Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation
Study Details
Study Description
Brief Summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with rituximab may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib and rituximab together works in treating patients with mantle cell lymphoma who have previously undergone stem cell transplantation
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- To evaluate the two year disease free survival in mantle cell lymphoma (MCL) patients treated with bortezomib + rituximab after hematopoietic stem cell transplantation (HSCT).
SECONDARY OBJECTIVES:
- To evaluate the toxicity profile, safety, overall survival, time to treatment failure, remission duration, and biological markers of mantle cell lymphoma patients treated with bortezomib + rituximab after autologous hematopoietic stem cell transplantation.
OUTLINE: Patients receive bortezomib subcutaneously (SC) or intravenously (IV) over 3-5 seconds and rituximab IV on days 1, 8, 15, and 22. Treatment with bortezomib repeats every 3 months for up to 8 courses and treatment with rituximab repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 3 years.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment (bortezomib and rituximab) Doses of bortezomib given is 1.3 mg/m2 weekly x 4 weeks given every 3 month x 8 cycles. Doses of RITUXAN given is 375 mg/m2 give weekly x 4 weeks given every 6 month for 4 cycles. |
Drug: bortezomib
Given SC or IV
Other Names:
Biological: rituximab
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: immunohistochemistry staining method
Correlative studies
Other Names:
Genetic: RNA analysis
Correlative studies
Genetic: gene expression analysis
Correlative studies
Genetic: DNA analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
Other: pharmacogenomic studies
Correlative studies
Other Names:
Other: Questionnaire Administration
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Two-year Disease-free Survival [Up to five years after initial treatment]
Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula.
Secondary Outcome Measures
- Two-year Overall Survival [Up to five years after initial treatment]
Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula.
- Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment [Up to five years after initial treatment]
Observed toxicities will be summarized in terms of type, severity (graded by NCI CTCAE version 4.0) and attribution.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have histological documented or cytological confirmed mantle cell lymphoma; cyclin D1 must be present as evidenced by either fluorescence in situ hybridization (FISH) or immunohistochemical staining
-
Patients must have undergone autologous hematopoietic stem cell transplantation (AHCT) and achieved engraftment by day (D)60-180 as evidenced by absolute neutrophil count (ANC) > 1000/mcL and platelets (Plt) > 75,000/mcL
-
Patients must be in complete remission at D60-180 after AHCT as evidenced by computed tomography (CT) scan of the neck/chest/abdomen (abd)/pelvis or CT/positron emission tomography (PET) scans
-
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
-
Life expectancy of greater than 3 months
-
Karnofsky > 60%
-
ANC > 1000/mcL
-
Plts > 75,000/mcL
-
Total bilirubin within normal institutional limits, patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible
-
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x institutional upper limit of normal
-
Creatinine up to and including 2 mg/dL
Exclusion Criteria:
-
Patient has >= grade 2 peripheral neuropathy within 14 days before enrollment and at D60-180 after AHCT; patients who had >= grade 2 peripheral neuropathy within 14 days before enrollment but resolves to grade 1 or lower peripheral neuropathy at D60-D180 after AHCT can be enrolled at this time
-
Patient has > 1.5 x upper limit of normal (ULN) total bilirubin unless history of Gilbert's syndrome
-
Myocardial infarction within 6 months prior to enrollment or has New York Heart 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 electrocardiographic (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 beta-human chorionic gonadotropin (beta-hCG) 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 treatment of treatment with bortezomib + rituximab
-
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
-
Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
-
Patients with other active malignancies (no evidence of other cancer or life expectancy greater than 5 years) are ineligible for this study
-
Human immunodeficiency virus (HIV) positive patients or hepatitis B or C positive patients
-
Patients with active central nervous system (CNS) disease or history of brain metastases (mets) are excluded from study
-
Prior exposure to either bortezomib or rituximab is not an exclusion criteria
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | City of Hope Medical Center | Duarte | California | United States | 91010 |
2 | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- City of Hope Medical Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Matthew Mei, City of Hope Medical Center
Study Documents (Full-Text)
More Information
Publications
None provided.- 10137
- NCI-2010-02343
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Treatment (Bortezomib and Rituximab) |
---|---|
Arm/Group Description | Doses of bortezomib given is 1.3 mg/m2 weekly x 4 weeks given every 3 month x 8 cycles. Doses of RITUXAN given is 375 mg/m2 give weekly x 4 weeks given every 6 month for 4 cycles. bortezomib: Given SC or IV rituximab: Given IV laboratory biomarker analysis: Correlative studies immunohistochemistry staining method: Correlative studies RNA analysis: Correlative studies gene expression analysis: Correlative studies DNA analysis: Correlative studies pharmacological study: Correlative studies pharmacogenomic studies: Correlative studies Questionnaire Administration |
Period Title: Overall Study | |
STARTED | 23 |
COMPLETED | 23 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Treatment (Bortezomib and Rituximab) |
---|---|
Arm/Group Description | Doses of bortezomib given is 1.3 mg/m2 weekly x 4 weeks given every 3 month x 8 cycles. Doses of RITUXAN given is 375 mg/m2 give weekly x 4 weeks given every 6 month for 4 cycles. bortezomib: Given SC or IV rituximab: Given IV laboratory biomarker analysis: Correlative studies immunohistochemistry staining method: Correlative studies RNA analysis: Correlative studies gene expression analysis: Correlative studies DNA analysis: Correlative studies pharmacological study: Correlative studies pharmacogenomic studies: Correlative studies Questionnaire Administration |
Overall Participants | 23 |
Age (years) [Median (Full Range) ] | |
Median (Full Range) [years] |
59
|
Sex: Female, Male (Count of Participants) | |
Female |
1
4.3%
|
Male |
22
95.7%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
6
26.1%
|
Not Hispanic or Latino |
17
73.9%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
1
4.3%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
0
0%
|
White |
21
91.3%
|
More than one race |
0
0%
|
Unknown or Not Reported |
1
4.3%
|
Region of Enrollment (participants) [Number] | |
United States |
23
100%
|
Outcome Measures
Title | Two-year Disease-free Survival |
---|---|
Description | Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula. |
Time Frame | Up to five years after initial treatment |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Bortezomib and Rituximab) |
---|---|
Arm/Group Description | Doses of bortezomib given is 1.3 mg/m2 weekly x 4 weeks given every 3 month x 8 cycles. Doses of RITUXAN given is 375 mg/m2 give weekly x 4 weeks given every 6 month for 4 cycles. bortezomib: Given SC or IV rituximab: Given IV |
Measure Participants | 23 |
Number (95% Confidence Interval) [percentage of survival] |
90
|
Title | Two-year Overall Survival |
---|---|
Description | Assessed by Kaplan-Meier survival analysis. 95% confidence intervals will be calculated using Greenwood's formula. |
Time Frame | Up to five years after initial treatment |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Bortezomib and Rituximab) |
---|---|
Arm/Group Description | Doses of bortezomib given is 1.3 mg/m2 weekly x 4 weeks given every 3 month x 8 cycles. Doses of RITUXAN given is 375 mg/m2 give weekly x 4 weeks given every 6 month for 4 cycles. bortezomib: Given SC or IV rituximab: Given IV |
Measure Participants | 23 |
Number (95% Confidence Interval) [percentage of survival] |
95
|
Title | Grade 3 or 4 Toxicities of Bortezomib and Rituximab Treatment |
---|---|
Description | Observed toxicities will be summarized in terms of type, severity (graded by NCI CTCAE version 4.0) and attribution. |
Time Frame | Up to five years after initial treatment |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Bortezomib and Rituximab) |
---|---|
Arm/Group Description | Doses of bortezomib given is 1.3 mg/m2 weekly x 4 weeks given every 3 month x 8 cycles. Doses of RITUXAN given is 375 mg/m2 give weekly x 4 weeks given every 6 month for 4 cycles. bortezomib: Given SC or IV rituximab: Given IV |
Measure Participants | 23 |
Neutropenia |
17
73.9%
|
Lymphopenia |
8
34.8%
|
Pneumonia |
2
8.7%
|
Anemia |
2
8.7%
|
Lung infection |
2
8.7%
|
Skin infection |
1
4.3%
|
Wound infection |
1
4.3%
|
Hypertension |
1
4.3%
|
Thrombocytopenia |
1
4.3%
|
Adverse Events
Time Frame | Up to five years after initial treatment | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Treatment (Bortezomib and Rituximab) | |
Arm/Group Description | Doses of bortezomib given is 1.3 mg/m2 weekly x 4 weeks given every 3 month x 8 cycles. Doses of RITUXAN given is 375 mg/m2 give weekly x 4 weeks given every 6 month for 4 cycles. bortezomib: Given SC or IV rituximab: Given IV | |
All Cause Mortality |
||
Treatment (Bortezomib and Rituximab) | ||
Affected / at Risk (%) | # Events | |
Total | 3/23 (13%) | |
Serious Adverse Events |
||
Treatment (Bortezomib and Rituximab) | ||
Affected / at Risk (%) | # Events | |
Total | 7/23 (30.4%) | |
Blood and lymphatic system disorders | ||
Myelodysplastic Syndrome | 1/23 (4.3%) | 1 |
General disorders | ||
Fever | 2/23 (8.7%) | 2 |
Infections and infestations | ||
Skin Infection | 1/23 (4.3%) | 1 |
Wound Infection | 1/23 (4.3%) | 1 |
Lung Infection | 1/23 (4.3%) | 1 |
Human Metapneumovirus Infection | 1/23 (4.3%) | 1 |
Febrile Neutropenia | 1/23 (4.3%) | 1 |
Meningitis | 1/23 (4.3%) | 1 |
Investigations | ||
Neutrophil Count Decreased | 1/23 (4.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Treatment (Bortezomib and Rituximab) | ||
Affected / at Risk (%) | # Events | |
Total | 23/23 (100%) | |
Blood and lymphatic system disorders | ||
Anemia | 15/23 (65.2%) | 46 |
Blood and lymphatic system disorders - Other, specify | 1/23 (4.3%) | 1 |
Febrile neutropenia | 1/23 (4.3%) | 1 |
Cardiac disorders | ||
Atrial fibrillation | 1/23 (4.3%) | 1 |
Sinus bradycardia | 2/23 (8.7%) | 2 |
Sinus tachycardia | 1/23 (4.3%) | 1 |
Ear and labyrinth disorders | ||
Hearing impaired | 6/23 (26.1%) | 7 |
Tinnitus | 5/23 (21.7%) | 6 |
Endocrine disorders | ||
Endocrine disorders - Other, specify | 2/23 (8.7%) | 2 |
Eye disorders | ||
Blurred vision | 1/23 (4.3%) | 1 |
Dry eye | 1/23 (4.3%) | 1 |
Eye disorders - Other, specify | 3/23 (13%) | 4 |
Watering eyes | 2/23 (8.7%) | 3 |
Gastrointestinal disorders | ||
Abdominal pain | 4/23 (17.4%) | 4 |
Bloating | 3/23 (13%) | 4 |
Constipation | 3/23 (13%) | 4 |
Diarrhea | 11/23 (47.8%) | 16 |
Gastrointestinal disorders - Other, specify | 1/23 (4.3%) | 3 |
Mucositis oral | 1/23 (4.3%) | 1 |
Nausea | 6/23 (26.1%) | 9 |
Vomiting | 3/23 (13%) | 4 |
General disorders | ||
Chills | 8/23 (34.8%) | 9 |
Edema limbs | 4/23 (17.4%) | 5 |
Fatigue | 21/23 (91.3%) | 38 |
Fever | 9/23 (39.1%) | 13 |
Flu like symptoms | 2/23 (8.7%) | 2 |
Gait disturbance | 3/23 (13%) | 5 |
Injection site reaction | 8/23 (34.8%) | 9 |
Non-cardiac chest pain | 1/23 (4.3%) | 1 |
Pain | 5/23 (21.7%) | 5 |
Immune system disorders | ||
Allergic reaction | 1/23 (4.3%) | 1 |
Immune system disorders - Other, specify | 2/23 (8.7%) | 3 |
Infections and infestations | ||
Eye infection | 1/23 (4.3%) | 1 |
Infections and infestations - Other, specify | 1/23 (4.3%) | 1 |
Lung infection | 3/23 (13%) | 4 |
Skin infection | 3/23 (13%) | 3 |
Upper respiratory infection | 7/23 (30.4%) | 12 |
Wound infection | 1/23 (4.3%) | 1 |
Injury, poisoning and procedural complications | ||
Bruising | 1/23 (4.3%) | 1 |
Fall | 1/23 (4.3%) | 1 |
Vascular access complication | 1/23 (4.3%) | 1 |
Investigations | ||
Alanine aminotransferase increased | 8/23 (34.8%) | 23 |
Alkaline phosphatase increased | 4/23 (17.4%) | 5 |
Aspartate aminotransferase increased | 9/23 (39.1%) | 19 |
Blood bilirubin increased | 1/23 (4.3%) | 1 |
Cholesterol high | 1/23 (4.3%) | 1 |
Creatinine increased | 6/23 (26.1%) | 17 |
Investigations - Other, specify | 5/23 (21.7%) | 37 |
Lymphocyte count decreased | 12/23 (52.2%) | 84 |
Neutrophil count decreased | 20/23 (87%) | 67 |
Platelet count decreased | 17/23 (73.9%) | 59 |
Weight gain | 2/23 (8.7%) | 3 |
White blood cell decreased | 20/23 (87%) | 89 |
Metabolism and nutrition disorders | ||
Anorexia | 4/23 (17.4%) | 4 |
Hypercalcemia | 1/23 (4.3%) | 2 |
Hyperglycemia | 5/23 (21.7%) | 10 |
Hyperkalemia | 4/23 (17.4%) | 6 |
Hypermagnesemia | 2/23 (8.7%) | 3 |
Hypernatremia | 4/23 (17.4%) | 5 |
Hypertriglyceridemia | 1/23 (4.3%) | 1 |
Hyperuricemia | 2/23 (8.7%) | 2 |
Hypoalbuminemia | 2/23 (8.7%) | 2 |
Hypocalcemia | 6/23 (26.1%) | 10 |
Hypoglycemia | 3/23 (13%) | 5 |
Hypokalemia | 3/23 (13%) | 4 |
Hypomagnesemia | 2/23 (8.7%) | 2 |
Hyponatremia | 6/23 (26.1%) | 9 |
Hypophosphatemia | 5/23 (21.7%) | 8 |
Obesity | 1/23 (4.3%) | 2 |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 9/23 (39.1%) | 14 |
Back pain | 5/23 (21.7%) | 6 |
Flank pain | 1/23 (4.3%) | 1 |
Generalized muscle weakness | 4/23 (17.4%) | 4 |
Muscle weakness lower limb | 1/23 (4.3%) | 1 |
Musculoskeletal and connective tissue disorder - Other, specify | 5/23 (21.7%) | 6 |
Myalgia | 4/23 (17.4%) | 4 |
Pain in extremity | 3/23 (13%) | 4 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Myelodysplastic syndrome | 1/23 (4.3%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 2/23 (8.7%) | 2 |
Nervous system disorders | ||
Dizziness | 2/23 (8.7%) | 2 |
Headache | 3/23 (13%) | 5 |
Paresthesia | 6/23 (26.1%) | 6 |
Peripheral motor neuropathy | 1/23 (4.3%) | 1 |
Peripheral sensory neuropathy | 13/23 (56.5%) | 26 |
Vasovagal reaction | 1/23 (4.3%) | 1 |
Psychiatric disorders | ||
Agitation | 1/23 (4.3%) | 1 |
Anxiety | 5/23 (21.7%) | 6 |
Depression | 2/23 (8.7%) | 2 |
Insomnia | 1/23 (4.3%) | 1 |
Libido decreased | 1/23 (4.3%) | 1 |
Psychiatric disorders - Other, specify | 1/23 (4.3%) | 1 |
Renal and urinary disorders | ||
Hematuria | 1/23 (4.3%) | 1 |
Proteinuria | 1/23 (4.3%) | 1 |
Reproductive system and breast disorders | ||
Breast pain | 2/23 (8.7%) | 2 |
Gynecomastia | 1/23 (4.3%) | 1 |
Reproductive system and breast disorders - Other, specify | 1/23 (4.3%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Allergic rhinitis | 1/23 (4.3%) | 1 |
Cough | 9/23 (39.1%) | 19 |
Dyspnea | 2/23 (8.7%) | 3 |
Nasal congestion | 7/23 (30.4%) | 10 |
Pleural effusion | 1/23 (4.3%) | 1 |
Postnasal drip | 1/23 (4.3%) | 1 |
Productive cough | 9/23 (39.1%) | 10 |
Sore throat | 8/23 (34.8%) | 11 |
Wheezing | 1/23 (4.3%) | 1 |
Skin and subcutaneous tissue disorders | ||
Dry skin | 2/23 (8.7%) | 2 |
Hyperhidrosis | 2/23 (8.7%) | 2 |
Pruritus | 3/23 (13%) | 3 |
Rash acneiform | 1/23 (4.3%) | 1 |
Rash maculo-papular | 4/23 (17.4%) | 5 |
Skin and subcutaneous tissue disorders - Other, specify | 5/23 (21.7%) | 6 |
Skin hyperpigmentation | 1/23 (4.3%) | 1 |
Skin ulceration | 2/23 (8.7%) | 2 |
Vascular disorders | ||
Hot flashes | 1/23 (4.3%) | 1 |
Hypertension | 17/23 (73.9%) | 43 |
Hypotension | 1/23 (4.3%) | 1 |
Limitations/Caveats
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.
Results Point of Contact
Name/Title | Dr. Matthew Mei |
---|---|
Organization | City of Hope |
Phone | 626-359-8111 |
mamei@coh.org |
- 10137
- NCI-2010-02343