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

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00651755
First received: March 31, 2008
Last updated: June 28, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention
Lymphoma
Drug: Aprepitant
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Drug: Rituximab
Drug: Ondansetron

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Aprepitant's Effect on Drug Metabolism in Multi-Day Combination (CHOP/R-CHOP) Chemotherapy Regimen in Patients With Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Geometric Mean Area Under Curve (AUC) of Analyte, Cyclophosphamide (CP), in Aprepitant Treatment and Control Group [ Time Frame: Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle) ] [ Designated as safety issue: No ]
    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).

  • Geometric Mean Area Under Curve (AUC) of Analyte, 2-dechloro-cyclophosphamide(2-deCI-CP), in Aprepitant Treatment and Control Group [ Time Frame: Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle) ] [ Designated as safety issue: No ]
    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).

  • Geometric Mean Area Under Curve (AUC) of Analyte, 4-hydroxy-cyclophosphamide (4-OH-CP), in Aprepitant Treatment and Control Group [ Time Frame: Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle) ] [ Designated as safety issue: No ]
    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).

  • Geometric Mean Area Under Curve (AUC) of Analyte, Vincristine (VC), in Aprepitant Treatment and Control Group [ Time Frame: Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle) ] [ Designated as safety issue: No ]
    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).

  • Geometric Mean Area Under Curve (AUC) of Analyte,Prednisone (PR), in Aprepitant Treatment and Control Group [ Time Frame: Time points over 8 hours of cyclophosphamide infusion for both cycles (21 day cycle) ] [ Designated as safety issue: No ]
    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).

  • Geometric Mean Area Under Curve (AUC) of Analyte, Prednisolone (PL), in Aprepitant Treatment and Control Group [ Time Frame: Time points over 8 hours of cyclophosphamide infusion for both cycles (21 day cycle) ] [ Designated as safety issue: No ]
    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).


Enrollment: 23
Study Start Date: March 2008
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aprepitant + CHOP/R-CHOP
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
125 mg By Mouth (PO) On Day 1, followed by 80 mg PO Daily On Days 2-3.
Other Names:
  • Emend
  • L754030
  • MK869
Drug: Cyclophosphamide
750 mg/m^2 By Vein On Day 1
Other Names:
  • Cytoxan
  • Neosar
Drug: Doxorubicin
25 mg/m^2 By Vein Over 48 Hours On Days 1-2
Other Names:
  • AD
  • Hydroxydaunomycin hydrochloride
Drug: Vincristine
2 mg By Vein On Day 1
Drug: Prednisone
100 mg PO for 5 Days
Drug: Rituximab
375 mg/m^2 By Vein On Day 1.
Other Name: Rituxan
Experimental: Standard of Care (Control) + CHOP/R-CHOP
Anti-emetics, Ondansetron 8 mg daily for 2 days, plus steroids in CHOP or R-CHOP regimen.
Drug: Cyclophosphamide
750 mg/m^2 By Vein On Day 1
Other Names:
  • Cytoxan
  • Neosar
Drug: Doxorubicin
25 mg/m^2 By Vein Over 48 Hours On Days 1-2
Other Names:
  • AD
  • Hydroxydaunomycin hydrochloride
Drug: Vincristine
2 mg By Vein On Day 1
Drug: Prednisone
100 mg PO for 5 Days
Drug: Rituximab
375 mg/m^2 By Vein On Day 1.
Other Name: Rituxan
Drug: Ondansetron
8 mg daily for 2 days

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Newly diagnosed or relapsed lymphoid malignancy.
  2. 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
  3. Age >/= to 18 years
  4. 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.

Exclusion Criteria:

  1. Evidence of neoplastic central nervous system disease
  2. Patients who are unable to take oral medication (e.g. due to tumor obstruction)
  3. 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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00651755

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Saroj Vadhan-Raj, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00651755     History of Changes
Other Study ID Numbers: 2006-1033
Study First Received: March 31, 2008
Results First Received: February 8, 2013
Last Updated: June 28, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Doxorubicin
Prednisone
Vincristine
Ondansetron
Aprepitant
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 10, 2014