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

Primary Purpose

Non-hodgkin's Lymphoma, Mantle Cell Lymphoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Bortezomib

BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan)

About this trial

This is an interventional treatment trial for Non-hodgkin's Lymphoma focused on measuring non-hodgkin's lymphoma, mantle cell lymphoma, BEAM, Velcade

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Nebraska Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bortezomib Dose Escalation

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of Bortezomib

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.

Secondary Outcome Measures

Preliminary Estimate of Overall Response Rate (ORR)

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.

Progression-free Survival (PFS), and Overall Survival (OS)

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.

Full Information

NCT ID

NCT00571493

First Posted

December 11, 2007

Last Updated

September 13, 2023

Sponsor

University of Nebraska

Collaborators

Millennium Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00571493

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

April 14, 2006 (Actual)

Primary Completion Date

November 1, 2014 (Actual)

Study Completion Date

November 1, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Nebraska

Collaborators

Millennium Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-hodgkin's Lymphoma, Mantle Cell Lymphoma

Keywords

non-hodgkin's lymphoma, mantle cell lymphoma, BEAM, Velcade

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Bortezomib Dose Escalation

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Bortezomib

Other Intervention Name(s)

Velcade

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan)

Other Intervention Name(s)

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

Intervention Description

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.

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) of Bortezomib

Description

Time Frame

14 months

Secondary Outcome Measure Information:

Title

Preliminary Estimate of Overall Response Rate (ORR)

Description

Time Frame

100 day post autologous hematopoietic stem cell transplantation (ASCT), one year post ASCT

Title

Progression-free Survival (PFS), and Overall Survival (OS)

Description

Time Frame

one year post autologous hematopoietic stem cell transplantation (ASCT) , 5 years post ASCT

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Julie M Vose, MD

Organizational Affiliation

University of Nebraska

Official's Role

Study Chair

Facility Information:

Facility Name

University of Nebraska Medical Center

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198-7680

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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