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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Case Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01959477
First received: October 8, 2013
Last updated: August 8, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Adult Grade III Lymphomatoid Granulomatosis
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Childhood Burkitt Lymphoma
Childhood Diffuse Large Cell Lymphoma
Childhood Grade III Lymphomatoid Granulomatosis
Childhood Immunoblastic Large Cell Lymphoma
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Contiguous Stage II Adult Burkitt Lymphoma
Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Contiguous Stage II Adult Lymphoblastic Lymphoma
Contiguous Stage II Grade 1 Follicular Lymphoma
Contiguous Stage II Grade 2 Follicular Lymphoma
Contiguous Stage II Grade 3 Follicular Lymphoma
Contiguous Stage II Mantle Cell Lymphoma
Contiguous Stage II Marginal Zone Lymphoma
Contiguous Stage II Small Lymphocytic Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Adult Burkitt Lymphoma
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Hairy Cell Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Stage I Adult Burkitt Lymphoma
Stage I Adult Diffuse Large Cell Lymphoma
Stage I Adult Diffuse Mixed Cell Lymphoma
Stage I Adult Diffuse Small Cleaved Cell Lymphoma
Stage I Adult Hodgkin Lymphoma
Stage I Adult Immunoblastic Large Cell Lymphoma
Stage I Adult Lymphoblastic Lymphoma
Stage I Adult T-cell Leukemia/Lymphoma
Stage I Childhood Anaplastic Large Cell Lymphoma
Stage I Childhood Hodgkin Lymphoma
Stage I Childhood Large Cell Lymphoma
Stage I Childhood Lymphoblastic Lymphoma
Stage I Childhood Small Noncleaved Cell Lymphoma
Stage I Cutaneous T-cell Non-Hodgkin Lymphoma
Stage I Grade 1 Follicular Lymphoma
Stage I Grade 2 Follicular Lymphoma
Stage I Grade 3 Follicular Lymphoma
Stage I Mantle Cell Lymphoma
Stage I Marginal Zone Lymphoma
Stage I Small Lymphocytic Lymphoma
Stage IA Mycosis Fungoides/Sezary Syndrome
Stage IB Mycosis Fungoides/Sezary Syndrome
Stage II Adult Hodgkin Lymphoma
Stage II Adult T-cell Leukemia/Lymphoma
Stage II Childhood Anaplastic Large Cell Lymphoma
Stage II Childhood Hodgkin Lymphoma
Stage II Childhood Large Cell Lymphoma
Stage II Childhood Lymphoblastic Lymphoma
Stage II Childhood Small Noncleaved Cell Lymphoma
Stage II Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IIA Mycosis Fungoides/Sezary Syndrome
Stage IIB Mycosis Fungoides/Sezary Syndrome
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Adult T-cell Leukemia/Lymphoma
Stage III Childhood Anaplastic Large Cell Lymphoma
Stage III Childhood Hodgkin Lymphoma
Stage III Childhood Large Cell Lymphoma
Stage III Childhood Lymphoblastic Lymphoma
Stage III Childhood Small Noncleaved Cell Lymphoma
Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Small Lymphocytic Lymphoma
Stage IIIA Mycosis Fungoides/Sezary Syndrome
Stage IIIB Mycosis Fungoides/Sezary Syndrome
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Adult T-cell Leukemia/Lymphoma
Stage IV Childhood Anaplastic Large Cell Lymphoma
Stage IV Childhood Hodgkin Lymphoma
Stage IV Childhood Large Cell Lymphoma
Stage IV Childhood Lymphoblastic Lymphoma
Stage IV Childhood Small Noncleaved Cell Lymphoma
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Stage IVA Mycosis Fungoides/Sezary Syndrome
Stage IVB Mycosis Fungoides/Sezary Syndrome
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Waldenström Macroglobulinemia
Drug: busulfan
Drug: etoposide
Drug: cyclophosphamide
Procedure: peripheral blood stem cell transplantation
Procedure: autologous hematopoietic stem cell transplantation
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Personalized Monitoring of Intravenous Busulfan Dosing for Patients With Lymphoma Undergoing Autologous Stem Cell Transplantation.

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • Proportion of patients who would not have achieved desired busulfan level with weight-based busulfan dosing [ Time Frame: Up to day -6 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: March 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: busulfan
Given IV
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
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
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous peripheral blood 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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01959477

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Brian T. Hill, MD    216-445-9451    hillb2@ccf.org   
Principal Investigator: Brian T. Hill         
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Brian Hill, MD Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01959477     History of Changes
Other Study ID Numbers: CASE1412, NCI-2013-01829, CASE 1412, P30CA043703
Study First Received: October 8, 2013
Last Updated: August 8, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia, Hairy Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Mantle-Cell
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Leukemia, B-Cell
Neoplasms, Plasma Cell
Burkitt Lymphoma
Hodgkin Disease
Immunoblastic Lymphadenopathy
Intraocular Lymphoma
Leukemia
Leukemia, Large Granular Lymphocytic
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Mycoses
Mycosis Fungoides
Sezary Syndrome
Syndrome

ClinicalTrials.gov processed this record on November 24, 2014