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Fenretinide and Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00288067
Recruitment Status : Terminated (NCI stopped supplying fenretinide in November of 2012.)
First Posted : February 7, 2006
Results First Posted : October 6, 2014
Last Update Posted : October 6, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma
B-cell Chronic Lymphocytic Leukemia
Contiguous Stage II Adult Burkitt Lymphoma
Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Contiguous Stage II Adult Lymphoblastic Lymphoma
Contiguous Stage II Grade 1 Follicular Lymphoma
Contiguous Stage II Grade 2 Follicular Lymphoma
Contiguous Stage II Mantle Cell Lymphoma
Stage II Marginal Zone Lymphoma
Stage II Small Lymphocytic Lymphoma
Extranodal Marginal Zone B-cell Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Adult Burkitt Lymphoma
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Splenic Marginal Zone Lymphoma
Stage I Adult Burkitt Lymphoma
Stage I Adult Diffuse Large Cell Lymphoma
Stage I Adult Hodgkin Lymphoma
Stage I Adult Lymphoblastic Lymphoma
Stage I Chronic Lymphocytic Leukemia
Stage I Grade 1 Follicular Lymphoma
Stage I Grade 2 Follicular Lymphoma
Stage I Small Lymphocytic Lymphoma
Stage II Adult Hodgkin Lymphoma
Stage II Chronic Lymphocytic Leukemia
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Waldenström Macroglobulinemia
Interventions Drug: fenretinide
Drug: rituximab
Enrollment 32
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Fenretinide and Rituximab
Hide Arm/Group Description

PHASE I: Patients receive fenretinide PO BID on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.

pharmacological study : Correlative studies

rituximab : Given IV

fenretinide : Given PO

Period Title: Overall Study
Started 32
Completed 32
Not Completed 0
Arm/Group Title Fenretinide and Rituximab
Hide Arm/Group Description

PHASE I: Patients receive fenretinide PO BID on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.

pharmacological study : Correlative studies

rituximab : Given IV

fenretinide : Given PO

Overall Number of Baseline Participants 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
<=18 years
0
   0.0%
Between 18 and 65 years
19
  59.4%
>=65 years
13
  40.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants
62  (10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Female
6
  18.8%
Male
26
  81.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 32 participants
32
1.Primary Outcome
Title Safety, in Terms of Dose-limiting Toxicity (DLT) of 2 Daily Doses of Single Agent Fenretinide (Phase I)
Hide Description

A group of 3 patients would start treatment ast the dose of 900mg/m^2 BID, and if none of the 3 experienced a DLT, another 3 would then be treated at that dose. Dose Limiting Toxicity was defined as any related toxicity of grade 4 or 5 on or before the completion of 4 weeks of therapy.

Per response evaluation criteria 1999 Cheson Response Criteria for Malignant Lymphoma (CHESON99) for target lesions assessed by either CT or MRI:

Complete Response (CR): Complete disappearance of all measurable and non-measurable disease; Complete Response Unconfirmed (CRU): Complete disappearance of all measurable and non-measurable disease, with the exception of all residual nodal masses >1.5cm in Greatest Transverse Diameter (GTD) reduced by 75% in Sum of the Product of the greatest Diameters (SPD); Partial Response (PR): 50% decrease in the SPD.

Time Frame Number of participants that experienced a dose-limiting toxicity
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
7 participants were analyzed in the Rituximab Naive arm and 16 participants were analyzed in the Rituximab Pre Treated Arm.
Arm/Group Title Fenretinide and Rituximab
Hide Arm/Group Description:

PHASE I: Patients receive fenretinide PO BID on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.

pharmacological study : Correlative studies

rituximab : Given IV

fenretinide : Given PO

Overall Number of Participants Analyzed 23
Measure Type: Number
Unit of Measure: participants
0
2.Primary Outcome
Title Response Rates of B-Non-Hodgkin Lymphoma to the Combination of Rituximab and Fenretinide (Phase II)
Hide Description The trial was stratified into rituximab-naïve and rituximab pre-treated patients, and the target response rates for these groups were expected to be 30% and 10%, respectively. The numbers reported below are subjects who achieved a response of partial response or better.
Time Frame Up to 7 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
No subjects in Phase 1 met the DLT, therefore Phase II was conducted at 900mg/m2. Of the 32 subjects, 4 subjects were not evaluable for disease response (2 subjects in Phase 1 and 2 subjects in Phase 2).
Arm/Group Title Fenretinide and Rituximab (Rituximab Naive) Fenretinide and Rituximab (Rituximab Pre Treated)
Hide Arm/Group Description:
PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8.
PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8.
Overall Number of Participants Analyzed 7 16
Measure Type: Number
Unit of Measure: participants
4 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Fenretinide and Rituximab
Hide Arm/Group Description

PHASE I: Patients receive fenretinide PO BID on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.

pharmacological study : Correlative studies

rituximab : Given IV

fenretinide : Given PO

All-Cause Mortality
Fenretinide and Rituximab
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Fenretinide and Rituximab
Affected / at Risk (%) # Events
Total   6/32 (18.75%)    
Cardiac disorders   
Acute Coronary Syndrome * 5  1/32 (3.13%)  1
Immune system disorders   
Allergic Reaction * 1  1/32 (3.13%)  1
Infections and infestations   
Infections and infestations - Other, specify, Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10 * 4  1/32 (3.13%)  1
Wound Infection * 6  1/32 (3.13%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify, Papillary Thy * 8  1/32 (3.13%)  1
Skin and subcutaneous tissue disorders   
Rash Maculo-papular * 3  1/32 (3.13%)  1
Pruritus * 7  1/32 (3.13%)  1
Vascular disorders   
Hypotension * 2  1/32 (3.13%)  1
*
Indicates events were collected by non-systematic assessment
1
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2
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3
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4
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5
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6
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7
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8
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Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Fenretinide and Rituximab
Affected / at Risk (%) # Events
Total   32/32 (100.00%)    
Blood and lymphatic system disorders   
Anemia *  10/32 (31.25%)  22
Bone marrow hypocellular *  5/32 (15.63%)  11
Febrile Neutropenia *  2/32 (6.25%)  2
Eye disorders   
Night Blindness * 1  18/32 (56.25%)  53
Blurred Vision *  4/32 (12.50%)  7
Cataract *  3/32 (9.38%)  8
Dry Eye *  5/32 (15.63%)  7
Eye disorders - Other, specify, yellowing/discoloration of lights *  15/32 (46.88%)  17
Eye disorders - Other, specify, Altered color perception *  4/32 (12.50%)  13
Flashing Lights *  4/32 (12.50%)  4
Gastrointestinal disorders   
Abdominal Distention *  2/32 (6.25%)  3
Abdominal Pain *  7/32 (21.88%)  16
Constipation *  6/32 (18.75%)  7
Diarrhea *  12/32 (37.50%)  20
Flatulance *  3/32 (9.38%)  4
Nausea *  3/32 (9.38%)  4
General disorders   
Chills *  2/32 (6.25%)  2
Edema Limbs *  6/32 (18.75%)  9
Fatigue *  11/32 (34.38%)  33
Fever *  2/32 (6.25%)  2
Pain *  2/32 (6.25%)  2
Immune system disorders   
Allergic Reaction *  3/32 (9.38%)  3
Cytokine release syndrome *  7/32 (21.88%)  18
Infections and infestations   
Sinusitis *  4/32 (12.50%)  4
Upper Respiratory Infection *  4/32 (12.50%)  4
Urinary Tract Infection *  2/32 (6.25%)  3
Vaginal Infection *  2/32 (6.25%)  3
Injury, poisoning and procedural complications   
Bruising *  2/32 (6.25%)  3
Fracture *  4/32 (12.50%)  6
Investigations   
Alanine aminotransferase increased *  3/32 (9.38%)  3
Alkaline phosphatase increased *  2/32 (6.25%)  3
Aspartate aminotransferase increased *  5/32 (15.63%)  8
Blood Bilirubin Increased *  5/32 (15.63%)  7
Cholesterol High *  2/32 (6.25%)  2
Creatinine Increased *  7/32 (21.88%)  22
Lymphocyte Count Decreased *  9/32 (28.13%)  31
Neutrophil Count Decreased *  9/32 (28.13%)  16
Platelet Count Decreased *  10/32 (31.25%)  29
White Blood Cell Decreased *  9/32 (28.13%)  27
Metabolism and nutrition disorders   
Anorexia *  7/32 (21.88%)  7
Hyperglycemia *  5/32 (15.63%)  16
Hypernatremia *  2/32 (6.25%)  2
Hypoalbuminemia *  11/32 (34.38%)  21
Hypocalcemia *  16/32 (50.00%)  31
Hypokalemia *  5/32 (15.63%)  12
Hyponatremia *  6/32 (18.75%)  7
Musculoskeletal and connective tissue disorders   
Arthralgia *  4/32 (12.50%)  4
Bone Pain *  3/32 (9.38%)  5
Myalgia *  4/32 (12.50%)  5
Pain in Extremity *  2/32 (6.25%)  2
Nervous system disorders   
Dizziness *  7/32 (21.88%)  7
Peripheral Sensory Neuropathy *  6/32 (18.75%)  8
Psychiatric disorders   
Anxiety *  2/32 (6.25%)  4
Depression *  3/32 (9.38%)  3
Insomnia *  5/32 (15.63%)  5
Renal and urinary disorders   
Urinary Frequency *  3/32 (9.38%)  4
Respiratory, thoracic and mediastinal disorders   
Atelectasis *  2/32 (6.25%)  3
Cough *  4/32 (12.50%)  8
Dyspnea *  4/32 (12.50%)  5
Pharyngolaryngeal Pain *  3/32 (9.38%)  3
Skin and subcutaneous tissue disorders   
Alopecia *  2/32 (6.25%)  2
Dry Skin *  9/32 (28.13%)  10
Hyperhidrosis *  4/32 (12.50%)  5
Photosensitivity *  9/32 (28.13%)  20
Pruritus *  2/32 (6.25%)  5
Rash maculo-papular *  20/32 (62.50%)  22
Vascular disorders   
Hot Flashes *  6/32 (18.75%)  6
Hypotension *  3/32 (9.38%)  3
Thromboembolic Event *  2/32 (6.25%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, 10029404
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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. Ajay Gopal
Organization: University of Washington
Phone: 206-288-2035
EMail: agopal@uw.edu
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00288067     History of Changes
Other Study ID Numbers: NCI-2009-00104
NCI-2009-00104 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000456502 ( Other Identifier: NCI )
UWCC-UW-6071 ( Other Identifier: Fred Hutchinson Cancer Research Center )
UWCC-06-0644-H/A ( Other Identifier: Fred Hutchinson Cancer Research Center )
UWCC-6071 ( Other Identifier: Fred Hutchinson Cancer Research Center )
FHCRC-6071 ( Other Identifier: Fred Hutchinson Cancer Research Center )
6071 ( Other Identifier: University of Washington Medical Center )
6957 ( Other Identifier: CTEP )
R21CA119519 ( U.S. NIH Grant/Contract )
First Submitted: February 6, 2006
First Posted: February 7, 2006
Results First Submitted: January 8, 2014
Results First Posted: October 6, 2014
Last Update Posted: October 6, 2014