Fludarabine, Velcade and Rituximab for Relapsed or Refractory Follicular Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the effectiveness of fludarabine, Velcade, and rituximab treatment regimen in patients with relapsed or refractory follicular non-Hodgkin lymphoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
OUTLINE: This is a multi-center study.
-
Fludarabine 25 mg/m2 IV over 30 minutes , Days 1, 2, 4
-
Velcade(given after fludarabine) 1.3 mg/m2 IV push over 3 to 5 seconds, Days 1, 4, 8, 11
-
Rituximab (given after Velcade) 375 mg/m2 IV piggyback, Day 1
-
Cycle = 28 days; max 6 cycles
ECOG Performance Status: 0-2
Life Expectancy: Not specified
Hematopoietic:
-
Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 (ANC > 0.5 K/mm3 if known lymphomatous involvement of the bone marrow).
-
Platelets ≥ 100 K/mm3 (Platelets >50 K/mm3 if known lymphomatous involvement of the bone marrow).
Hepatic:
-
Total bilirubin ≤1.5 ULN
-
Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN
-
Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN
Renal:
- Creatinine < 1.5 x institutional upper limit (ULN) or creatinine clearance ≥ 50 cc/min
Cardiovascular:
-
No myocardial infarction within 6 months prior to enrollment
-
No heart failure per New York Heart Association Classification III or IV
-
No severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Fludarabine, Velcade and Rituximab Fludarabine, Velcade and Rituximab |
Drug: Fludarabine
Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy.
Drug: Velcade
Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy.
Drug: Rituximab
Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy.
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate [6 months]
To determine the overall response rate and frequency of complete and partial responses in patients with relapsed or refractory follicular non-Hodgkin lymphoma (NHL) who receive therapy with fludarabine, Velcade, and rituximab administered every 28 days.
Secondary Outcome Measures
- Survival [6 months]
To evaluate the progression-free survival and event-free survival in patients who receive therapy with fludarabine, Velcade, and rituximab.
- Toxicity [6 months]
To evaluate the toxicity profile of this regimen. Adverse event counts by grade are presented.
- Biologic Interaction [6 months]
To explore the biologic interaction between fludarabine and Velcade and determine if Velcade can potentiate the DNA-damaging effect of fludarabine.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Must have histologically confirmed Follicular Non-Hodgkin Lymphoma (Grade I, II, or IIIa)
-
Must have measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥2 cm with conventional techniques or as >1 cm with spiral CT scan) and obtained by imaging within 30 days prior to registration for protocol therapy.
-
Must have received at least one prior therapeutic regimen, but no more than three prior regimens of conventional cytotoxic therapy. NOTE: Prior recipients of stem cell transplantation will be included, with the preparative cytoreductive and high-dose therapies counted collectively as one prior therapy.
-
Must be off all cytotoxic chemotherapy for at least four weeks prior to registration for protocol therapy (6 weeks for BCNU or mitomycin C).
-
Patients are allowed to have received one course of prior radioimmunotherapy (RIT: either tositumomab or ibritumomab). NOTE: Radioimmunotherapy must be completed at least 12 weeks prior to registration for protocol therapy with recovery to baseline of ANC and platelets.
-
Prior fludarabine, Velcade or rituximab is allowed as long as therapy is completed at least 30 days prior to registration for protocol therapy. Patients may be refractory (defined as not responding or demonstrating progressive disease in <6 months) to prior rituximab. Patients may not be refractory to prior fludarabine or Velcade.
-
Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed and for 30 days following protocol therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
-
Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to prior to registration for protocol therapy. NOTE: Patients are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (no menses for at least 12 months).
-
Females must not be breastfeeding.
-
Males must agree to use an acceptable method of contraception for the duration of the study.
Exclusion Criteria:
-
No current active CNS metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis within 7 days prior to registration for protocol therapy. NOTE: Patients with treated brain metastasis must be off steroids or on tapering or stable doses of steroids and have completed radiation at least 30 days prior to registration for protocol therapy.
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No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason ≤ grade 6 prostate cancers, or other cancer for which the subject has been disease-free for at least 3 years.
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No treatment with any investigational agent within 30 days prior to registration for protocol therapy.
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Prior radiation therapy is allowed to < 25% of the bone marrow. NOTE: No radiation therapy within 30 days prior to registration for protocol therapy.
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No clinically significant infections as judged by the treating investigator.
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No active HIV, hepatitis B or hepatitic C infection.
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No cerebrovascular accident (CVA) within 6 months of study enrollment.
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No psychiatric illness/social situations that would limit compliance with study requirements.
-
No history of hypersensitivity to Velcade, boron or mannitol.
-
No peripheral neuropathy grade > 1.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cancer Care Center of Southern Indiana | Bloomington | Indiana | United States | 47403 |
| 2 | Fort Wayne Oncology & Hematology, Inc | Fort Wayne | Indiana | United States | 46815 |
| 3 | Indiana University Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | United States | 46202 |
| 4 | Community Regional Cancer Center | Indianapolis | Indiana | United States | 46256 |
| 5 | Arnett Cancer Care | Lafayette | Indiana | United States | 47904 |
| 6 | Virtua Health Cancer Program | Mount Holly | New Jersey | United States | 08060 |
| 7 | South Jersey Health Care | Vineland | New Jersey | United States | 08360 |
| 8 | University of Rochester Medical Center | Rochester | New York | United States | 14642 |
| 9 | Case Comprehensive Cancer Center - University Hospitals Case Medical Center | Cleveland | Ohio | United States | 44106 |
| 10 | Seidman Cancer Center | Cleveland | Ohio | United States | 44106 |
| 11 | Reading Hospital Regional Cancer Center | W. Reading | Pennsylvania | United States | 19611 |
Sponsors and Collaborators
- Hoosier Cancer Research Network
- Genentech, Inc.
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Chair: Shivani Srivastava, M.D., Hoosier Cancer Research Network
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- HOG LYM08-134
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Fludarabine, Velcade and Rituximab |
|---|---|
| Arm/Group Description | Fludarabine, Velcade and Rituximab Fludarabine: Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy. Velcade: Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy. Rituximab: Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy. |
| Period Title: Overall Study | |
| STARTED | 4 |
| COMPLETED | 3 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Fludarabine, Velcade and Rituximab |
|---|---|
| Arm/Group Description | Fludarabine, Velcade and Rituximab Fludarabine: Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy. Velcade: Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy. Rituximab: Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy. |
| Overall Participants | 4 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
59.50
(14.01)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
25%
|
| Male |
3
75%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
4
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
4
100%
|
Outcome Measures
| Title | Overall Response Rate |
|---|---|
| Description | To determine the overall response rate and frequency of complete and partial responses in patients with relapsed or refractory follicular non-Hodgkin lymphoma (NHL) who receive therapy with fludarabine, Velcade, and rituximab administered every 28 days. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for this primary objective was not collected or analyzed due to the termination of the study. |
| Arm/Group Title | Fludarabine, Velcade and Rituximab |
|---|---|
| Arm/Group Description | Fludarabine, Velcade and Rituximab Fludarabine: Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy. Velcade: Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy. Rituximab: Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy. |
| Measure Participants | 0 |
| Title | Survival |
|---|---|
| Description | To evaluate the progression-free survival and event-free survival in patients who receive therapy with fludarabine, Velcade, and rituximab. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for this secondary objective was not collected or analyzed due to the termination of the study. |
| Arm/Group Title | Fludarabine, Velcade and Rituximab |
|---|---|
| Arm/Group Description | Fludarabine, Velcade and Rituximab Fludarabine: Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy. Velcade: Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy. Rituximab: Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy. |
| Measure Participants | 0 |
| Title | Toxicity |
|---|---|
| Description | To evaluate the toxicity profile of this regimen. Adverse event counts by grade are presented. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Fludarabine, Velcade and Rituximab |
|---|---|
| Arm/Group Description | Fludarabine, Velcade and Rituximab Fludarabine: Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy. Velcade: Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy. Rituximab: Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy. |
| Measure Participants | 4 |
| Total Adverse Events |
122
|
| Grade 1 Adverse Events |
77
|
| Grade 2 Adverse Events |
35
|
| Grade 3 Adverse Events |
9
|
| Grade 4 Adverse Events |
1
|
| Grade 5 Adverse Events |
0
|
| Title | Biologic Interaction |
|---|---|
| Description | To explore the biologic interaction between fludarabine and Velcade and determine if Velcade can potentiate the DNA-damaging effect of fludarabine. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for this secondary objective was not collected or analyzed due to the termination of the study. |
| Arm/Group Title | Fludarabine, Velcade and Rituximab |
|---|---|
| Arm/Group Description | Fludarabine, Velcade and Rituximab Fludarabine: Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy. Velcade: Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy. Rituximab: Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | 6 months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Fludarabine, Velcade and Rituximab | |
| Arm/Group Description | Fludarabine, Velcade and Rituximab Fludarabine: Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy. Velcade: Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy. Rituximab: Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy. | |
All Cause Mortality |
||
| Fludarabine, Velcade and Rituximab | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Fludarabine, Velcade and Rituximab | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/4 (25%) | |
| Blood and lymphatic system disorders | ||
| BLOOD/BONE MARROW - OTHER (SPECIFY, __) | 1/4 (25%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Fludarabine, Velcade and Rituximab | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | |
| Blood and lymphatic system disorders | ||
| HEMOGLOBIN | 3/4 (75%) | 6 |
| LEUKOCYTES (TOTAL WBC) | 1/4 (25%) | 1 |
| LYMPHOPENIA | 1/4 (25%) | 7 |
| NEUTROPHILS/GRANULOCYTES (ANC/AGC) | 1/4 (25%) | 4 |
| PAIN / LYMPH NODE | 1/4 (25%) | 1 |
| PLATELETS | 3/4 (75%) | 6 |
| Cardiac disorders | ||
| HYPERTENSION | 1/4 (25%) | 1 |
| Eye disorders | ||
| NYSTAGMUS | 1/4 (25%) | 1 |
| WATERY EYE (EPIPHORA, TEARING) | 1/4 (25%) | 1 |
| Gastrointestinal disorders | ||
| ANOREXIA | 1/4 (25%) | 2 |
| CONSTIPATION | 3/4 (75%) | 12 |
| GASTRITIS (INCLUDING BILE REFLUX GASTRITIS) | 1/4 (25%) | 1 |
| NAUSEA | 2/4 (50%) | 8 |
| PAIN / ABDOMEN NOS | 1/4 (25%) | 1 |
| General disorders | ||
| CONSTITUTIONAL SYMPTOMS | 1/4 (25%) | 1 |
| FATIGUE (ASTHENIA, LETHARGY, MALAISE) | 4/4 (100%) | 14 |
| FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L) | 1/4 (25%) | 1 |
| PAIN / BACK | 1/4 (25%) | 1 |
| PAIN / HEAD/HEADACHE | 1/4 (25%) | 2 |
| PAIN - OTHER | 1/4 (25%) | 1 |
| RIGORS/CHILLS | 2/4 (50%) | 4 |
| SWEATING (DIAPHORESIS) | 1/4 (25%) | 1 |
| Immune system disorders | ||
| ALLERGIC REACTION/HYPERSENSITIVITY (INCLUDING DRUG FEVER) | 1/4 (25%) | 1 |
| Infections and infestations | ||
| INFECTION - OTHER | 1/4 (25%) | 1 |
| INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / UPPER AERODIGESTIVE NOS | 1/4 (25%) | 1 |
| Investigations | ||
| ALT, SGPT (SERUM GLUTAMIC PYRUVIC TRANSAMINASE) | 1/4 (25%) | 1 |
| AST, SGOT(SERUM GLUTAMIC OXALOACETIC TRANSAMINASE) | 1/4 (25%) | 1 |
| CREATININE | 1/4 (25%) | 3 |
| MAGNESIUM, SERUM-HIGH (HYPERMAGNESEMIA) | 1/4 (25%) | 2 |
| Musculoskeletal and connective tissue disorders | ||
| PAIN / EXTREMITY-LIMB | 1/4 (25%) | 2 |
| PAIN / JOINT | 1/4 (25%) | 2 |
| Nervous system disorders | ||
| ATAXIA (INCOORDINATION) | 1/4 (25%) | 1 |
| LEUKOENCEPHALOPATHY (RADIOGRAPHIC FINDINGS) | 1/4 (25%) | 1 |
| NEUROPATHY: MOTOR | 1/4 (25%) | 1 |
| NEUROPATHY: SENSORY | 2/4 (50%) | 10 |
| Psychiatric disorders | ||
| MOOD ALTERATION / AGITATION | 1/4 (25%) | 1 |
| MOOD ALTERATION / ANXIETY | 2/4 (50%) | 2 |
| Reproductive system and breast disorders | ||
| SEXUAL/REPRODUCTIVE FUNCTION - OTHER | 1/4 (25%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| COUGH | 1/4 (25%) | 1 |
| DYSPNEA (SHORTNESS OF BREATH) | 3/4 (75%) | 6 |
| HICCOUGHS (HICCUPS, SINGULTUS) | 1/4 (25%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| BRUISING (IN ABSENCE OF GRADE 3 OR 4 THROMBOCYTOPENIA) | 1/4 (25%) | 1 |
| HAIR LOSS/ALOPECIA (SCALP OR BODY) | 2/4 (50%) | 3 |
| Surgical and medical procedures | ||
| MUCOSITIS/STOMATITIS (CLINICAL EXAM) / ORAL CAVITY | 1/4 (25%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT 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 | Clinical Data Coordinator |
|---|---|
| Organization | Hoosier Cancer Research Network, Inc. |
| Phone | 317-921-2050 |
| jsmith@hoosiercancer.org |
- HOG LYM08-134