Bortezomib in Treating Patients With Lymphoproliferative Disorders

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00023764
• Collaborator: (none)
• Enrollment: 103
• Location: 1
• Arm: 1
• Duration (Months): 93
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

Phase II trial to study the effectiveness of bortezomib in treating patients who have low-grade lymphoproliferative disorders. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma	Drug: bortezomib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the frequency and duration of complete and partial response rates in patients with grade I, II, or III follicular lymphoma or mantle cell lymphoma treated with bortezomib.

SECONDARY OBJECTIVES:

1. Determine the response of minimal residual disease by polymerase chain reaction (PCR) detectable or clonotypic PCR minimal residual disease in bone marrow of patients treated with this regimen.

2. Determine the time to progression and overall survival of patients treated with this regimen.

3. Determine the toxic effects of this regimen in these patients.

OUTLINE: Patients are stratified according to disease type (follicular lymphoma vs mantle cell lymphoma).

Patients receive an infusion of bortezomib over 3-5 seconds once weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.

Patients are followed every 3 months for 1 year and then every 4 months for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of PS-341 in Low Grade Lymphoproliferative Disorders
• Study Start Date: Jun 1, 2001
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive an infusion of bortezomib (dose of 1.8 mg/m2) over 3-5 seconds once weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.	Drug: bortezomib; Given IV; Other Names: LDP 341 MLN341 VELCADE

Outcome Measures

Primary Outcome Measures

1. Response Rate [Up to 3 years]

   The response probability will be estimated. The 95% confidence interval will be provided.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed lymphoproliferative disorder of 1 of the following subtypes:

• • Relapsed or refractory grade I, II, or III follicular center cell lymphoma

• Relapsed or refractory mantle cell lymphoma

• Measurable disease for non-Hodgkin's lymphoma (NHL) only

• At least 1 unidimensionally measurable lesion

• At least 2 cm by conventional techniques OR at least 1 cm by spiral CT scan

• Lymph nodes no greater than 1 cm in short axis considered normal

• Absolute lymphocytosis greater than 5,000/mm^3 with B-cell phenotype (CD19, 20,or 23 positive) with more than 30% bone marrow lymphocytes for CLL or other leukemic forms of NHL

• No known brain metastases

• Performance status - Karnofsky 70-100%

• At least 3 months

• See Disease Characteristics

• Absolute neutrophil count greater than 1,500/mm^{3 (500/mm}3 if lymphomatous involvement of bone marrow)

• Platelet count greater than 50,000/mm^3

• Bilirubin less than 1.5 times upper limit of normal (ULN)

• AST and ALT no greater than 2.5 times ULN (4 times ULN in case of liver metastases)

• Creatinine less than 1.5 times ULN

• No symptomatic congestive heart failure

• No New York Heart Association class III or IV heart disease

• No unstable angina pectoris

• No cardiac arrhythmia

• No myocardial infarction within the past 6 months

• No cerebrovascular accident or transient ischemic attack within the past 6 months

• No history of orthostatic hypotension

• No evidence of acute ischemia or significant conduction abnormality (left anterior hemiblock in the presence of right bundle branch block or second or third degree atrioventricular blocks) on electrocardiogram

• No uncontrolled hypertension requiring antihypertensive medication

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Febrile episodes up to 38.5°C allowed if no evidence of active infection

• No other uncontrolled concurrent illness

• No known or active HIV infection

• No ongoing or active infection

• No psychiatric illness or social situation that would preclude study entry

• At least 3 months since prior monoclonal antibody therapy (e.g., rituximab)

• No more than 3 prior regimens of conventional cytotoxic chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• At least 1 week since prior steroid therapy

• At least 4 weeks since prior radiotherapy and recovered

• At least 4 weeks since prior major surgery

• No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: John Gerecitano, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00023764
• Other Study ID Numbers: NCI-2012-01406; NCI-2012-01406; UNMC-03903; MSKCC-01049; NCI-2795; CDR0000068860; CWRU-MSKCC-1Y02; 01-049; 2795; P30CA008748; U01CA062502; N01CM62206
• First Posted: Jan 27, 2003
• Last Update Posted: Dec 8, 2015
• Last Verified: Dec 1, 2012

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoproliferative Disorders; Recurrence; Bortezomib

Study Results

Participant Flow

Recruitment Details	Protocol Open to Accrual 06/21/2001 Protocol Closed to Accrual 03/11/2008 Primary Completion Date 03/10/2009 Recruitment Location is the medical clinic

Arm/Group Title	PS-341 (Bortezomib)
Arm/Group Description	Patients receive an infusion of bortezomib over 3-5 seconds two times a week for two weeks or once weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.
Period Title: Overall Study
STARTED	103
COMPLETED	89
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	PS-341 (Bortezomib)
Arm/Group Description	Patients receive an infusion of bortezomib over 3-5 seconds two times a week for two weeks or once weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.
Overall Participants	103
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	47 45.6%
>=65 years	56 54.4%
Sex: Female, Male (Count of Participants)
Female	38 36.9%
Male	65 63.1%
Region of Enrollment (participants) [Number]
United States	103 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	The response probability will be estimated. The 95% confidence interval will be provided.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PS-341 (Bortezomib)-Relapsed Patients	PS-341 (Bortezomib)-Refractory Patients
Arm/Group Description	Patients receive an infusion of bortezomib over 3-5 seconds two times a week for two weeks or once weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.	Patients receive an infusion of bortezomib over 3-5 seconds two times a week for two weeks or once weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.
Measure Participants	23	14
Number [participants]	11 10.7%	6 NaN

Adverse Events

Arm/Group Title	PS-341 (Bortezomib)
Arm/Group Description	Patients receive an infusion of bortezomib over 3-5 seconds two times a week for two weeks or once weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.
All Cause Mortality
	PS-341 (Bortezomib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PS-341 (Bortezomib)
	Affected / at Risk (%)	# Events
Total	20/103 (19.4%)
Cardiac disorders
Arrhythmia	1/103 (1%)	1
Cardiac disorder	2/103 (1.9%)	2
Gastrointestinal disorders
Abdominal pain	3/103 (2.9%)	3
Constipation	3/103 (2.9%)	3
Ileus	1/103 (1%)	1
Nausea	2/103 (1.9%)	2
Vomiting	1/103 (1%)	1
General disorders
Fatigue	2/103 (1.9%)	2
Fever	2/103 (1.9%)	2
Pain	1/103 (1%)	1
Infections and infestations
Infection, NOS	4/103 (3.9%)	4
Skin infection	1/103 (1%)	1
Investigations
Platelet count decrease	2/103 (1.9%)	2
Weight loss	1/103 (1%)	1
Metabolism and nutrition disorders
Dehydration	2/103 (1.9%)	2
Hypocalcemia	2/103 (1.9%)	2
Hyponatremia	1/103 (1%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness	1/103 (1%)	1
Nervous system disorders
Neurological disorder	1/103 (1%)	1
peripheral motor neuropathy	1/103 (1%)	1
Renal and urinary disorders
Renal failure	1/103 (1%)	1
Respiratory, thoracic and mediastinal disorders
Chest pain	1/103 (1%)	1
Dyspnea	5/103 (4.9%)	5
Pleural effusion	1/103 (1%)	1
Pneumonitis	1/103 (1%)	1
Respiratory disorder	1/103 (1%)	1
Skin and subcutaneous tissue disorders
Rash desquamating	1/103 (1%)	1
Vascular disorders
Hypotension	1/103 (1%)	1
Other (Not Including Serious) Adverse Events
	PS-341 (Bortezomib)
	Affected / at Risk (%)	# Events
Total	95/103 (92.2%)
Blood and lymphatic system disorders
Anemia (Hemoglobin decrease)	72/103 (69.9%)	72
Gastrointestinal disorders
Abdominal pain	7/103 (6.8%)	7
Constipation	22/103 (21.4%)	22
Diarrhea	30/103 (29.1%)	30
Dyspepsia	6/103 (5.8%)	6
Nausea	25/103 (24.3%)	25
Vomiting	12/103 (11.7%)	12
General disorders
Edema	5/103 (4.9%)	5
Fatigue	33/103 (32%)	33
Fever	6/103 (5.8%)	6
Pain, other	7/103 (6.8%)	7
Rigors, chills	6/103 (5.8%)	6
Investigations
Alkaline Phosphatase	25/103 (24.3%)	25
Bilirubin	25/103 (24.3%)	25
Creatinine	24/103 (23.3%)	24
White blood cell decrease	51/103 (49.5%)	51
Lymphocyte count decreased	41/103 (39.8%)	41
Neutrophil count decreased	43/103 (41.7%)	43
PT	11/103 (10.7%)	11
PTT	10/103 (9.7%)	10
Platelet count decrease	84/103 (81.6%)	84
Aspartate aminotransferase increase	34/103 (33%)	34
Alanine aminotransferase increase	28/103 (27.2%)	28
Weight loss	5/103 (4.9%)	5
Metabolism and nutrition disorders
Anorexia	8/103 (7.8%)	8
Hyperglycemia	73/103 (70.9%)	73
Hyperkalemia	17/103 (16.5%)	17
Hypernatremia	19/103 (18.4%)	19
Hypoalbuminemia	38/103 (36.9%)	38
Hypocalcemia	37/103 (35.9%)	37
Hypoglycemia	11/103 (10.7%)	11
Hypokalemia	13/103 (12.6%)	13
Hypomagnesemia	7/103 (6.8%)	7
Hyponatremia	27/103 (26.2%)	27
Hypophosphatemia	11/103 (10.7%)	11
Nervous system disorders
Dizziness	10/103 (9.7%)	10
Headache	7/103 (6.8%)	7
Neuropathy-peripheral	14/103 (13.6%)	14
Neuropathy-sensory	39/103 (37.9%)	39
Psychiatric disorders
Insomnia	5/103 (4.9%)	5
Respiratory, thoracic and mediastinal disorders
Cough	7/103 (6.8%)	7
Dyspnea	8/103 (7.8%)	8
Pharyngeal mucositis	5/103 (4.9%)	5
Skin and subcutaneous tissue disorders
Rash	11/103 (10.7%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.