Non-Hodgkin's Lymphoma
Conditions
Keywords
non-Hodgkin's lymphoma, autologous stem cell transplantation, radioimmunotherapy, zevalin
Brief summary
The study hypothesis is that the addition of zevalin radioimmunotherapy to the conditioning regimen given prior to BEAM high-dose chemotherapy and autologous stem cell transplantation in patients with aggressive lymphoma will reduced disease recurrence rate and improve overall and disease-free survival.
Interventions
0.4 mCi/kg
PROCEDUREBEAM chemotherapy and autologous stem-cell transplantation
Sponsors
City of Hope Medical Center
Amsterdam UMC, location VUmc
University of Göttingen
Sheba Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with CD20 positive diffuse large B-cell lymphoma as confirmed by a pathological biopsy report. 2. Patients who are candidates for autologous stem-cell transplantation due to primary refractory or first relapse of disease. 3. Patients must have chemo-sensitive disease achieving at least partial response (Cheson 2007 criteria) to last chemotherapy. 4. Age ≥ 18 years and age ≤ 70 5. Patients with adequate autologous stem cell collection for transplantation (target ≥ 2.5 x 106 CD34+ cells/kg). 6. Patients must sign written informed consent. 7. Adequate birth control in fertile patients. 8. All prior chemotherapy completed at least three weeks before study treatment. 9. Marrow involvement less than 25% at transplantation, no limitation on blood counts (low platelet count allowed). 10. Negative HIV antibody.
Exclusion criteria
1. 1\. Chemo-refractory disease as determined by less than partial response (Cheson 2007 Criteria) to last chemotherapy. 2. Two or more relapses after initial response to induction chemotherapy. 3. High-grade transformation from earlier diagnosis of low-grade lymphoma. Patients with De Novo Transformed DLBCL, defined as DLBCL only on lymph node biopsy and a discordant marrow with para-trabecular small cells at first diagnosis of lymphoma, are eligible if adherent all other selection criteria. 4. Bilirubin \> 3.0 mg/dl, transaminases \> 3 times upper normal limit. 5. Creatinine \> 2.0 mg/dl. 6. ECOG Performance status \> 2. 7. Uncontrolled infection. 8. Pregnancy or lactation. 9. Abnormal lung diffusion capacity (DLCO \< 40% predicted). 10. Severe cardiovascular disease; New York Heart Association (NYHA) Functional Classification ≥2. 11. Active CNS disease involvement. 12. Presence of any other malignancy or history of prior malignancy within 5 years of study entry. Within 5 years, patients treated for Stage I or II cancers are eligible provided they have a life expectancy \> 5 years in relation to this prior malignance. The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ cervical cancer. 13. Pleural effusion or ascites \> 1 liter. 14. Known hypersensitivity to rituximab. 15. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate. 16. Prior radioimmunotherapy. 17. Prior autologous or allogeneic HSCT. 18. Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive. 19. Patients who have had prior radiation to the lung will be excluded from the study, although mediastinal irradiation will be permitted if minimal lung is in the treatment volume. 20. Patients who have received \>500cGy radiation to the kidneys will be excluded from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 2 years after transplantation | actuarial 2 year survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 2 years after transplantation | actuarial 2-year PFS |
| Clinical Response | 100 days after transplantation | complete response (CR) and partial response (PR) proportion at day 100, |
| Hematopoietic Recovery | 100 days after transplantation | time to hematopoietic recovery |
| Grade III Toxicity | 100 days after transplantation | incidence of infection, grade III-IV toxicities, treatment-related mortality |
| Secondary Malignancies | 5 years after transplantation | incidence of myelodysplastic syndrome (MDS), and secondary acute myelogenous leukemia (AML). |
Countries
Germany, Israel, Netherlands, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Z-BEAM ibritumomab tiuxetan (zevalin) BEAM
ibritumomab tiuxetan: 0.4 mCi/kg
BEAM chemotherapy and autologous stem-cell transplantation | 22 |
| Standard BEAM standard BEAM chemotherapy
BEAM chemotherapy and autologous stem-cell transplantation | 21 |
| Total | 43 |
Baseline characteristics
| Characteristic | Z-BEAM | Standard BEAM | Total | — |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | — |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants | — |
| Age, Categorical Between 18 and 65 years | 21 Participants | 20 Participants | 41 Participants | — |
| Age, Continuous | 58 years | 51 years | 55 years | — |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment Germany | — | — | — | — participants |
| Region of Enrollment Israel | 22 participants | 21 participants | 43 participants | — |
| Region of Enrollment Netherlands | — | — | — | — participants |
| Region of Enrollment United States | — | — | — | — participants |
| Sex: Female, Male Female | 16 Participants | 11 Participants | 27 Participants | — |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 16 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 22 | 1 / 21 |
| serious Total, serious adverse events | 1 / 22 | 0 / 21 |
Outcome results
Primary
Overall Survival
actuarial 2 year survival
Time frame: 2 years after transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Z-BEAM | Overall Survival | 91 percentage of participants |
| Standard BEAM | Overall Survival | 62 percentage of participants |
Secondary
Clinical Response
complete response (CR) and partial response (PR) proportion at day 100,
Time frame: 100 days after transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Z-BEAM | Clinical Response | 22 participants |
| Standard BEAM | Clinical Response | 20 participants |
Secondary
Grade III Toxicity
incidence of infection, grade III-IV toxicities, treatment-related mortality
Time frame: 100 days after transplantation
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Z-BEAM | Grade III Toxicity | infection | 6 Participants |
| Z-BEAM | Grade III Toxicity | none | 13 Participants |
| Z-BEAM | Grade III Toxicity | grade III toxicity | 3 Participants |
| Standard BEAM | Grade III Toxicity | grade III toxicity | 4 Participants |
| Standard BEAM | Grade III Toxicity | infection | 1 Participants |
| Standard BEAM | Grade III Toxicity | none | 16 Participants |
Secondary
Hematopoietic Recovery
time to hematopoietic recovery
Time frame: 100 days after transplantation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Z-BEAM | Hematopoietic Recovery | 10 DAYS |
| Standard BEAM | Hematopoietic Recovery | 11 DAYS |
Secondary
Progression-free Survival
actuarial 2-year PFS
Time frame: 2 years after transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Z-BEAM | Progression-free Survival | 59 percentage of PARTICIPANTS |
| Standard BEAM | Progression-free Survival | 37 percentage of PARTICIPANTS |
Secondary
Secondary Malignancies
incidence of myelodysplastic syndrome (MDS), and secondary acute myelogenous leukemia (AML).
Time frame: 5 years after transplantation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Z-BEAM | Secondary Malignancies | 0 Participants |
| Standard BEAM | Secondary Malignancies | 0 Participants |