies, including intensive combination chemotherapy or hematopoietic cell transplant

2) Off all other treatments for MDS, except red blood cell transfusion support, for at least 4 weeks

3) Anemia as defined by hemoglobin less than11g/dL

4) Absolute reticulocyte count less than 31,700/uL (NIH) or less than 20,000/uL (Seattle), based on two baseline lab tests

5) Absolute neutrophil count greater than 200/uL

6) Platelet count greater than 10,000/uL.

7) Ages 18 to 72

8) ECOG performance status less than or equal to 2

9) Ability to understand the investigational nature of the protocol and provide informed consent.

EXCLUSION CRITERIA:

1) MDS patients in high IPSS risk group

2) Patients with secondary MDS

3) Previous history of dystonic reaction and/or anaphylactic reaction to metoclopramide

4) History of GI obstruction/perforation, pheochromocytoma, seizure disorders, creatinine clearance less than or equal to 50mL/min (estimated creatinine clearance = [weight (Kg) x (140-age) x (0.85 if female)]/[72 x (stable creatinine)], Parkinson''''s disease, breast cancer, clinically active depression, or hypertension due to pheochromocytoma

5) Current pregnancy (positive serum Beta-HCG if menstruating female), or unwilling to use a medically acceptable contraceptive or refrain from pregnancy if of childbearing potential

6) Concomitant drug therapy with high risks of extrapyramidal side effects (namely antipsychotic drugs including haloperidol, trifluoperazine, fluphenazine, thiothixene, perphenazine and pimozide)

7) Metoclopramide therapy 4 months prior to study enrollment

Please refer to this study by ClinicalTrials.gov identifier  NCT00120653

Maryland
      National Heart, Lung and Blood Institute (NHLBI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050201; 05-H-0201
Record last reviewed:  July 12, 2005
Last Updated:  July 20, 2005
Record first received:  July 16, 2005
ClinicalTrials.gov Identifier:  NCT00120653
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-26