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Phase 1 Study of Radiosensitization Using Bortezomib in Relapsed Non-Hodgkin's Lymphoma Patients Receiving Radioimmunotherapy

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ClinicalTrials.gov Identifier: NCT00777114
Recruitment Status : Completed
First Posted : October 22, 2008
Last Update Posted : August 13, 2018
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
GlaxoSmithKline
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:

This will be a multi-center, Phase I, dose-escalation study of bortezomib in combination with 131I-tositumomab in patients with relapsed non-Hodgkin's lymphoma. Bortezomib will be administered to patients twice weekly, with the first dose being given two days prior to the treatment dose of 131I-tositumomab, and the second dose two days after RIT for a total of 5 doses.

Patients will be enrolled and undergo standard staging studies, including history, physical examination, complete blood count, serum chemistries and LDH, TSH, HAMA, iliac crest bone marrow biopsy, and CT scans of the chest, abdomen and pelvis. All patients will provide written informed consent.

Bortezomib will be evaluated at 4 dose levels (0.30 mg/m2, 0.60 mg/m2, 0.90 mg/m2, and 1.2 mg/m2) and 131I-tositumomab at 2 dose levels (50 cGy and 75 cGy TBD). Bortezomib will be administrated the day prior to 131I-tositumomab and twice weekly thereafter for 4 doses in order to provide proteasome inhibition throughout the period of 131I-tositumomab activity. The intention is to use 131I-tositumomab at full dose if possible. Therefore, the 50cGy dose will be used only with the lowest dose of bortezomib in case of unexpected toxicities with the combination.

Dose levels will be as follow:

  1. 0.30mg/m2 bortezomib and 50cGy 131I-tositumomab,
  2. 0.30 mg/m2 bortezomib and 75 cGy 131I-tositumomab,
  3. 0.60 mg/m2 bortezomib and 75 cGy 131I-tositumomab,
  4. 0.90 mg/m2 bortezomib and 75 cGy 131I-tositumomab, and
  5. 1.2 mg/m2 bortezomib and 75 cGy 131I-tositumomab.

Condition or disease Intervention/treatment Phase
Non-Hodgkin's Lymphoma Drug: bortezomib, tositumomab Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study of Radiosensitization Using Bortezomib in Relapsed Non-Hodgkin's Lymphoma Patients Receiving Radioimmunotherapy
Actual Study Start Date : April 1, 2007
Actual Primary Completion Date : December 18, 2012
Actual Study Completion Date : December 18, 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Bortezomib

Arm Intervention/treatment
Experimental: All patients Drug: bortezomib, tositumomab
  1. 0.30mg/m2 bortezomib and 50cGy 131I-tositumomab,
  2. 0.30 mg/m2 bortezomib and 75 cGy 131I-tositumomab,
  3. 0.60 mg/m2 bortezomib and 75 cGy 131I-tositumomab,
  4. 0.90 mg/m2 bortezomib and 75 cGy 131I-tositumomab, and
  5. 1.2 mg/m2 bortezomib and 75 cGy 131I-tositumomab.




Primary Outcome Measures :
  1. The primary objectives of this study are to determine: a) The appropriate doses of bortezomib and 131I-tositumomab when used in combination. b) Toxicities of the combination treatment. [ Time Frame: throughout dose escalation treatments ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically proven relapsed or refractory MCL, DLBCL including subtypes mediastinal large B cell, centroblastic, immunoblastic, T cell rich B cell and anaplastic large B cell lymphoma, or low grade B cell NHL.
  • Patients must have received prior systemic therapy for their lymphoma.
  • Age >18 years.
  • Life expectancy of greater than 12 weeks
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients may not be receiving any other investigational agents.
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib or boron.
  • Previous radiation therapy to the maximum tissue tolerance at any site.
  • Previous autologous or allogeneic stem cell transplantation.
  • Involvement of the bone marrow of >25% by lymphoma.
  • Known involvement of the central nervous system by lymphoma. 17
  • Significant organ dysfunction, including hematologic (absolute neutrophil count <1500, platelets <150,000).
  • ECOG performance status >2.
  • Uncontrolled illness including, but not limited to, ongoing or active infection,symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • HIV infection.
  • Patient has a calculated or measured creatinine clearance of <20 mL/minute within 14 days before enrollment.
  • Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.
  • Myocardial infarction within 3 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), 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 β-human chorionic gonadotropin (β-hCG) 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 ClinicalTrials.gov identifier (NCT number): NCT00777114


Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Millennium Pharmaceuticals, Inc.
GlaxoSmithKline
Investigators
Principal Investigator: Jia Ruan, MD, PhD Weill Medical College of Cornell University

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00777114     History of Changes
Obsolete Identifiers: NCT00398762
Other Study ID Numbers: 0806009862
First Posted: October 22, 2008    Key Record Dates
Last Update Posted: August 13, 2018
Last Verified: August 2018

Keywords provided by Weill Medical College of Cornell University:
relapsed non-Hodgkin's lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bortezomib
Antineoplastic Agents