Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant

August 12, 2015 updated by: Case Comprehensive Cancer Center

Personalized Monitoring of Intravenous Busulfan Dosing for Patients With Lymphoma Undergoing Autologous Stem Cell Transplantation.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

33

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (busulfan, etoposide, cyclophosphamide, transplant)
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.
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: busulfan
Given IV
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous peripheral blood stem cell transplant
Procedure: peripheral blood stem cell transplantation
Undergo autologous peripheral blood stem cell transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: Up to day -6
Up to day -6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events including mucositis, liver toxicity, seizures, and pulmonary toxicity, graded using NCI CTCAE version 4.0
Time Frame: Up to 100 days after treatment
Incidence of adverse events will be compared to historic controls. For comparison, categorical variables will be summarized as frequency counts and percentages and compared between historical controls that were treated with weight-based busulfan with those enrolled as part of the clinical trial who receive busulfan TDM. Continuous variables will be summarized as the mean, standard deviation, median, and range and compared using the Wilcoxon rank sum test.
Up to 100 days after treatment
Proportion of patients who would not have achieved desired busulfan level with weight-based busulfan dosing
Time Frame: Up to day -6
Up to day -6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Case Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Brian Hill, MD, Case Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

October 8, 2013

First Submitted That Met QC Criteria

October 8, 2013

First Posted (Estimate)

October 10, 2013

Study Record Updates

Last Update Posted (Estimate)

August 13, 2015

Last Update Submitted That Met QC Criteria

August 12, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CASE1412
  • P30CA043703 (U.S. NIH Grant/Contract)
  • NCI-2013-01829 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • CASE 1412 (Other Identifier: Case Comprehensive Cancer Center)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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