Safety of ON 01910.Na in Patients With Myelodysplasia

NCT00533416 | Completed Phase 1

• 2 other identifiers: 07022507-H-0225
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myelodysplastic Syndrome (MDS)

Keywords

Myelodyplastic Syndrome (MDS); Selective Mitotic Inhibitor; Targeted Therapy; Myelodysplastic Syndrome; MDS

Outcome Measures

Primary Outcomes (1)

• The toxicity profile at each dose level.

Secondary Outcomes (1)

• Plasma pharmacokinetics, pharmacodynamics, and biological effects of hematologic improvement at each dose level.

Interventions

ON 01910 Na DRUG

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented or cytologically confirmed diagnosis of MDS with WHO classification of RAEB-1 or 2 or Intermediate to High IPSS risk group.
• Refractory acute myelogenous leukemia (AML) with trisomy 8
• Anemia requiring transfusion support with at least one unit of packed red blood cells per month for greater than or equal to 2 months
• Anemia (hemoglobin less than 9 or a reticulocyte count less than 60,000/microL)
• thrombocytopenia (platelet count less than 50,000/microL)
• neutropenia (absolute neutrophil count less than 500/microL).
• Failed to respond to, relapsed following, or opted not to participate in bone marrow transplantation or other standard of care treatment options.
• ECOG Performance Status of 0, 1, or 2.
• 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.
• Ages 18-85.

You may not qualify if:

• Active infection not adequately responding to appropriate therapy.
• Hypoplastic MDS (cellularity less than 10 percent) or an absolute neutrophil count of less than 200 cells/microL.
• Active malignant disease (excluding non-melanoma skin carcinoma) other than AML.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• An expected survival, in the opinion of the investigator that would not permit a sufficient observation period for evaluating ON 01910.Na.
• HIV positive patients.
• Total bilirubin greater than 1.5 mg/dL not related to hemolysis or Gilbert s disease.
• Serum creatinine greater than 1.5 mg/dL, or a calculated creatinine clearance of less than 60 mL/min/1.73 m(2).
• Ascites requiring active medical management including paracentesis, peripheral bilateral edema, hyponatremia (serum sodium less than 134 meq/L.
• Currently receiving any other investigational agents or concurrent chemotherapy, radiotherapy, or immunotherapy.
• 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.
• Psychiatric illness/social situations that would limit the patient s ability to tolerate and/or comply with study requirements.
• Unable to understand the investigational nature of the study or give informed consent.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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. doi: 10.1016/s0037-1963(00)90027-1.

  PMID: 10676908 BACKGROUND

• 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.

  PMID: 8464227 BACKGROUND

• 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. doi: 10.1182/blood.v98.8.2326.

  PMID: 11588026 BACKGROUND

• Olnes MJ, Shenoy A, Weinstein B, Pfannes L, Loeliger K, Tucker Z, Tian X, Kwak M, Wilhelm F, Yong AS, Maric I, Maniar M, Scheinberg P, Groopman J, Young NS, Sloand EM. Directed therapy for patients with myelodysplastic syndromes (MDS) by suppression of cyclin D1 with ON 01910.Na. Leuk Res. 2012 Aug;36(8):982-9. doi: 10.1016/j.leukres.2012.04.002. Epub 2012 Apr 21.

  PMID: 22524974 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

ON 01910

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Neal S Young, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2007
• First Posted: September 21, 2007
• Study Start: September 14, 2007
• Primary Completion: June 4, 2012
• Study Completion: June 4, 2012
• Last Updated: December 17, 2019

Record last verified: 2016-04-27

Locations

US (1)