p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Refractory/Relapsed Lymphoid Malignancies
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|ClinicalTrials.gov Identifier: NCT02846935|
Recruitment Status : Completed
First Posted : July 27, 2016
Last Update Posted : January 7, 2019
|Condition or disease||Intervention/treatment||Phase|
|T-cell Lymphoma Aggressive B-cell Lymphoma Non-Hodgkin's Lymphomas Indolent B-cell Lymphoma||Drug: Decitabine Drug: Tetrahydrouridine||Early Phase 1|
Primary objective: To determine the objective response rate to oral THU-Dec in patients with 3 separate biologic subsets of refractory/relapsed lymphoid malignancies:
- T-cell lymphoma,
- Aggressive B cell lymphoma,
- indolent B-cell lymphoma .
(i) To evaluate the toxicity of oral THU-Dec in these patients; (ii) To evaluate hypotheses regarding mechanisms of resistance and predictive biomarkers.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Refractory/Relapsed Lymphoid Malignancies|
|Actual Study Start Date :||April 25, 2017|
|Actual Primary Completion Date :||January 22, 2018|
|Actual Study Completion Date :||January 22, 2018|
Experimental: Decitabine + Tetrahydrouridine
oral THU dosed by weight, followed by oral decitabine dosed by weight for 60 minutes (± 10 minutes) after the THU, twice weekly on consecutive days.
Treatment on protocol monitoring continues for 52 weeks.
2-4 capsules depending on the weight of participant. Dec capsules are ingested ~60 minutes after THU capsules.
Other Name: DEC
2-4 capsules depending on the weight of participant. Oral THU capsules followed 60 minutes later by oral Dec capsules are ingested 2X/week on consecutive days.
Other Name: THU
- Objective Response by Revised Response Criteria for Malignant Lymphoma [ Time Frame: Up to 52 weeks ]
- Complete Response [ Time Frame: Up to 52 weeks ]Complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy
- Partial Response [ Time Frame: Up to 52 weeks ]
A > 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses. These nodes should be selected according to the following: (a) they should be clearly measurable in at least 2 perpendicular dimensions; (b) they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.
No increase in the size of other nodes, liver or spleen.
Bone marrow assessment is irrelevant for determination of a PR if the sample was positive prior to treatment. However, if positive, the cell type should be specified, e.g. large-cell lymphoma or small cleaved cell lymphoma.
No new sites of disease
- Stable Disease [ Time Frame: Up to 52 weeks ]
Failing to attain the criteria needed for a PR or CR, but not fulfilling those for progressive disease.
For FDG-avid lymphomas: FDG-PET/CT should be positive at prior sites of disease with no new areas of involvement on the post-treatment CT or FDG-PET/CT.
For variably FDG-avid lymphomas/FDG-avidity unknown: For patients without a pretreatment FDG-PET/CT scan or if the pre-treatment FDG-PET/CT was negative, there must be no change in the size of the previous lesions on the post-treatment CT scan.
- Progressive Disease [ Time Frame: Up to 52 weeks ]For determination of relapsed and progressive disease, lymph nodes should be considered abnormal if the long axis is more than 1.5 cm, regardless of the short axis. If a lymph node has a long axis of 1.1 to 1.5 cm, it should only be considered abnormal if the short axis is more than 1 cm. Lymph nodes < 1 x < 1 cm will not be considered as abnormal for relapse or progressive disease. Treatment decisions in patients with presumed refractory, relapsed or progressive disease should not be made solely on the basis of a single FDG-PET/CT scan without histologic confirmation.
- Duration of response [ Time Frame: Up to 52 weeks ]This is measured, only in responders, from the documented beginning of response (CR or PR) to the time of relapse.
- Disease-free survival [ Time Frame: Up to 52 weeks ]Survival is defined as the date of study entry to the date of death. Disease-free survival is measured from the time of occurrence of disease-free state (e.g. the adjuvant setting following surgery or radiation therapy) or attainment of a complete remission) to disease recurrence or death from lymphoma or acute toxicity of treatment. This definition may be complicated by deaths that occur during the follow-up period that are unrelated to the lymphoma and there is controversy as to whether such deaths should be considered as events or censored at the time of occurrence. Whereas it is often possible to identify those deaths related to the lymphoma, there is the potential for bias in the attribution of deaths.
- Disease-specific survival [ Time Frame: Up to 52 weeks ]Disease-specific survival (e.g., lymphoma-specific survival, cause-specific survival) is potentially subject to bias because the exact cause of death is not always easy to ascertain. To minimize the risk of bias, the event should be recorded as death from lymphoma, or from toxicity from the drug. Death from unknown causes should be attributed to the drug. For certain trials, time to next lymphoma treatment may be of interest, defined as time from the end of primary treatment until the initiation of the next therapy.
- Progression-free survival [ Time Frame: Up to 52 weeks ]Progression-free Survival (PFS) is defined as the time from entry onto study until lymphoma progression or death from any cause. PFS reflects tumor growth and, therefore, occurs prior to the endpoint of overall survival. In addition, PFS is not confounded by the administration of subsequent therapy. Whether a prolongation of PFS represents direct clinical benefit or a surrogate for clinical benefit depends on the magnitude of the effect and the risk-benefit ratio of the therapy under investigation. Unlike survival, the precise date of progression is generally unknown. It may be defined as the first date of documentation of a new lesion or enlargement of a previous lesion, or the date of the scheduled clinic visit immediately after radiologic assessment has been completed. Where there is missing information, censoring of the data may be defined as the last date at which progression status was adequately assessed or the first date of unscheduled new anti-lymphoma treatment.
- Time to progression [ Time Frame: Up to 52 weeks ]Time to progression (TTP) is defined as the time from study entry until lymphoma progression or death due to lymphoma. In TTP, deaths from other causes are censored either at the time of death or at an earlier time of assessment, representing a random pattern of loss from the study. TTP is not as useful as PFS unless the majority of deaths on a study are unrelated to the lymphoma due to the efficacy of the treatment and/or prolonged follow up
- Time to treatment failure [ Time Frame: Up to 52 weeks ]Time to treatment failure (event-free survival) is measured from the time from study entry to any treatment failure including discontinuation of treatment for any reason, such as disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death. This composite endpoint is generally not encouraged by regulatory agencies because it combines efficacy, toxicity and patient withdrawal.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02846935
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Brian Hill, MD, PhD||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|