Ofatumumab and Dinaciclib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia
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|ClinicalTrials.gov Identifier: NCT01515176|
Recruitment Status : Completed
First Posted : January 23, 2012
Results First Posted : March 15, 2018
Last Update Posted : March 15, 2018
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia Prolymphocytic Leukemia Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia||Drug: Dinaciclib Other: Laboratory Biomarker Analysis Biological: Ofatumumab Other: Pharmacological Study||Phase 1 Phase 2|
I. To determine the tolerable dose of combination therapy with ofatumumab and dinaciclib (phase 1b component) in chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), and B-cell prolymphocytic leukemia (B-PLL).
II. To characterize the toxicity of combination therapy with ofatumumab and dinaciclib in CLL/SLL/B-PLL.
III. To determine the overall response rate associated with this treatment as assessed by consensus response criteria. (Phase II)
I. To estimate progression-free survival (PFS) after combination treatment with ofatumumab and dinaciclib.
II. To characterize the pharmacokinetics of dinaciclib when given in combination with ofatumumab.
III. To correlate pharmacokinetic features of dinaciclib with response, toxicity (particularly tumor lysis syndrome), and pharmacodynamic endpoints.
IV. To perform detailed baseline and serial pharmacodynamic studies of combination therapy with ofatumumab and dinaciclib and correlate these with response to therapy.
V. To correlate baseline disease-risk parameters (i.e., zeta-chain-associated protein kinase [ZAP]-70 expression, interphase cytogenetics, immunoglobulin heavy chain variable region [IgVH] mutational analysis, and other clinical prognostic factors) with response to therapy.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive ofatumumab intravenously (IV) over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for up to 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1b/2 Study of Dinaciclib (SCH 727965) and Ofatumumab in Relapsed and Refractory CLL/SLL/B-PLL|
|Actual Study Start Date :||January 2012|
|Actual Primary Completion Date :||March 4, 2015|
|Actual Study Completion Date :||July 19, 2016|
Experimental: Treatment (ofatumumab, dinaciclib)
Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum-tolerated Dose of Dinaciclib When Given in Combination With Ofatumumab, Defined as a Dose Level Where at Most One of 6 Evaluable Patients Has a Dose Limiting Toxicity (Phase Ia) [ Time Frame: Day 56 ]Graded according to the National Cancer Institute (NCI) CTCAE version (v)4.0. Assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization.
- Number of Patients With Dose-limiting Toxicity Incidents Graded According to the NCI CTCAE v4.0 (Phase I) [ Time Frame: Up to day 56 ]Hematologic dose-limiting toxicity measures will be assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTCAE version 4 standard toxicity grading. Non-hematologic dose-limiting toxicities such as dyspnea and renal will be evaluated via the ordinal CTCAE standard toxicity grading only.
- Percentage of Patients Who Achieve an Overall Response, Defined as Achieving a Complete Response, an Unconfirmed Complete Response (SLL Only), or a Partial Response (Phase II) [ Time Frame: Up to 28 weeks ]Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Complete Response Rate [ Time Frame: Up to 28 weeks ]Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions
- Overall Survival [ Time Frame: Time from study entry to death due to any cause, assessed up to 5 years ]Distributions will be explored and assessed using the methods of Kaplan and Meier.
- Progression Free Survival [ Time Frame: Time from study entry to documentation of disease progression and/or death, assessed up to 5 years ]95% confidence intervals will be constructed using the methods of Duffy and Santner with the assumption that these rates are binomially distributed. Distributions will be explored and assessed using the methods of Kaplan and Meier.
- Time to Treatment Failure [ Time Frame: Time from study entry to the date patients end treatment, up to 28 weeks ]Distributions will be explored and assessed using the methods of Kaplan and Meier.
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): NCT01515176
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Kerry Rogers, MD||Ohio State University Comprehensive Cancer Center|