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

September 13, 2023 updated by: University of Nebraska

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

This is a Phase I/II trial designed to study the toxicity and Maximum Tolerated Dose (MTD) of bortezomib in combination with BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT) and to obtain a preliminary estimate of the response rate to this combination.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary Objective:The primary objective of the study is to evaluate the toxicity and determine the maximum tolerated dose (MTD) of bortezomib when added to a standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) conditioning regimen followed by autologous hematopoietic stem cell transplantation (ASCT).

Secondary Objective: The secondary objective of the study is to obtain a preliminary estimate of the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) with this regimen.

Enrolled subjects will receive bortezomib in combination with BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (AHSCT). Phase I treatment will administer bortezomib in four dose cohorts,in addition to the BEAM and ASCT. 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 bortezomib 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 overall response rate, progressions free survival and overall survival using this regimen.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 2
  • 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
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7680
        • University of Nebraska Medical 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

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bortezomib Dose Escalation

The phase I section of the study will follow a standard 3 + 3 design to determine the maximum tolerated dose (MTD) of bortezomib when added to a standard BEAM (BCNU (carmustine), etoposide, cytarabine, melphalan) conditioning regimen followed by autologous hematopoietic stem cell transplantation (ASCT).

After the MTD is defined, additional patients will enroll in Phase II to obtain preliminary estimates of survival using the Phase I regimen.
Drug: Bortezomib
Patients will receive bortezomib in four dose cohorts ( .8. 1.0, 1.3, 1.5 mg/m²). Patients will receive bortezomib on days -11, -8, -5, and -2 before infusion of autologous stem cells.
Other Names:
  • Velcade
Drug: BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan)

All study patients will receive BEAM per the standard institution protocol:

BCNU (carmustine): 300 mg/m²on day -5 etoposide 100 mg/m² twice daily on days -5, -4, -3, and -2 cytarabine 100 mg/m² twice daily on days -5, -4, -3, -2 melphalan: 140 mg/m² on day -1 before infusion of autologous stem cells.

Other Names:
  • B - Carmustine (BCNU) E - Etoposide. A - Cytarabine (Ara-C, cytosine arabinoside) M - Melphalan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of Bortezomib
Time Frame: 14 months
The maximum tolerated dose (MTD) is defined to be the dose cohort below which 3 of 6 patients experience dose limiting toxicity (DLT), or the highest dose cohort of 1.5 mg/m², if 2 DLT were not observed at any dose cohort.
14 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preliminary Estimate of Overall Response Rate (ORR)
Time Frame: 100 day post autologous hematopoietic stem cell transplantation (ASCT), one year post ASCT
To obtain a preliminary estimate of overall response rate (ORR). The overall response rate is calculated as the number of patients who achieved complete response (CR) and partial response (PR) divided by the total number of evaluable patients.
100 day post autologous hematopoietic stem cell transplantation (ASCT), one year post ASCT
Progression-free Survival (PFS), and Overall Survival (OS)
Time Frame: one year post autologous hematopoietic stem cell transplantation (ASCT) , 5 years post ASCT
To obtain a preliminary estimate of PFS and OS. Overall survival (OS) is defined as time from the first chemotherapy administered on the transplant trial until death from any cause. Progression free survival (PFS)is defined as time from therapy until relapse, progression, or death from any cause.
one year post autologous hematopoietic stem cell transplantation (ASCT) , 5 years post ASCT

Collaborators and Investigators

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

Sponsor

University of Nebraska

Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

  • Study Chair: Julie M Vose, MD, University of Nebraska

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 (Actual)

April 14, 2006

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

December 11, 2007

First Submitted That Met QC Criteria

December 11, 2007

First Posted (Estimated)

December 12, 2007

Study Record Updates

Last Update Posted (Actual)

September 28, 2023

Last Update Submitted That Met QC Criteria

September 13, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0438-05-FB
  • Protocol# X05184 (Other Grant/Funding Number: Millennium)

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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