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Sponsored by: |
National Heart, Lung, and Blood Institute (NHLBI) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00861510 |
Mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM) and the related lymphoid malignancies included in this protocol are all incurable lymphoid malignancies that mainly affect persons in their late 60s and early 70s. Conventional chemotherapy can be effective at achieving high rates of clinical response, but relapse following these responses is almost universal. Response rates in the relapsed setting are inferior due to acquired resistance of the tumor cells and new therapies with novel mechanisms of action are needed. Our aim in this study is to specifically address the needs of these patients for whom few effective treatments are available.
Patients with lymphoid malignancies relapse due to acquired resistance of tumor cells to chemotherapy agents and innovative targeted therapies which overcome these mechanisms of resistance are needed. One such investigational drug, ON 01910.Na, is a potent and selective inhibitor of the cell cycle and leads to reduction in cyclin D1 expression. In vitro, ON01910.Na shows activity against CLL and MCL cell lines with resultant cellular death. The overexpression of cyclin D1 in these related lymphoid malignancies provides a rationale for it use in selected patients with these conditions.
We therefore propose this non-randomized, pilot, dose-escalating Phase I study of ON 01910.Na in patients with MCL, CLL, MM and related lymphoid malignancies who have relapsed after or are refractory to standard therapy.
The primary objective is to determine the toxicity profile (including the maximum tolerated dose and recommended phase II dose) of ON 01910.Na when administered the first 2 days of a 2-week cycle in escalating doses (1200mg/m2/day x 2 days, 1500mg/m2/day x 2 days, 1800mg/m2/day x 2 days, and 2100mg/m2/day x 2 days ) in patients with MCL, CLL, MM and related lymphoid malignancies.
Secondary objectives include, the biological effects of ON 01910.Na (for example cyclin D1 expression) on cell-cycle pathways of cells obtained from blood, lymph nodes or bone marrow, the toxicity profile of ON 01910.Na with subsequent dosing after 2 cycles of therapy, early indications of biologic activity after 4 cycles of therapy, evaluation of the pharmacokinetics of ON 01910.Na at the RPTD level, and indications of biologic activity during extended access (after 4 cycles (day 56)).
The primary endpoint will be the toxicity profile at each dose level through day 28 (cycle 2 day 14)
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Condition | Intervention | Phase |
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Lymphoma, Mantle-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Hairy Cell Waldenstrom Macroglobulinemia Multiple Myeloma |
Drug: ON01910 Na |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study |
Official Title: | 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 |
Estimated Enrollment: | 39 |
Study Start Date: | March 2009 |
Mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM) and the related lymphoid malignancies included in this protocol are all incurable lymphoid malignancies that mainly affect persons in their late 60s and early 70s. Conventional chemotherapy can be effective at achieving high rates of clinical response, but relapse following these responses is almost universal. Response rates in the relapsed setting are inferior due to acquired resistance of the tumor cells and new therapies with novel mechanisms of action are needed. Our aim in this study is to specifically address the needs of these patients for whom few effective treatments are available.
Patients with lymphoid malignancies relapse due to acquired resistance of tumor cells to chemotherapy agents and innovative targeted therapies which overcome these mechanisms of resistance are needed. One such investigational drug, ON 01910.Na, is a potent and selective inhibitor of the cell cycle and leads to reduction in cyclin D1 expression. In vitro, ON01910.Na shows activity against CLL and MCL cell lines with resultant cellular death. The overexpression of cyclin D1 in these related lymphoid malignancies provides a rationale for it use in selected patients with these conditions.
We therefore propose this non-randomized, pilot, dose-escalating Phase I study of ON 01910.Na in patients with MCL, CLL, MM and related lymphoid malignancies who have relapsed after or are refractory to standard therapy.
The primary objective is to determine the toxicity profile (including the maximum tolerated dose and recommended phase II dose) of ON 01910.Na when administered the first 2 days of a 2-week cycle in escalating doses (1200mg/m2/day x 2 days, 1500mg/m2/day x 2 days, 1800mg/m2/day x 2 days, and 2100mg/m2/day x 2 days ) in patients with MCL, CLL, MM and related lymphoid malignancies.
Secondary objectives include, the biological effects of ON 01910.Na (for example cyclin D1 expression) on cell-cycle pathways of cells obtained from blood, lymph nodes or bone marrow, the toxicity profile of ON 01910.Na with subsequent dosing after 2 cycles of therapy, early indications of biologic activity after 4 cycles of therapy, evaluation of the pharmacokinetics of ON 01910.Na at the RPTD level, and indications of biologic activity during extended access (after 4 cycles (day 56)).
The primary endpoint will be the toxicity profile at each dose level through day 28 (cycle 2 day 14)
Secondary endpoints include the reduction in lymph nodes, quantification of circulating lymphoma cells, assessment of extranodal disease sites, and/or measurement of the malignant monoclonal proteins in the serum or urine after 4 cycles of therapy (day 56)
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA:
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 2 prior lines of antineoplastic therapy (including at least one nucleoside analogue and one alkylating agent or a combination thereof as well as rituximab, each in greater than or equal to 1 line). Must have relapsed after, failed or opted not to receive 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.
EXCLUSION CRITERIA:
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Study ID Numbers: | 090094, 09-H-0094 |
Study First Received: | March 12, 2009 |
Last Updated: | April 9, 2009 |
ClinicalTrials.gov Identifier: | NCT00861510 History of Changes |
Health Authority: | United States: Federal Government |
Small Lymphocytic Lymphoma (SLL) Prolymphocytic Lymphoma (PLL) Hairy Cell Leukemia (HCL) |
Leukemia, Lymphoid Blood Protein Disorders Lymphoma, Mantle-Cell Paraproteinemias Mantle Cell Lymphoma Hemostatic Disorders Leukemia Hemorrhagic Disorders Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, B-cell, Chronic Lymphoma Immunoproliferative Disorders Hematologic Diseases |
Blood Coagulation Disorders Hairy Cell Leukemia Vascular Diseases Multiple Myeloma Lymphatic Diseases Leukemia, Hairy Cell Waldenstrom Macroglobulinemia Chronic Lymphocytic Leukemia Lymphoproliferative Disorders Leukemia, B-Cell Lymphoma, Non-Hodgkin Neoplasms, Plasma Cell |
Leukemia, Lymphoid Immunoproliferative Disorders Neoplasms by Histologic Type Immune System Diseases Hematologic Diseases Blood Protein Disorders Lymphoma, Mantle-Cell Vascular Diseases Paraproteinemias Hemostatic Disorders Multiple Myeloma Lymphatic Diseases |
Leukemia Leukemia, Hairy Cell Waldenstrom Macroglobulinemia Neoplasms Hemorrhagic Disorders Leukemia, Lymphocytic, Chronic, B-Cell Cardiovascular Diseases Lymphoma, Non-Hodgkin Leukemia, B-Cell Lymphoproliferative Disorders Lymphoma Neoplasms, Plasma Cell |