A Pilot Study of the Safety and Activity of Escalating Doses of ON 01910.Na in Patients With Relapsed Mantle Cell Lymphoma, Multiple Myeloma, Chronic Lymphocytic Leukemia, and Related Lymphoid Malignancies

• Status: Completed
• Trial end date: 2012-10-19
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and other lymphoid malignancies are all incurable lymphoid malignancies that mainly affect persons in their late 60s and early 70s. Conventional chemotherapy can achieve high rates of clinical response, but relapse following these responses is almost universal. Patients with lymphoid malignancies relapse because their tumor cells become resistant to chemotherapy; therefore, new types of drugs are needed for better treatment responses.

• The investigational drug ON 01910.Na has been shown to be active against MCL and CLL cells, but further research is needed to determine the most safe and effective dose for this drug.

Objectives:

• To determine the maximum tolerated dose (the highest dose that does not cause unacceptable side effects) of ON 01910.Na in patients with cancers of the lymphoid cells.

• To study the effects that ON 01910.Na has on cancers of the lymphoid cells.

Eligibility:

• Patients 18 years of age and older who have been diagnosed with cancer of the lymphoid cells, and who have not been able to take or have not benefitted from existing treatment options.

Design:

• Evaluations before the treatment period:

• Full medical history and physical examination, and pregnancy test for women.

• Blood and urine tests.

• Disease evaluation with computerized tomography (CT) scan, magnetic resonance imaging (MRI), electrocardiogram; bone marrow and lymph node biopsies; and skeletal x-rays, if clinically indicated.

• Treatment with ON 01910.Na:

• Different research subjects will receive increasing doses of ON 01910.Na to determine which dose is considered safe.

• To reduce the risk of one rare serious side effect of treatment for myeloid malignancies, patients will take allopurinol 12 hours before and 7 days after each drug infusion, one 300 mg pill each day.

• Cycles 1 2: Patients will be admitted to the clinical center for 2 days at the beginning of each cycle. Each cycle involves intravenous infusion of ON 01910.Na continuously for a period of 48 hours, followed by 12 days of observation. Researchers will try to maintain the schedule of 2 days of infusion every 14 days, but the interval between doses may be extended if patients experience delayed recovery blood counts.

• Cycles 3 4: Patients who are doing well and choose to continue may receive an additional two cycles (2 days of inpatient infusion followed by 12 days of outpatient observation). At the end of cycle 4, researchers will determine if the disease is responding to therapy. Patients who experience side effects may continue to take ON 01910.Na at a lower dose or may stop receiving the drug.

• Patients who respond well to four cycles of ON 01910.Na may be eligible for additional cycles of ON 01910.Na.

• Patients who need to start another medication to treat their disease will stop taking ON 01910.Na, and the researchers will perform a final study visit 2 weeks after the last dose of ON 01910.Na. After that, participation in the study will be complete.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: ON 01910

Criteria

• INCLUSION CRITERIA:

1. Histologically documented or cytologically confirmed diagnosis of Mantle Cell Lymphoma (MCL) and refractory to, or relapsed after, greater than or equal to 1 prior lines of antineoplastic therapy (including an anthracycline or mitoxantrone and rituximab, each in one or more lines).

OR

Histologically documented or cytologically confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), or Prolymphocytic Lymphoma (PLL) and refractory to, or relapsed after, greater than or equal to 1 prior lines of antineoplastic therapy (including either a nucleoside analogue or an alkylating agent or a combination thereof. Must have relapsed after, failed or opted not to receive rituximab or alemtuzumab. Not a candidate for or opted not to participate in bone marrow transplantation.

OR

Histologically documented or cytologically confirmed diagnosis of Multiple Myeloma (MM) and refractory to, or relapsed after greater than or equal to 2 prior lines of antineoplastic therapy including both bortezomib and an immunomodulatory (IMiD) agent such as lenalidomide or thalidomide.

OR

Histologically documented or cytologically confirmed diagnosis of Waldenstrom s macroglobulinemia (WM) or Hairy Cell Leukemia (HCL) and refractory to, or relapsed after greater than or equal to 1 line of antineoplastic therapy.

2. Measurable disease (defined as two dimensional disease on imaging or quantifiable leukemic disease or monoclonal paraproteins).

3. Failed to respond to, relapsed following, not eligible for, or opted not to participate in other standard of care treatment options.

4. Age greater than or equal to 18 and less than or equal to 99.

EXCLUSION CRITERIA:

1. Less than 4 weeks since having received any other treatments directed toward their malignancy (standard or investigational). Steroids permissible up to 2 weeks prior to enrollment.

2. Malignant disease other than MCL, CLL/SLL, PLL, WM, HCL or MM requiring treatment with cytotoxic therapy.

3. Active infection not adequately responding to appropriate therapy.

4. HIV positive patients and taking anti-retroviral therapy.

5. Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient s ability to tolerate protocol therapy.

6. Symptomatic congestive heart failure, unstable angina pectoris, history of life threatening cardiac arrhythmia, myocardial infarction within 6 months or new conduction abnormalities by EKG. Patients with symptoms of coronary artery disease or EKG abnormalities must be evaluated and cleared by cardiology prior to enrollment.

7. Uncontrolled hypertension (defined as systolic pressure greater than or equal to 160 and/or diastolic pressure greater than or equal to 110).

8. New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures.

9. ECOG performance status 3 or 4.

10. Life expectancy less than 3 months.

11. Absolute neutrophil count (ANC) less than 500.

12. Platelet count less than 25,000 micro/L, unless responsive to platelet transfusion so that count can be maintained greater than 10,000 micro/L.

13. Total bilirubin greater than or equal to 1.5 mg/dL not related to hemolysis or Gilbert s disease, ALT or AST greater than or equal to 2 times ULN.

14. Serum creatinine greater than 1.5 times ULN or a calculated creatinine clearance of less than 40 mL/min/1.73 m(2).

15. Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of less than 134 meq/L).

16. Current pregnancy, unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential or currently breastfeeding.

17. Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol.

18. Major surgery within 3 weeks of ON 01910.Na treatment initiation

19. Psychiatric illness/social situations that would limit the patient s ability to tolerate and/or comply with study requirements.

20. Unable to understand the investigational nature of the study or give informed consent.