|- candidate number||8086|
|- NTR Number||NTR2338|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||25-mei-2010|
|- Secondary IDs||2010/079 MEtC VUmc|
|- Public Title||Zevalin-BEAM or Zevalin as consolidation in patients with transformed lymphoma.|
|- Scientific Title||Zevalin (90Yttrium-ibritumomab tiuxetan)-BEAM and autologous stem cell transplantation or single dose 90Yttrium ibritumomab tiuxetan as consolidation of induction chemotherapy in patients with transformed non-Hodgkin’s lymphoma. A phase II clinical trial.
|- hypothesis||Consolidation of first line treatment of patients with transformed lymphoma with Zevalin of Zevalin-BEAM will prolong PFS.|
|- Healt Condition(s) or Problem(s) studied||Non Hodkin's lymfoma (NHL)|
|- Inclusion criteria||1. First diagnosis of transformation of lymphoma;|
2. Histologically confirmed CD20 positive transformed B cell NHL lymphoma, according to the WHO classification 2008, stage I-IV;
3. For consolidation with AuSCT after Z-BEAM: age 18-66 years old;
4. For single dose 90Y-ibritumomab tiuxetan: older than 65 years and 18-66 years but ineligible for autologous stem cell transplantation;
5. WHO performance status of 0-2 (Appendix C);
6. Life expectancy of at least 3 months;
7. Induction treatment with R-CHOP or R-DHAP-VIM-DHAP;
8. CR defined as disappearance of all evidence of disease on PET-CT or PR defined as a reduction of tumor size of more than 50% and decreasing FDG-avidity on PET-CT after induction consisting of rituximab containing polychemotherapy. (see appendix A);
9. Absense of PET positive bulky disease after induction treatment defined as a lesion larger than 5 cm;
10. Less than 25% bone marrow involvement at the end of induction treatment (measurement in a representative bone marrow biopsy);
11. For AuSCT: Stem cells harvested: a minimum of 2 x 106 CD34+ cells/kg;
12. For single dose 90Y-ibritumomab tiuxetan: ANC ≥ 1.5 x 109/l and platelets ≥ 100 x 109/l;
13. Written informed consent obtained according to local guidelines.
|- Exclusion criteria||1. Known hypersensitivity to murine antibodies or proteins;|
2. Presence of any other active neoplasms or history of prior malignancy, except non-melanoma skin tumours or stage 0 (in situ) cervical carcinoma during the past 5 years;
3. Patients with abnormal liver function (total bilirubin > 2.0 x ULN);
4. Presence of CNS involvement;
5. Patients with pleural effusion or ascites after induction therapy;
6. Patients who have received G-CSF or GM-CSF therapy within two weeks prior to study enrollment;
7. Patients who have received biologic therapy, immunotherapy, R-CHOP(-like) chemotherapy, surgery, or an investigational drugs less than 4 weeks prior to first day of study treatment (i.e. 90Yttrium ibritumomab tiuxetan + AuSCT) or who have not recovered from the toxic effects of such therapy;
8. Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control during study treatment and for at least 12 months thereafter;
9. Known diagnosis of HIV infection;
10. Patients unwilling or unable to comply with the protocol.
Additional exclusion criteria for autologous SCT:
Unfit for high dose chemotherapy followed by autologous stem cell transplantation due to physical or mental condition.
Additional exclusion criteria for single dose 90Y-ibritumomab tiuxetan:
Patients who have received prior external beam radiotherapy to > 25% of active bone marrow (involved field or regional).
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, non-randomized|
|- planned startdate ||1-jun-2010|
|- planned closingdate||1-mei-2014|
|- Target number of participants||58|
|- Interventions||1. Consolidation of induction chemotherapy in patients eligible for stem cell transplantation with AuSCT preceeded by Zevalin-BEAM conditioning;|
2. When autologous stem cell transplant is not feasible due to age, comorbidity and/or physical fitness, consolidation of induction chemotherapy in patients with transformed lymphoma not eligible for stem cell transplantation with a single dose (0,4 mCi/kg, max 32 mCi) of 90Y ibritumomab tiuxetan in order to prevent recurrence and prolong PFS.
|- Primary outcome||2-year PFS in patients with transformed non-Hodgkin’s lymphoma in CR or PR after induction chemotherapy consolidated by 90Yttrium-ibritumomab tiuxetan followed by BEAM and autologous stem cell transplantation or, in patients not eligible for AuSCT, consolidated by a single dose of 90Yttrium-ibritumomab tiuxetan.|
|- Secondary outcome||1. 2-year OS;|
2. Time to next treatment (TTNT);
3. Toxicity in terms of time to recovery of neutrophils and platelets related to previous treatment for indolent or transformed lymphoma;
4. Conversion rate to CR assessed by PET-CT scan after 90Yttrium-ibritumomab tiuxetan (if eligible followed by BEAM and autologous stem cell transplantation) in patients with transformed non-Hodgkin’s lymphoma in PET positive PR before consolidation;
5. Reconstitution of immunoglobins and B- and T-cell subsets and NK-cells at different time points after treatment with 90Yttrium-ibritumomab tiuxetan (with or without AuSCT) and monitor the incidence of infections.
|- Timepoints||End point is progression free survival after 2 years.|
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| M.J. Wondergem|
|- CONTACT for SCIENTIFIC QUERIES|| M.J. Wondergem|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|VU University Medical Center|
|- Brief summary||Study phase: |
Phase II clinical trial.
To estimate 2 year PFS in patients with transformed NHL after consolidation with 90Y ibritumomab tiuxetan-BEAM and AuSCT in patients eligible for AuSCT or after consolidation with a single dose of 90Y ibritumomab tiuxetan in patients not eligible for AuSCT.
Patients with transformed non-Hodgkin’s lymphoma in CR or PR after induction/salvage chemotherapy.
Phase II prospective cohort study, single center, open label, non-randomized.
Duration of treatment:
Within 3 months of reaching PR or CR after induction therapy, 90Y ibritumomab tiuxetan should be administered, in case of AuSCT followed a week later by BEAM and stem cell transplantation. PET-CT for remission-assessment is done three months and two years after single dose 90Y ibritumomab tiuxetan or AuSCT.
Number of patients:
Z-BEAM followed by AuSCT: 29
90Y ibritumomab tiuxetan single dose: 29.
1. Length of recovery of neutophils and platelets;
2. Immune reconstitution.
Start of recruitment: 01-05-2010;
End of recruitment: 01-05-2014.
|- Main changes (audit trail)|
|- RECORD||25-mei-2010 - 5-jun-2010|