A Phase II Trial of Combined Weekly Bortezomib and Tositumomab I-131 in Patients With Relapsed or Refractory Follicular Non-Hodgkin's Lymphoma

• Sponsor: Rush University Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00479167
• Collaborator: GlaxoSmithKline (Industry), Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 16.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine what dose of bortezomib in combination with tositumomab I-131 is tolerable whether bortezomib and Tositumomab I-131 are effective in the treatment of relapsed or refractory non-hodgkin's lymphoma (NHL). Both agents are effective in treating relapsed and refractory NHL. Administer of the agents together may sensitize the cells to the radiation from Tositumomab I-131.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma	Drug: Bortezomib and Tositumomab I-131	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Combined Weekly Bortezomib and Tositumomab I-131 in Patients With Relapsed or Refractory Follicular Non-Hodg
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bortezomib and Tositumomab I-131	Drug: Bortezomib and Tositumomab I-131

Outcome Measures

Primary Outcome Measures

1. The Primary Objective of This Study is to Determine the Maximum Tolerated Dose (up to 1.6 mg/m2) of Bortezomib Combined With Tositumomab and Iodine I 131 Tositumomab [Study terminated.]

Secondary Outcome Measures

1. To Further Explore the Toxicity and Efficacy of Bortezomib Combined With Tositumomab and Iodine I 131 Tositumomab and Assess the Tolerability of Bortezomib After Tositumomab [Study Terminated.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Previously treated or relapsed follicular lymphoma. One prior therapy required.

• Bi-dimensionally measurable disease with at least one lesion measuring > 2.0 X 2.0cm by CT scan or evaluable disease.

• CD20+ at time of diagnosis or subsequently.

• Platelet count > 100,000/uL, ANC > 1000/uL.

• Transaminases less than two-fold normal range.

• Adequate renal function defined as <1.5 X upper limit of normal

• HAMA negative

• ECOG performance status 0, 1, 2.

• 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.

• Negative Hepatitis profile screening

Exclusion Criteria:

• Myocardial infarction within 6 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 boron or mannitol.

• Greater than 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens

• Hypocellular bone marrow (≤15% cellularity or marked reduction in bone marrow precursors).

• Prior myeloablative therapy.

• History of failed stem cell collection.

• Prior radiotherapy to fields encompassing more than 25% of the blood-forming marrow.

• Prior chemotherapy, biologic therapy, radiation therapy or steroid therapy for NHL within three weeks prior to screening procedures. Six weeks for nitrosureas. Subjects receiving low doses of steroids for non-neoplastic indications may enter the study ("low dose steroids" is defined as ≤10 mg of prednisone or equivalent per day).

• Prior Radioimmunotherapy or bortezomib.

• Prior malignancy other than lymphoma, except for adequately treated basal cell or squamous cell skin cancer, in situ uterine cervical cancer, or other cancer for which the subject has been disease-free for five years.

• Evidence of active infection requiring intravenous antibiotics at the time of study enrollment.

• Known HIV infection.

• Known brain or leptomeningeal metastases.

• Active obstructive hydronephrosis.

• Known Type I hypersensitivity or anaphylactic reactions to murine proteins or any component of the Iodine I 131 tositumomab therapeutic regimen.

• 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.

• Patient has received other investigational drugs with 14 days before enrollment

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

• Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush University Medical Center	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• Rush University Medical Center
• GlaxoSmithKline
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Stephanie A Gregory, MD, Rush University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

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• Buchsbaum DJ, Wahl RL, Normolle DP, Kaminski MS. Therapy with unlabeled and 131I-labeled pan-B-cell monoclonal antibodies in nude mice bearing Raji Burkitt's lymphoma xenografts. Cancer Res. 1992 Dec 1;52(23):6476-81.
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• Cusack JC Jr, Liu R, Houston M, Abendroth K, Elliott PJ, Adams J, Baldwin AS Jr. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res. 2001 May 1;61(9):3535-40.
• Davis TA, Grillo-López AJ, White CA, McLaughlin P, Czuczman MS, Link BK, Maloney DG, Weaver RL, Rosenberg J, Levy R. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's lymphoma: safety and efficacy of re-treatment. J Clin Oncol. 2000 Sep;18(17):3135-43.
• Demidem A, Lam T, Alas S, Hariharan K, Hanna N, Bonavida B. Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother Radiopharm. 1997 Jun;12(3):177-86.
• Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, Kalman L, Miller V, Lee JS, Moore M, Gandara D, Karp D, Vokes E, Kris M, Kim Y, Gamza F, Hammershaimb L. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000 Jun;18(12):2354-62. Erratum in: J Clin Oncol. 2004 Jan 1;22(1):209.
• Gallagher CJ, Gregory WM, Jones AE, Stansfeld AG, Richards MA, Dhaliwal HS, Malpas JS, Lister TA. Follicular lymphoma: prognostic factors for response and survival. J Clin Oncol. 1986 Oct;4(10):1470-80.
• Hideshima T, Richardson P, Chauhan D, Palombella VJ, Elliott PJ, Adams J, Anderson KC. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res. 2001 Apr 1;61(7):3071-6.
• Horning SJ. Natural history of and therapy for the indolent non-Hodgkin's lymphomas. Semin Oncol. 1993 Oct;20(5 Suppl 5):75-88. Review.
• Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Adams J, Kauffman M, Esseltine DL, Schenkein DP, Anderson KC. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004 Oct;127(2):165-72.
• Johnson PW, Rohatiner AZ, Whelan JS, Price CG, Love S, Lim J, Matthews J, Norton AJ, Amess JA, Lister TA. Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center. J Clin Oncol. 1995 Jan;13(1):140-7.
• Kaminski MS, Zasadny KR, Francis IR, Fenner MC, Ross CW, Milik AW, Estes J, Tuck M, Regan D, Fisher S, Glenn SD, Wahl RL. Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma. J Clin Oncol. 1996 Jul;14(7):1974-81.
• LeBlanc R, Catley LP, Hideshima T, Lentzsch S, Mitsiades CS, Mitsiades N, Neuberg D, Goloubeva O, Pien CS, Adams J, Gupta D, Richardson PG, Munshi NC, Anderson KC. Proteasome inhibitor PS-341 inhibits human myeloma cell growth in vivo and prolongs survival in a murine model. Cancer Res. 2002 Sep 1;62(17):4996-5000.
• Lightcap ES, McCormack TA, Pien CS, Chau V, Adams J, Elliott PJ. Proteasome inhibition measurements: clinical application. Clin Chem. 2000 May;46(5):673-83.
• McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93.
• McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825-33.
• Orlowski RZ, Stinchcombe TE, Mitchell BS, Shea TC, Baldwin AS, Stahl S, Adams J, Esseltine DL, Elliott PJ, Pien CS, Guerciolini R, Anderson JK, Depcik-Smith ND, Bhagat R, Lehman MJ, Novick SC, O'Connor OA, Soignet SL. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J Clin Oncol. 2002 Nov 15;20(22):4420-7.
• Press OW, Appelbaum F, Ledbetter JA, Martin PJ, Zarling J, Kidd P, Thomas ED. Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas. Blood. 1987 Feb;69(2):584-91.
• Press OW, Rasey J. Principles of radioimmunotherapy for hematologists and oncologists. Semin Oncol. 2000 Dec;27(6 Suppl 12):62-73. Review.
• Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994 Jan 15;83(2):435-45.
• Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003 Jun 26;348(26):2609-17.
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• Teicher BA, Ara G, Herbst R, Palombella VJ, Adams J. The proteasome inhibitor PS-341 in cancer therapy. Clin Cancer Res. 1999 Sep;5(9):2638-45.
• White CA, Weaver RL, Grillo-López AJ. Antibody-targeted immunotherapy for treatment of malignancy. Annu Rev Med. 2001;52:125-45. Review. Erratum in: Annu Rev Med 2002;53:xi.
• Young RC, Longo DL, Glatstein E, Ihde DC, Jaffe ES, DeVita VT Jr. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol. 1988 Apr;25(2 Suppl 2):11-6.
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• Responsible Party: Rush University Medical Center
• ClinicalTrials.gov Identifier: NCT00479167
• Other Study ID Numbers: LYM 2005-01
• First Posted: May 28, 2007
• Last Update Posted: Nov 4, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Rush University Medical Center: Non-Hodgkin's Lymphoma; Follicular Non-Hodgkin's Lymphoma; Lymphoma
• Additional relevant MeSH terms: Lymphoma; Bortezomib; Tositumomab I-131

Study Results

Participant Flow

Arm/Group Title	Bortezomib in Combination With Tositumomab
Arm/Group Description
Period Title: Overall Study
STARTED	1
COMPLETED	0
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Bortezomib in Combination With Tositumomab
Arm/Group Description
Overall Participants	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Age (years) []
Sex: Female, Male () []
Female
Male
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

Title	The Primary Objective of This Study is to Determine the Maximum Tolerated Dose (up to 1.6 mg/m2) of Bortezomib Combined With Tositumomab and Iodine I 131 Tositumomab
Time Frame	Study terminated.

Outcome Measure Data

Analysis Population Description

Subject withdrew

Arm/Group Title	Bortezomib Combined With Tositumomab and Iodine I 131 Tositumomab
Arm/Group Description	Bortezomib Combined With Tositumomab and Iodine I 131 Tositumomab
Measure Participants	0

2. Secondary Outcome

Title	To Further Explore the Toxicity and Efficacy of Bortezomib Combined With Tositumomab and Iodine I 131 Tositumomab and Assess the Tolerability of Bortezomib After Tositumomab
Time Frame	Study Terminated.

Outcome Measure Data

Analysis Population Description

Subject withdrew

Arm/Group Title	Bortezomib and Tositumomab I-131
Arm/Group Description	Bortezomib and Tositumomab I-131
Measure Participants	0

Adverse Events

Arm/Group Title	Bortezomib in Combination With Tositumomab
Arm/Group Description	Bortezomib in combination with tositumomab
All Cause Mortality
	Bortezomib in Combination With Tositumomab
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Bortezomib in Combination With Tositumomab
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Bortezomib in Combination With Tositumomab
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

Only 1 patient was on study and withdrew after 1 cycle. There was lack of interest in the study. The PI is now retiring.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.