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

NCT00571493 | Completed Phase 1 Results DMC

• 2 other identifiers: 0438-05-FBProtocol# X05184
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-hodgkin's Lymphoma; Mantle Cell Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  14 months

Secondary Outcomes (2)

• Preliminary Estimate of Overall Response Rate (ORR)

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

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

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

Study Arms (1)

Bortezomib Dose Escalation

EXPERIMENTAL

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; Drug: BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan)

Interventions

Bortezomib DRUG

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.

Also known as: Velcade

Bortezomib Dose Escalation

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

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.

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

Bortezomib Dose Escalation

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Nebraska: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell

Interventions

Bortezomib; Carmustine; Etoposide; Cytarabine; Melphalan

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Julie M Vose
• Organization: University of Nebraska Medical Center

jmvose@unmc.edu

402-559-3848

Study Officials

• Julie M Vose, MD

  University of Nebraska

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2007
• First Posted: December 12, 2007
• Study Start: April 14, 2006
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: September 28, 2023
• Results First Posted: July 26, 2018

Record last verified: 2023-09

Locations

US (1)