Doxorubicin Pharmacokinetics and Response in Non Hodgkin's Lymphoma | RxWiki

Doxorubicin Pharmacokinetics and Response in Non Hodgkin's Lymphoma

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Purpose	In previous studies, the investigators found that in patients with Hodgkin's lymphoma (HL) treated with ABVD (adriamycin, bleomycin, vinblastine and decarbazine) the absence of alopecia may predict for a poor response to treatment [complete remission (CR) rate 79% versus 31%, P < 0.0005, respectively]. Also, patients without alopecia had fewer episodes of either leucopenia, neutropenia, deferral of treatment courses or number of courses with dose reduction [88% vs. 62.5%, P=0.05, for the presence of at least one of them]. One of the explanations for this phenomenon is related to a lower systemic exposure of chemotherapeutic drugs in patients who retain their hair. There is a wide interpatient variability in the pharmacokinetic and pharmacodynamic parameters of doxorubicin systemic exposure and the degree of myelosuppression. In a pilot study on 18 patients the investigators could not find the previous association between alopecia, response to chemotherapy and bone marrow depression. However, when analyzing doxorubicin pharmacokinetics, patients who had no remission had 2 fold lower AUC (area under the curve) and 3 fold lower peaks (p=0.06). The investigators' lack to approve the previous findings might be explained by the small study group.
Condition	Non-Hodgkin's Lymphoma
Intervention	Drug: Doxorubicin
Phase	Phase 4
Sponsor	Meir Medical Center
Responsible Party	Meir Medical Center
ClinicalTrials.gov Identifier	NCT00969462
First Received	August 17, 2009
Last Updated	June 27, 2013
Last verified	March 2012

Tracking Information[ + expand ][ + ]

First Received Date	August 17, 2009
Last Updated Date	June 27, 2013
Start Date	September 2009
Estimated Primary Completion Date	December 2012
Current Primary Outcome Measures	Doxorubicin, pharmacokinetics at first chemotherapy course [Time Frame: 1 year] [Designated as safety issue: No]
Current Secondary Outcome Measures	Association between doxorubicin pharmacokinetics and response [Time Frame: 1 year] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	Doxorubicin Pharmacokinetics and Response in Non Hodgkin's Lymphoma
Official Title	Association Between Response to Aggressive Chemotherapy and Doxorubicin Pharmacokinetics in Non Hodgkin's Lymphoma Patients
Brief Summary	In previous studies, the investigators found that in patients with Hodgkin's lymphoma (HL) treated with ABVD (adriamycin, bleomycin, vinblastine and decarbazine) the absence of alopecia may predict for a poor response to treatment [complete remission (CR) rate 79% versus 31%, P < 0.0005, respectively]. Also, patients without alopecia had fewer episodes of either leucopenia, neutropenia, deferral of treatment courses or number of courses with dose reduction [88% vs. 62.5%, P=0.05, for the presence of at least one of them]. One of the explanations for this phenomenon is related to a lower systemic exposure of chemotherapeutic drugs in patients who retain their hair. There is a wide interpatient variability in the pharmacokinetic and pharmacodynamic parameters of doxorubicin systemic exposure and the degree of myelosuppression. In a pilot study on 18 patients the investigators could not find the previous association between alopecia, response to chemotherapy and bone marrow depression. However, when analyzing doxorubicin pharmacokinetics, patients who had no remission had 2 fold lower AUC (area under the curve) and 3 fold lower peaks (p=0.06). The investigators' lack to approve the previous findings might be explained by the small study group.
Detailed Description	Aim of the study: To evaluate the association between response to chemotherapy, the degree of myelosuppression and the pharmacokinetics of doxorubicin in non-Hodgkin's lymphoma (NHL) patients. Methods: Study protocol: 1. At diagnosis Demographic and clinical parameters be collected (Appendix 1) 2. At course 2: 1. Doxorubicin will be given by 5-7 minutes infusion before the other medications (Doxorubicin doses will be collected (Appendix 1)) 2. Blood will be sampled in course 2, at: 0 minutes 30 minutes 120 minutes 24 hours Two 2ml EDT tubes will be drawn at each time The tubes will be centrifuged at 3000 RPM for 15 min. Plasma samples will be stored in - 700C 3. At the end of chemotherapy courses the following data will be collected (Appendix 2): 1. Episodes of bone marrow depression (leucopenia, neutropenia) Treatment delays Dose reductions Neutropenic fever 2. Remission status [Complete remission (CR) - disappearance of clinical signs and symptoms of NHL along with normal laboratory and radiological findings]. 4. At the end of one year of CR Remission status Number of patients: 30
Study Type	Interventional
Study Phase	Phase 4
Study Design	Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Non-Hodgkin's Lymphoma
Intervention	Drug: Doxorubicin measurements of serum Doxorubicin levels
Study Arm (s)	No Intervention: Doxorubicin Single arm

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	18
Estimated Completion Date	December 2012
Estimated Primary Completion Date	December 2011
Eligibility Criteria	Inclusion Criteria: - Age ≥ 18 years - Biopsy proven intermediate grade NHL - No previous chemotherapy - At least 4 courses of R-CHOP at maximal doses are planned - An informed consent Exclusion Criteria: - Do not meet all inclusion criteria
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Israel

Administrative Information[ + expand ][ + ]

NCT Number	NCT00969462
Other Study ID Numbers	1. NHL
Has Data Monitoring Committee	No
Information Provided By	Meir Medical Center
Study Sponsor	Meir Medical Center
Collaborators	Not Provided
Investigators	Principal Investigator: Avishay Elis, MD Meir Medical Center
Verification Date	March 2012

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