Doxorubicin Pharmacokinetics and Response in Non Hodgkin's Lymphoma

Association Between Response to Aggressive Chemotherapy and Doxorubicin Pharmacokinetics in Non Hodgkin's Lymphoma Patients

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.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Doxorubicin

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
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Kfar-Saba, Israel, 44281
    • Departmetn of Medicine. Meir Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Doxorubicin; Single arm	Drug: Doxorubicin; measurements of serum Doxorubicin levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Doxorubicin, pharmacokinetics at first chemotherapy course	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Association between doxorubicin pharmacokinetics and response	1 year

Collaborators and Investigators

• Sponsor: Meir Medical Center
• Investigators: Principal Investigator: Avishay Elis, MD, Meir Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: August 17, 2009
• First Submitted That Met QC Criteria: August 31, 2009
• First Posted (Estimate): September 1, 2009

Study Record Updates

• Last Update Posted (Estimate): July 1, 2013
• Last Update Submitted That Met QC Criteria: June 27, 2013
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: response; pharmacokinetics; Doxorubicin; non-Hodgkin's lymphoma; association between response to chemotherapy; myelosuppression degree; doxorubicin pharmacokinetics
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: 1. NHL; non