VELCADE®-BEAM and Autologous Hematopoietic Stem Cell Transplantation for Non-Hodgkin's Lymphoma, or Mantle Cell Lymphoma - Full Text View

Sponsors and Collaborators:	University of Nebraska Millennium Pharmaceuticals, Inc.
Information provided by:	University of Nebraska
ClinicalTrials.gov Identifier:	NCT00571493

Purpose

This is a Phase I/II trial designed to study the toxicity and Maximum Tolerated Dose of VELCADE in combination with BEAM and autologous hematopoietic stem cell transplantation and to obtain a preliminary estimate of the response rate to this combination.

Condition	Intervention	Phase
Non-Hodgkin's Lymphoma Mantle Cell Lymphoma	Drug: Bortezomib Drug: BEAM Procedure: autologous peripheral blood stem cell transplantation	Phase I Phase II

MedlinePlus related topics: Lymphoma

Drug Information available for: Cytarabine Cytarabine hydrochloride Etoposide Carmustine Melphalan Etoposide phosphate Bortezomib Melphalan hydrochloride Sarcolysin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase I/II Study of VELCADE®-BEAM and Autologous Hematopoietic Stem Cell Transplantation for Relapsed Indolent Non-Hodgkin's Lymphoma, Transformed or Mantle Cell Lymphoma

Further study details as provided by University of Nebraska:

Primary Outcome Measures:

Maximum Tolerated Dose [ Time Frame: Dependent on dose limiting toxicities ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response rate [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
overall survival [ Time Frame: from first chemotherapy administered until death ] [ Designated as safety issue: No ]
event-free survival [ Time Frame: from therapy until relapse, progression, or death from any cause ] [ Designated as safety issue: No ]

Estimated Enrollment:	44
Study Start Date:	April 2006
Estimated Study Completion Date:	December 2009

Arms	Assigned Interventions
Dose cohort 1 - 4: Experimental 3 patients will be accrued in each dose cohort. Enrollment will start at Dose Cohort #1. If 0-1 patients experience a dose-limiting toxicity, the next dose cohort will be initiated. Escalation to a higher dose cohort will not commence before 2 patients have achieved engraftment on that dose cohort to evaluate for toxicities. If 2 of 3 patients in Dose Cohort #1-4 have a dose-limiting toxicity, 3 additional patients will be added to that dose level. If 3 of these 6 patients experience a dose limiting toxicity defined as grade > 2 on the Bearman scale, DLT will be reached. No further dose escalation will take place.	Drug: Bortezomib Velcade will be administered in four dose cohorts, 0.8 mg/m², 1.0mg/m², 1.3mg/m² and 1.5mg/m². Three patients will be accrued in each dose cohort with enrollment starting at dose cohort 1, 0.8mg/m². Subjects participating in this study will receive Velcade on Days -11, -8, -5, and -2. Drug: BEAM carmustine 300mg/m2, etoposide 100mg/m2 BID, cytarabine 100mg/m2 BID, melphalan 140mg/m2 BID Procedure: autologous peripheral blood stem cell transplantation Peripheral blood stem cells will be collected as per the discretion of the treating physician. Once an adequate number of CD34+ cells/kg have been collected (as per existing institutional guidelines) the patient will begin the preparative regimen with for transplant. On day 0 of treatment, the previously stored hematopoietic stem cells will be re-infused. The cells will be removed from the storage freezer, brought to the patient area, thawed in a 370C water bath, and administered intravenously through a central line to the patient. Patients will then be cared for as standard transplant patients.

Arms

Assigned Interventions

Dose cohort 1 - 4: Experimental

3 patients will be accrued in each dose cohort. Enrollment will start at Dose Cohort #1. If 0-1 patients experience a dose-limiting toxicity, the next dose cohort will be initiated. Escalation to a higher dose cohort will not commence before 2 patients have achieved engraftment on that dose cohort to evaluate for toxicities.

If 2 of 3 patients in Dose Cohort #1-4 have a dose-limiting toxicity, 3 additional patients will be added to that dose level. If 3 of these 6 patients experience a dose limiting toxicity defined as grade > 2 on the Bearman scale, DLT will be reached. No further dose escalation will take place.

Drug: Bortezomib

Velcade will be administered in four dose cohorts, 0.8 mg/m², 1.0mg/m², 1.3mg/m² and 1.5mg/m². Three patients will be accrued in each dose cohort with enrollment starting at dose cohort 1, 0.8mg/m². Subjects participating in this study will receive Velcade on Days -11, -8, -5, and -2.

Drug: BEAM

carmustine 300mg/m2, etoposide 100mg/m2 BID, cytarabine 100mg/m2 BID, melphalan 140mg/m2 BID

Procedure: autologous peripheral blood stem cell transplantation

Peripheral blood stem cells will be collected as per the discretion of the treating physician. Once an adequate number of CD34+ cells/kg have been collected (as per existing institutional guidelines) the patient will begin the preparative regimen with for transplant. On day 0 of treatment, the previously stored hematopoietic stem cells will be re-infused. The cells will be removed from the storage freezer, brought to the patient area, thawed in a 370C water bath, and administered intravenously through a central line to the patient. Patients will then be cared for as standard transplant patients.

Detailed Description:

Primary Objective: To evaluate in a phase I study the toxicity and MTD of the addition of VELCADE™ (bortezomib) to a standard BEAM autologous transplant regimen. The phase II portion of the study will determine a preliminary estimate of the response rate.

Secondary Objectives: To obtain a preliminary estimate of the response rate to this regimen. To obtain preliminary estimates of event-free and overall survival using this regimen.

Enrolled subjects will receive Velcade in combination with BEAM and Autologous Hematopoietic Stem Cell Transplantation (AHSCT). Phase I treatment will administer Velcade in four dose cohorts,in addition to the BEAM and AHSCT. Three patients will be accrued in each dose cohort with enrollment starting at dose cohort. These subjects will be evaluated to establish the maximum tolerated dose of Velcade in combination with BEAM autologous peripheral blood stem cell transplantation. Once established, the maximum tolerated dose will be utilized in treating an additional 20 subjects.

Follow-Up: Data collected will be utilized to obtain a preliminary estimate of the response rate, event-free and overall survival using this regimen.

Eligibility

Ages Eligible for Study:	19 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Persistent, relapsed or refractory indolent non-Hodgkin's lymphoma (Follicular grade I, II, or III), non-Hodgkin's lymphoma, composite lymphomas with ≥ 50% of tumor showing follicular histology, transformed follicular, lymphoplasmacytic, marginal zone lymphoma, small Lymphocytic Lymphoma (including T-cell subtypes), or mantle cell lymphoma that is relapsed, refractory, or in PR1 or CR1 (MCL only for CR1).
Age >19 years.
Signed written informed consent.
Expected survival duration of > six months.
Karnofsky Performance Status > 70.
Eligible patients must have: Liver functions < 3x upper limits of normal (ULN) unless due to disease; ANC > 500 cells/mm3 and Platelet Count > 50 mm3.
Patients > age 60 or with clinical signs of heart disease must have ejection fraction ≥ 45% LVEF.
Patients with clinical signs of pulmonary insufficiency must have DLCO to be measured at > 50% of predicted value.
Able to collect > 1.2 X 106/kg CD34+ cell for transplantation.
No serious disease or condition that, in the opinion of the investigator, would compromise the patient's ability to participate in the study.
Female patients must not be pregnant or lactating.
Male and female patients of reproductive potential must follow accepted birth control measures.

Exclusion Criteria:

Patients who are HIV seropositive
Serum creatinine >2.5mg/dL or calculated creatinine clearance ≤ 50ml/min
Total bilirubin >3 times upper limits of normal (unless due to Gilberts disease or malignancy), ALT and AST >4 times the upper limits of normal
Active infection at the time of transplant
Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
Patient has hypersensitivity to bortezomib, boron or mannitol.
Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00571493

Contacts

Contact: Susan Allen, RN

402-559-8155

msallen@unmc.edu

Locations

United States, Nebraska
University of Nebraska Medical Center, Section of Oncology/Hematology	Recruiting
Omaha, Nebraska, United States, 68198-7680
Principal Investigator: Julie M Vose, M.D.

Sponsors and Collaborators

University of Nebraska

Millennium Pharmaceuticals, Inc.

Investigators

Study Chair:

Julie M Vose, M.D.

University of Nebraska

More Information

UNMC Oncology Homepage This link exits the ClinicalTrials.gov site

Responsible Party:	University of Nebraska Medical Center ( Julie M. Vose, M.D. Pricipal Investigator )
Study ID Numbers:	UNMC-43805, IRB 438-05, Protocol# X05184
Study First Received:	December 11, 2007
Last Updated:	December 11, 2007
ClinicalTrials.gov Identifier:	NCT00571493
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Nebraska:

non-hodgkin's lymphoma
mantle cell lymphoma
BEAM
Velcade

Study placed in the following topic categories:

Melphalan
Immunoproliferative Disorders
Lymphoma, Mantle-Cell
Carmustine
Bortezomib
Lymphoma, small cleaved-cell, diffuse
Mantle cell lymphoma

Etoposide phosphate
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma
Etoposide
Cytarabine

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents

Therapeutic Uses
Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on January 13, 2009