Doxorubicin Pharmacokinetics and Response in Non Hodgkin's Lymphoma

Non-Hodgkin's Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00969462
• Other study ID #: 1. NHL
• Secondary ID: non
• Status: Completed
• Phase: Phase 4
• First received: August 17, 2009
• Last updated: June 27, 2013
• Start date: September 2009
• Est. completion date: December 2012

Study information

• Verified date: March 2012
• Source: Meir Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: non
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• Doxorubicin
measurements of serum Doxorubicin levels

Locations

Country	Name	City	State
Israel	Departmetn of Medicine. Meir Medical Center	Kfar-Saba

Sponsors (1)

Lead Sponsor	Collaborator
Meir Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Doxorubicin, pharmacokinetics at first chemotherapy course		1 year	No
Secondary	Association between doxorubicin pharmacokinetics and response		1 year	No