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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00571493
Recruitment Status : Completed
First Posted : December 12, 2007
Last Update Posted : August 13, 2015
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska

Brief Summary:
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 or disease Intervention/treatment Phase
Non-hodgkin's Lymphoma Mantle Cell Lymphoma Drug: Bortezomib Drug: BEAM Procedure: autologous peripheral blood stem cell transplantation Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : April 2006
Actual Primary Completion Date : November 2014
Actual Study Completion Date : November 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Bortezomib
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Dose cohort 1 - 4

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.
Other Name: Velcade
Drug: BEAM
carmustine 300mg/m2, etoposide 100mg/m2 BID, cytarabine 100mg/m2 BID, melphalan 140mg/m2 BID
Other Names:
  • BCNU
  • VP-16
  • Ara-C
  • Melphalan
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.

Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: Dependent on dose limiting toxicities ]

Secondary Outcome Measures :
  1. Response rate [ Time Frame: Day 100 ]
  2. overall survival [ Time Frame: from first chemotherapy administered until death ]
  3. event-free survival [ Time Frame: from therapy until relapse, progression, or death from any cause ]

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Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00571493

United States, Nebraska
University of Nebraska Medical Center, Section of Oncology/Hematology
Omaha, Nebraska, United States, 68198-7680
Sponsors and Collaborators
University of Nebraska
Millennium Pharmaceuticals, Inc.
Study Chair: Julie M Vose, M.D. University of Nebraska

Responsible Party: Julie M Vose, MD, Professor & N/M Harris Oncology Professorship, University of Nebraska Identifier: NCT00571493     History of Changes
Other Study ID Numbers: 438-05
IRB 438-05
Protocol# X05184
First Posted: December 12, 2007    Key Record Dates
Last Update Posted: August 13, 2015
Last Verified: August 2015

Keywords provided by Julie M Vose, MD, University of Nebraska:
non-hodgkin's lymphoma
mantle cell lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs