Study of Standard-Dose Rituximab, Ifosfamide, Carboplatin and Etoposide

NCT01300793 | Terminated Phase 1 DMC

• 1 other identifier: 06253
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective of the study is to determine the maximum tolerated dose (MTD) of bortezomib (Velcade) in combination with rituximab, ifosfamide, carboplatin and etoposide for adult patients with relapsed or refractory aggressive B-cell lymphoma. The secondary objectives are to assess the tolerability and safety, the response rate, rate of autologous stem cell transplant and CD34+ progenitor cell collection and engraftment after treatment with this regimen.

Conditions

Non-Hodgkin's Lymphoma; B-cell Lymphoma

Keywords

V-RICE; Relapsed NHL; Primary Refractory NHL

Outcome Measures

Primary Outcomes (1)

• Determine the MTD of Velcade (bortezomib), Rituximab, Ifosfamide, Carboplatin, Etoposide (V-RICE) for patients with relapsed/primary refractory aggressive B-cell non-Hodgkin's lymphoma (NHL)

  5 years

Secondary Outcomes (1)

• tolerability and safety, response rate, the amount of peripheral blood CD34+ progenitor cells collected and the rate of engraftment, assess the rate of autologous stem cell transplant

  5 years

Interventions

Velcade (bortezomib), rituximab, ifosfamide, carboplatin, etoposide DRUG

Rituximab, 375 mg/m2, IV on day 1 Etoposide, 100 mg/m2, IV on days 2 to 4 Carboplatin, AUC 5 (using the Calvert Formula), IV on day 3 Ifosfamide, 5 g/m2 with Mesna 5 g/m2, CIV over 24 hours beginning D. 3 Bortezomib,1.0mg/m2 starting cohort. Based upon a satisfactory safety profile, additional pts. will be enrolled into the 1.3, 1.5 and 1.7mg/m2 cohorts given IVP over 3 sec. d. 1, 4, 8 \& 11 q. 28 days.

Also known as: Velcade, VP-16, Carboplatin, Rituxan, ifosfamide

Eligibility Criteria

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

You may qualify if:

• Aggressive B-cell non-Hodgkin lymphoma, CD-20 positive, in first relapse or refractory to first- or second-line chemotherapy (non-platinum)
• Diffuse large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma (Grade III), Transformed Follicular Lymphoma
• Prior Rituximab is allowed
• Prior radiation is allowed
• Prior autologous stem cell transplant is allowed
• Age 18-70 years
• ECOG performance status 0-2
• HIV seronegative
• No CNS involvement: CSF cytology is required for cases with bone marrow involvement, involvement of 2 or more extranodal sites, presentation in the testes or paranasal sinuses, or if any clinical suspicion of CNS involvement (e.g., cranial nerve deficits)
• Measurable disease on CT scan by international working group response criteria • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male subject agrees to use an acceptable method for contraception for the duration of the study.

You may not qualify if:

• Subject has a platelet count of less than 75,000.
• Subject has an absolute neutrophil count of less than 1000
• Subject has a calculated or measured creatinine clearance of \<60 mL/minute within 14 days before enrollment.
• Subject has grade 2 or greater peripheral neuropathy or grade 1 with pain within 14 days before enrollment.
• 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.
• Subject 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.
• Subject has been treated with more than two prior chemotherapy regimens
• Subject has been treated with a platinum-based regimen.
• Subject has received other investigational drugs with 14 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Unviersity of California Medical Center

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Interventions

Bortezomib; Rituximab; Ifosfamide; Carboplatin; Etoposide

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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Oxazines; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Lawrence Kaplan, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 24, 2009
• First Posted: February 23, 2011
• Study Start: May 1, 2007
• Primary Completion: July 1, 2011
• Study Completion: April 1, 2012
• Last Updated: September 26, 2012

Record last verified: 2012-09

Locations

US (1)