Myelodysplastic Syndrome (MDS) Clinical Trial
Official title:
A Pilot Study of the Safety and Activity of Escalating Doses of ON 01910.Na in Patients With RAEB-1 AND RAEB-2 Myelodysplastic Syndrome (MDS) and AML With Trisomy 8
Verified date | April 27, 2016 |
Source | National Institutes of Health Clinical Center (CC) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This study will determine the highest dose of the experimental drug ON 01910.Na that can
safely be given to patients with the bone marrow disorder myelodysplasia (MDS) and patients
with refractory AML with trisomy 8. In this disease, the bone marrow can make some blood
cells, but very few of these cells are released into the blood for use in the body. ON
01910.Na is an experimental drug that inhibits a protein called cyclinD1that is important for
keeping MDS cells alive. In laboratory experiments, ON 01910.Na has acted against cyclinD1,
causing MDS cells to die. The study will also evaluate how the body handles ON 01910.Na, the
effect of the drug on MDS and AML and its side effects.
Patients 18 to 85 years old with MDS or AML who do not have a suitable sibling donor for a
marrow transplant or who are not willing to have a transplant may be eligible for this study.
Participants receive ON 01910.Na in 2-week treatment cycles, with 3 to 5 days of drug
infusion through a vein followed by 9 to 11 days of observation. To find the highest safe
dose of ON 01910.Na, the first person enrolled in the study is given the smallest study dose
of the drug for 3 days, followed 2 weeks later with a second dose for 3 days. If these doses
are found safe, the next two people receive the same dose. If these subjects do well, the
next group of patients receives the next higher dose level. The dose continues to be
increased in groups of 3 to 6 subjects until the fourth and highest dose level is reached.
Patients who do well on the treatment may receive an additional six cycles of ON 01910.Na (3
to 5 days of infusion once every other week for 12 weeks).
Before, during and after the treatment period, patients are periodically evaluated and
monitored with the following tests and procedures:
- Physical examination and review of medical and medication history.
- Blood and urine tests.
- Pregnancy test for women of childbearing age.
- Electrocardiogram (EKG) and chest X-ray.
- Bone marrow biopsy.
Status | Completed |
Enrollment | 14 |
Est. completion date | June 4, 2012 |
Est. primary completion date | June 4, 2012 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 85 Years |
Eligibility |
- All patients 18-85 years old with RAEB1 or RAEB 2 MDS or refractory AML with trisomy 8
who lack a suitable matched sibling marrow will be considered for enrollment. Patients
who have a suitable matched sibling donor will be referred for consideration of
allogeneic bone marrow transplantation. Patients not willing to undergo
transplantation or have relapsed following transplantation will be considered for
protocol participation. INCLUSION CRITERIA: 1. Histologically documented or cytologically confirmed diagnosis of MDS with WHO classification of RAEB-1 or 2 or Intermediate to High IPSS risk group. OR Refractory acute myelogenous leukemia (AML) with trisomy 8 2. Anemia requiring transfusion support with at least one unit of packed red blood cells per month for greater than or equal to 2 months OR Anemia (hemoglobin less than 9 or a reticulocyte count less than 60,000/microL) OR thrombocytopenia (platelet count less than 50,000/microL) OR neutropenia (absolute neutrophil count less than 500/microL). 3. Failed to respond to, relapsed following, or opted not to participate in bone marrow transplantation or other standard of care treatment options. 4. ECOG Performance Status of 0, 1, or 2. 5. Off all other treatments for MDS or AML (except filgrastim (G-CSF), erythropoietin, and transfusion support and related medications) for at least four weeks. Filgrastim (G-CSF) can be used before, during and after the protocol treatment for patients with documented neutropenia (less than 500/microL) as long as they meet the criteria for anemia and/or thrombocytopenia as stated above. Post transplant patients may continue to receive DLIs as needed. 6. Ages 18-85. EXCLUSION CRITERIA: 1. Active infection not adequately responding to appropriate therapy. 2. Hypoplastic MDS (cellularity less than 10 percent) or an absolute neutrophil count of less than 200 cells/microL. 3. Active malignant disease (excluding non-melanoma skin carcinoma) other than AML. 4. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. 5. An expected survival, in the opinion of the investigator that would not permit a sufficient observation period for evaluating ON 01910.Na. 6. HIV positive patients. 7. Total bilirubin greater than 1.5 mg/dL not related to hemolysis or Gilbert s disease. 8. Serum creatinine greater than 1.5 mg/dL, or a calculated creatinine clearance of less than 60 mL/min/1.73 m(2). 9. Ascites requiring active medical management including paracentesis, peripheral bilateral edema, hyponatremia (serum sodium less than 134 meq/L. 10. Currently receiving any other investigational agents or concurrent chemotherapy, radiotherapy, or immunotherapy. 11. Current pregnancy, unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential or currently breastfeeding. Pregnant and nursing women are excluded from this study. 12. Psychiatric illness/social situations that would limit the patient s ability to tolerate and/or comply with study requirements. 13. Unable to understand the investigational nature of the study or give informed consent. |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Heart, Lung, and Blood Institute (NHLBI) |
United States,
Barrett J, Saunthararajah Y, Molldrem J. Myelodysplastic syndrome and aplastic anemia: distinct entities or diseases linked by a common pathophysiology? Semin Hematol. 2000 Jan;37(1):15-29. Review. — View Citation
de Witte T, Suciu S, Verhoef G, Labar B, Archimbaud E, Aul C, Selleslag D, Ferrant A, Wijermans P, Mandelli F, Amadori S, Jehn U, Muus P, Boogaerts M, Zittoun R, Gratwohl A, Zwierzina H, Hagemeijer A, Willemze R. Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS. Blood. 2001 Oct 15;98(8):2326-31. Erratum in: Blood 2002 Mar 1;99(5):1535. — View Citation
Toyama K, Ohyashiki K, Yoshida Y, Abe T, Asano S, Hirai H, Hirashima K, Hotta T, Kuramoto A, Kuriya S, et al. Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan. Leukemia. 1993 Apr;7(4):499-508. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The toxicity profile at each dose level. | |||
Secondary | Plasma pharmacokinetics, pharmacodynamics, and biological effects of hematologic improvement at each dose level. |
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