Brief Title
Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant
Official Title
Personalized Monitoring of Intravenous Busulfan Dosing for Patients With Lymphoma Undergoing Autologous Stem Cell Transplantation.
Brief Summary
This clinical trial studies personalized dose monitoring of busulfan and combination
chemotherapy in treating patients with Hodgkin or non-Hodgkin lymphoma undergoing stem cell
transplant. Giving chemotherapy before a stem cell transplant stops the growth of cancer
cells by stopping them from dividing or killing them. After treatment, stem cells are
collected from the patient's peripheral blood or bone marrow and stored. The stem cells are
then returned to the patient to replace the blood-forming cells that were destroyed by the
chemotherapy. Monitoring the dose of busulfan may help doctors deliver the most accurate dose
and reduce toxicity in patients undergoing stem cell transplant.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the feasibility of real-time therapeutic dose monitoring (TDM) for once daily
intravenously (IV) busulfan administration as part of a preparative regimen for patients with
lymphoma undergoing autologous stem cell transplantation.
SECONDARY OBJECTIVES:
I. To compare the incidence of adverse events including mucositis, liver toxicity, seizures,
and pulmonary toxicity with TDM of once daily IV busulfan compared to historic controls.
II. To compare the 6-month progression-free survival (PFS), with TDM of once daily IV
busulfan compared to historic controls.
III. To determine the proportion of patients who would not have achieved desired busulfan
level with weight-based busulfan dosing and therefore required TDM.
OUTLINE:
Patients receive busulfan intravenously (IV) over 3 hours on days -9 to -6, etoposide IV
continuously over 24-36 hours on days -5 and -4, and cyclophosphamide IV over 4 hours on days
-3 and -2. Patients then undergo autologous stem cell transplant on day 0.
After completion of study treatment, patients are followed up for 6 months.
Study Phase
Early Phase 1
Study Type
Interventional
Primary Outcome
Feasibility of performing real-time TDM, determined by the proportion of enrolled patients who are able to have an area under curve (AUC) for busulfan calculated
Secondary Outcome
Incidence of adverse events including mucositis, liver toxicity, seizures, and pulmonary toxicity, graded using NCI CTCAE version 4.0
Condition
Adult Grade III Lymphomatoid Granulomatosis
Intervention
busulfan
Study Arms / Comparison Groups
Treatment (busulfan, etoposide, cyclophosphamide, transplant)
Description: Patients receive busulfan IV over 3 hours on days -9 to -6, etoposide IV continuously over 24-36 hours on days -5 and -4, and cyclophosphamide IV over 4 hours on days -3 and -2. Patients then undergo autologous stem cell transplant on day 0.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
33
Start Date
March 2014
Completion Date
April 2015
Primary Completion Date
January 2015
Eligibility Criteria
Inclusion Criteria:
- Patients with either Hodgkin lymphoma or non-Hodgkin lymphoma
- Patients with a previously harvested hematopoietic stem cells while in complete or
partial remission, or in the case of patients with stable or refractory disease are
undergoing autologous transplantation because it has been recommended by their
treating physician as representing their best treatment option with a goal of at
minimum of 2 x 10^6 cluster of differentiation (CD)34+ peripheral primed stem cells
per kilogram of actual body weight
- Cardiac ejection fraction >= 45% or clearance by Cleveland Clinic (CCF) physician
- Diffusion capacity of the lung for carbon monoxide (DLCO) of >= 45% predicted or
clearance by CCF physician
- Serum creatinine < 2.0 mg/dl
- Serum bilirubin < 2.0 mg/dl
- Females of childbearing potential must have a negative pregnancy test
- Patients of childbearing potential must agree to use an effective birth control method
- Patient must not have any other active malignancy (or malignancy must be in remission
with no evidence of disease for the past 2 years) excluding nonmelanoma skin cancer
- Patients must have had at least 17 days since their most recent cytoxic chemotherapy
or radiation at the time of the initiation of their preparative regimen (day -9)
- Serum glutamic oxaloacetic transaminase (SGOT) < 2 times the normal or clearance by a
CCF physician
- Patients who are human immunodeficiency virus (HIV) positive:
- Patients must be receiving concurrent HAART therapy (highly active antiretroviral
therapy)
- CD4 count must be >= 100/mm^3
- Viral load must be =< 10,000 copies/ml
- Patients must not have concurrent opportunistic infections
- There is no restriction on the number of prior chemotherapeutic regimens or radiation
exposure with the exception of prior autologous or allogeneic stem cell
transplantation
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 at time of consent
- Subjects must have the ability to understand and the willingness to sign a written
informed consent document
Exclusion Criteria:
- Patients who have not recovered from adverse events due to agents administered more
than 4 weeks earlier OR
- Prior treatment toxicities must be resolved to =< grade 1 according to National
Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
version 4.0
- Patients with uncontrolled seizures as defined by having any seizure activity within
the 3 months prior to screening
- Patients who are receiving any other investigational agents
- Patients with untreated brain metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to busulfan other agents used in this study
- Patients receiving any medications or substances that are inhibitors or inducers of
specify cytochrome P450 (CYP450) enzyme(s) will be eligible for the study at the
discretion of the consenting physician
- Patients with uncontrolled intercurrent illness including, but not limited to ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements
- Pregnant or breastfeeding women are excluded from this study; breastfeeding should be
discontinued if the mother is treated with busulfan, cyclophosphamide, and etoposide
- Patients who have had major surgical procedures or significant traumatic injury within
28 days prior to study treatment
Gender
All
Ages
2 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Brian Hill, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01959477
Organization ID
CASE1412
Secondary IDs
NCI-2013-01829
Responsible Party
Sponsor
Study Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Brian Hill, MD, Principal Investigator, Case Comprehensive Cancer Center
Verification Date
August 2015