Aprepitant's Effect on Drug Metabolism in Multi-Day Combination (CHOP/R-CHOP) Chemotherapy Regimen in Lymphoma Patients

NCT00651755 | Completed Results DMC

• 1 other identifier: 2006-1033
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn the effect of combining aprepitant with CHOP or R-CHOP in patients with Non-Hodgkin's Lymphoma (NHL) that is either newly diagnosed or has come back. Researchers also want to see if aprepitant can help to prevent nausea and/or vomiting that may be caused by chemotherapy treatment with CHOP or R-CHOP, in these patients. CHOP consists of four drugs - Cyclophosphamide (also called Cytoxan/Neosar), Doxorubicin (or Adriamycin), Vincristine (Oncovin) and Prednisolone while R-CHOP includes Rituximab and CHOP.

Conditions

Lymphoma

Keywords

Non-Hodgkin's Lymphoma; Lymphoma; Nausea; Cyclophosphamide; Cytoxan; Neosar; Doxorubicin; AD; Hydroxydaunomycin hydrochloride; Vincristine; Prednisone; Rituximab; Rituxan; Aprepitant; Emend; L754030; MK869; Drug Metabolism; CHOP; R-CHOP; NHL

Outcome Measures

Primary Outcomes (6)

• Geometric Mean Area Under Curve (AUC) of Analyte, Cyclophosphamide (CP), in Aprepitant Treatment and Control Group

  Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of Cyclophosphamide (CP) during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. micrograms (ug)/milliliters (mL) times hour (hr).

  Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle)

• Geometric Mean Area Under Curve (AUC) of Analyte, 2-dechloro-cyclophosphamide(2-deCI-CP), in Aprepitant Treatment and Control Group

  Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of 2-deCI-CP, during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. micrograms (ug)/milliliters (mL) times hour (hr).

  Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle)

• Geometric Mean Area Under Curve (AUC) of Analyte, 4-hydroxy-cyclophosphamide (4-OH-CP), in Aprepitant Treatment and Control Group

  Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of 4-hydroxy-cyclophosphamide (4-OH-CP), during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. micrograms (ug)/milliliters (mL) times hour (hr).

  Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle)

• Geometric Mean Area Under Curve (AUC) of Analyte, Vincristine (VC), in Aprepitant Treatment and Control Group

  Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of VC, during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. nanograms (ng)/milliliters (mL) times hour (hr).

  Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle)

• Geometric Mean Area Under Curve (AUC) of Analyte,Prednisone (PR), in Aprepitant Treatment and Control Group

  Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of PR, during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. nanograms (ng)/milliliters (mL) times hour (hr).

  Time points over 8 hours of cyclophosphamide infusion for both cycles (21 day cycle)

• Geometric Mean Area Under Curve (AUC) of Analyte, Prednisolone (PL), in Aprepitant Treatment and Control Group

  Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of PL, during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. nanograms (ng)/milliliters (mL) times hour (hr).

  Time points over 8 hours of cyclophosphamide infusion for both cycles (21 day cycle)

Study Arms (2)

Aprepitant + CHOP/R-CHOP

EXPERIMENTAL

Aprepitant 125 mg oral (PO) Day 1 of Cycle 1 followed by 80 mg PO Daily Days 2-3 with CHOP (steroid in CHOP) or R-CHOP plus Rituximab 375 mg/m\^2 intravenous Day 1. CHOP or R-CHOP chemotherapy: (1) bolus or 48-hour infusion CHOP \[cyclophosphamide 750 mg/m\^2 IV Day 1, doxorubicin 25 mg/m\^2/day IV given bolus or over 48 hours continuous infusion Days 1-2, vincristine 2 mg IV Day 1, prednisone PO 100 mg \* 5 days\]; or (2) Bolus or 48-hour infusion R-CHOP \[Rituximab 375 mg/m\^2 on Day 1 + CHOP as above\]. \[For patients receiving R-CHOP, CHOP may be administered starting on Day 2 at the discretion of the treating physician\]

Drug: Aprepitant; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Rituximab

Standard of Care (Control) + CHOP/R-CHOP

EXPERIMENTAL

Anti-emetics, Ondansetron 8 mg daily for 2 days, plus steroids in CHOP or R-CHOP regimen.

Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Rituximab; Drug: Ondansetron

Interventions

Aprepitant DRUG

125 mg By Mouth (PO) On Day 1, followed by 80 mg PO Daily On Days 2-3.

Also known as: Emend, L754030, MK869

Aprepitant + CHOP/R-CHOP

Cyclophosphamide DRUG

750 mg/m\^2 By Vein On Day 1

Also known as: Cytoxan, Neosar

Aprepitant + CHOP/R-CHOP; Standard of Care (Control) + CHOP/R-CHOP

Doxorubicin DRUG

25 mg/m\^2 By Vein Over 48 Hours On Days 1-2

Also known as: AD, Hydroxydaunomycin hydrochloride

Aprepitant + CHOP/R-CHOP; Standard of Care (Control) + CHOP/R-CHOP

Vincristine DRUG

2 mg By Vein On Day 1

Aprepitant + CHOP/R-CHOP; Standard of Care (Control) + CHOP/R-CHOP

Prednisone DRUG

100 mg PO for 5 Days

Aprepitant + CHOP/R-CHOP; Standard of Care (Control) + CHOP/R-CHOP

Rituximab DRUG

375 mg/m\^2 By Vein On Day 1.

Also known as: Rituxan

Aprepitant + CHOP/R-CHOP; Standard of Care (Control) + CHOP/R-CHOP

Ondansetron DRUG

8 mg daily for 2 days

Standard of Care (Control) + CHOP/R-CHOP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed or relapsed lymphoid malignancy.
• Patients receiving either:(1) Bolus or 48-hr infusion CHOP (cyclophosphamide 750 mg/m\^2 IV Day 1, doxorubicin 25 mg/m\^2/day IV given as bolus infusion or over 48 hours continuous infusion Days 1-2, vincristine 2 mg IV Day 1, prednisone PO 100 mg \* 5 days) OR (2) Bolus or 48-hr infusion R-CHOP (Rituximab 375mg/m\^2 on Day 1+ CHOP as above). (For patients receiving R-CHOP, CHOP may be administered starting on Day 2 at the discretion of the treating physician
• Age \>/= to 18 years
• Adequate organ function defined as serum total bilirubin \</= 1.2 mg/dL, serum aspartate aminotransferase or serum glutamate oxaloacetate transaminase (SGOT) \</= 60 IU/L, creatinine \< 1.5 mg/dL.

You may not qualify if:

• Evidence of neoplastic central nervous system disease
• Patients who are unable to take oral medication (e.g. due to tumor obstruction)
• History of Diabetes Mellitus (Diabetes as defined by established diagnosis of diabetes currently receiving medications for the diabetes management and/or a fasting blood glucose of \>/= 126 mg/dL.)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Lymphoma; Lymphoma, Non-Hodgkin; Nausea

Interventions

Aprepitant; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; Rituximab; Ondansetron

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Imidazoles; Azoles; Carbazoles; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Saroj Vadhan-Raj, MD / Professor
• Organization: University of Texas MD Anderson Cancer Center

xzhou@mdanderson.org

Study Officials

• Saroj Vadhan-Raj, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2008
• First Posted: April 3, 2008
• Study Start: March 1, 2008
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: July 2, 2013
• Results First Posted: July 2, 2013

Record last verified: 2013-06

Locations

US (1)