Lymphoma, B-Cell
Conditions
Keywords
high risk non-hodgkins lymphoma, NHL, Bexxar, high dose chemotherapy
Brief summary
The purpose of this study is to determine whether using high-dose chemotherapy, monoclonal antibodies, and targeted radioimmunotherapy will slow the progression of disease in patients with high-risk Non-Hodgkin's Lymphoma (NHL).
Detailed description
This is a phase II efficacy trial for patients with untreated, high-risk, B-cell Non-Hodgkin's Lymphoma. The study will evaluate the efficacy and safety of high-dose chemotherapy combined with monoclonal antibodies and targeted radioimmunotherapy in previously untreated patients with high-risk NHL
Interventions
DRUGcyclophosphamide
1.5g/m2 IV over 1 hour on days 1-4 of induction for a total dose of 6.0g/m2
DRUGetoposide
300mg/m2 IV over 1 hour every 12 on days 1-3 of induction for a total dose of 1.8 g/m2.
DRUGrituximab
375mg/m2 each week x 4 weeks of induction, beginning on day 1
DRUGcytarabine
3g/m2 IV over 1 hour every 12 during consolidation for a total of 8 doses
DRUGdoxorubicin
45mg/m2/day IV over 30 minutes on days 1, 2, 3 during consolidation
DRUGtositumomab
450mg unlabeled tositumomab over 1 hour, followed by 5 millicurie (mCi) Iodine I-131 labeled tositumomab over 20 minutes on day 0. Therapeutic dose of labeled tositumomab will be administered on day 15.
Sponsors
GlaxoSmithKline
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Untreated, biopsy proven B-cell non-Hodgkin's lymphoma * Age \>/= 18 years * No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for one year. The patient cannot have been exposed to chemotherapy to treat any of these diseases for at least 3 years prior to study entry. * Meet staging studies and laboratory tests prior to induction, consolidation and radioimmunotherapy.
Exclusion criteria
* Significant medical and/or psychiatric illness which may compromise planned treatment; * Pregnant or lactating; * HIV-infection. * Patients with follicular lymphoma grade 1, 2 or 3A are not eligible for this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1 Year Progression-free Survival Rate | 1 year | Progression-free survival is measured from the first day of induction chemotherapy to the date of progression, relapse or death. Definitions of response criteria are as described by Cheson. Progressive Disease: \>50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PDs or nonresponders, appearance of any new lesion during or at the end of therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival | 10 years | Disease-free survival is measured from the date of CR or CRu to date of relapse or death |
| Overall Survival | 10 years | Overall Survival is measured from the first day of chemotherapy until death from any cause. |
| Overall Response | up to 1 year | Percent of subjects who achieved a complete response (CR) or partial response (PR) any time during the treatment period. CR = complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR = 1. \>/= 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. 2. No increase should be observed in the size of other nodes, liver, or spleen. 3. Splenic and hepatic nodules must regress by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. 4. Except splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. 5. Patients who achieve a CR by the above criteria, but who have persistent morphologic bone marrow involvement will be considered partial responders. 6. No new sites of disease should be observed. |
| Secondary Malignancies | 10 years | The number of patients who develop secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited between September 2005 and March 2011 at Duke University Medical Center.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Induction:Cyclophosphamide, Etoposide, and Rituxan followed by Consolidation:Cytarabine and Doxorubicin followed by radioimmunotherapy:Bexxar | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Long Term Follow-Up | Death | 15 |
| Long Term Follow-Up | Lost to Follow-up | 5 |
| Long Term Follow-Up | Physician Decision | 1 |
| Long Term Follow-Up | Withdrawal by Subject | 4 |
| Treatment Period | Death | 1 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Age, Customized | 60 Years |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 39 |
| serious Total, serious adverse events | 28 / 39 |
Outcome results
Primary
1 Year Progression-free Survival Rate
Progression-free survival is measured from the first day of induction chemotherapy to the date of progression, relapse or death. Definitions of response criteria are as described by Cheson. Progressive Disease: \>50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PDs or nonresponders, appearance of any new lesion during or at the end of therapy.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Induction + Consolidation + Bexxar | 1 Year Progression-free Survival Rate | 0.74 percentage of participants |
Secondary
Disease-free Survival
Disease-free survival is measured from the date of CR or CRu to date of relapse or death
Time frame: 10 years
Population: Subjects who achieved a complete response. 9 patients experienced disease progression; 4 patients died.~4 patients were lost-to-follow-up and 11 patients are still living, so DFS was calculated using the last date of follow-up.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Experimental: Induction + Consolidation + Bexxar | Disease-free Survival | 54.10 months |
Secondary
Overall Response
Percent of subjects who achieved a complete response (CR) or partial response (PR) any time during the treatment period. CR = complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR = 1. \>/= 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. 2. No increase should be observed in the size of other nodes, liver, or spleen. 3. Splenic and hepatic nodules must regress by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. 4. Except splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. 5. Patients who achieve a CR by the above criteria, but who have persistent morphologic bone marrow involvement will be considered partial responders. 6. No new sites of disease should be observed.
Time frame: up to 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Induction + Consolidation + Bexxar | Overall Response | 92 percentage of participants |
Secondary
Overall Survival
Overall Survival is measured from the first day of chemotherapy until death from any cause.
Time frame: 10 years
Population: All subjects who received chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Induction + Consolidation + Bexxar | Overall Survival | 82 percentage of participants |
Secondary
Secondary Malignancies
The number of patients who develop secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes.
Time frame: 10 years
Population: All patients who received chemotherapy
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental: Induction + Consolidation + Bexxar | Secondary Malignancies | Myelodysplastic Syndrome (MDS) | 3 Participants |
| Experimental: Induction + Consolidation + Bexxar | Secondary Malignancies | Acute Myeloid Leukemia (AML) | 1 Participants |
| Experimental: Induction + Consolidation + Bexxar | Secondary Malignancies | Pancreatic Cancer | 1 Participants |
| Experimental: Induction + Consolidation + Bexxar | Secondary Malignancies | Hodgkins Lymphoma | 1 Participants |
| Experimental: Induction + Consolidation + Bexxar | Secondary Malignancies | Melanoma | 1 Participants |
| Experimental: Induction + Consolidation + Bexxar | Secondary Malignancies | Renal Cell Carcinoma | 1 Participants |