Primary Objectives- Determine the MTD of pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine in *fit' patients with rel aNHL of B- or T-cell phenotype.- Evaluate the ORR and PFS using the combination of pixantrone…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's unspecified histology
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Phase 2:
-Objective ORR in both *fit* and *frail* relapsed aNHL pts
Secondary outcome
Phase 2:
- Safety and tolerability of the combination of pixantrone,
rituximab, etoposide and bendamustine
- CRR
- DOR
- Progression-free survival (PFS)
- Overall survival (OS)
- Successful bridging to stem cell therapy (e.g. 2nd auto- and/or 1st allo-SCT)
or other cell therapy (e.g. chimeric antigen receptor [CAR]-T cell therapy)
Background summary
Patients with aggressive non-Hodgkin lymphoma (aNHL) relapsing after 1st line
therapy and too frail for platinum-based salvage therapy followed by autologous
stem cell transplant (ASCT), those primary refractory to platinum-based salvage
regimens or those experiencing a 2nd relapse after ASCT consolidation
represent an unmet clinical need. Thus, three clinically and biologically
distinct patient categories can be identified: frail, not transplant eligible
(group 1); fit, transplant eligible but refractory to salvage therapy (group 2)
and fit, transplant eligible, chemo-sensitive to salvage regimen and ASCT, but
relapsing after ASCT (group 3). Based on population-based data from the Danish
Lymphoma Registry, the 1-year survival expectation (from the time of relapse)
within the aforementioned 3 groups is 33%, 21% and 42%, respectively.
Pixantrone is an aza-anthracenadione recently approved in Europe for patients
with relapsed/refractory aNHL based on phase 3 data comparing pixantrone with
physician*s best choice. Etoposide, bendamustine and, in CD20 positive tumors,
rituximab were chosen as companion compounds due to available feasibility and
efficacy data in combination with pixantrone.
Study objective
Primary Objectives
- Determine the MTD of pixantrone, rituximab (only in CD20 positive tumors),
etoposide, and bendamustine in *fit' patients with rel aNHL of B- or T-cell
phenotype.
- Evaluate the ORR and PFS using the combination of pixantrone, rituximab (only
in CD20 positive tumors), etoposide, and bendamustine either at the identified
MTD (P[R]EBEN-fit) in *fit* patients or at the baseline dose level
(P[R]EBEN-frail) in *frail* patients with rel aNHL.
Secondary objectives
- Evaluate the CR, PR, duration of response, and OS using the combination of
pixantrone, rituximab (only in CD20 positive tumors), etoposide, and
bendamustine in patients with B- or T-cell NHL.
- Evaluate the safety and tolerability of combination therapy with pixantrone,
rituximab (only in CD20 positive tumors), etoposide, and bendamustine in
patients with aggressive B- or T-cell NHL.
-To perform molecular analyses at nucleic acid (DNA, RNA, microRNA) and protein
level to see if specific molecular features can predict responder versus
non-responder status.
Study design
A Phase 1/2 study of the combination of pixantrone, etoposide, bendamustine
and, in CD-20 positive tumors, rituximab in patients with relapsed aggressive
non-Hodgkin lymphomas of B- or T-cell phenotype.
Intervention
In phase 2 the treatment will depend on if the patient is either classified as
fit or frail.
Fit patients will be treated with the in the phase 1 part of the study
determined MTD of Pixantrone, Etoposide and Bendamustine. Frail patients will
be treated with the baseline regimen of Pixantrone, Etoposide and Bendamustine.
Study burden and risks
Patients with aggressive non-Hodgkin lymphoma (NHL) relapsing after 1st line
therapy and too frail for platinum-based salvage therapy followed by autologous
stem cell transplant (ASCT) represent an unmet clinical need. The PREBEN
regimen is a new combination of the chemotherapeutics pixantrone, bendamustine,
etoposide and rituximab. In a small pilot study the PREBEN regimen gave
promising results and was well tolerated in a heavily pretreated patient
population. The burden for the patient to participate into this study is not
different from the burden of a treatment outside this clinical trial, except
for 5 extra CT scans during follow-up. If the results that were found in the
pilot study are confirmed in this study then PREBEN could be the new standard
treatment for this patient group. Also PREBEN could serve as a backbone regimen
for the combination with new drugs. Lastly, some young patients might be
offered an allogeneic stem cell transplantation with curative intent.
Tage Hansens Gade 2
Aarhus C DK-8000
DK
Tage Hansens Gade 2
Aarhus C DK-8000
DK
Listed location countries
Age
Inclusion criteria
- Patients with a histologically confirmed relapse of an aggressive lymphoma of T- or B-cell phenotype (including follicular lymphoma grade 3b).;- Phase 1 + Phase 2 *fit* patients:
--Age 18-70 years at the time of inclusion
--ECOG performance score (PS) 0-1 at protocol entry
--Deemed *fit* by the treating physician
- Phase 2 *frail* patients:
--Age 71-85 years at the time of inclusion
and/or
--ECOG PS 2-3 at protocol entry
and/or
--Deemed *frail* by the treating physician;- At least 6 months response duration since last given course of treatment
- Estimated life expectancy of 3 months or longer
- Measurable disease
- Hemoglobin >= 8 g/dL (>=5 mmol/l) (can be post transfusion)
- Platelets >= 100 x 109/L; >= 75 x 109/L permitted if bone marrow involvement
- Absolute neutrophil count >= 1.5 x 109/L; >= 1.0 x 109/L permitted if documented bone marrow involvement
- Serum bilirubin <= 1.5 x upper limit of normal (ULN); patients with proven Gilbert*s syndrome (<= 5 x
ULN) may be enrolled.
- Serum glutamic-oxaloacetic transaminase (AST) and/or serum glutamic-pyruvic transaminase (ALT) <= 2.5 x ULN, or <= 5 x ULN if elevation is due to hepatic involvement by lymphoma
- Serum creatinine <= 2 x ULN
- Women of childbearing potential must use safe anticonception (e.g. contraceptive pills, intrauterine devices etc.) during the study and 12 months after the last administration of study drugs
- Male patients must use contraception for the duration of the study and 6 months after the last administration of study drugs if his partner is of childbearing potential
- Written informed consent
Exclusion criteria
- Patients with primary refractory disease (e.g. progressing under platinum-containing or similar salvage therapy) defined as < 6 months response duration from last given course of treatment.
- High-dose therapy with autologous stem cell rescue within the last 6 months prior to study entry.
- Following T-cell lymphoma entities:
--T-cell lymphoblastic lymphoma
--Hepatosplenic T-cell lymphoma
--Extranodal NK/T, nasal type
--Subcutaneous panniculitis-like
--Primary cutaneous T-cell lymphoma
--Primary leukemic T-cell lymphoma
- Following B-cell lymphoma entities:
--Transformed indolent B-cell lymphomas
--Post-transplant B-cell lymphoproliferative disease
--HIV-associated B-cell lymphoma
- Concurrent severe and/or uncontrolled medical disease which is not lymphoma-related
- Left ventricular ejection fraction (LVEF) < 45%
- Suspected or documented central nervous system involvement by NHL
- Patients known to be antigen positive for HIV and/or hepatitis B and/or hepatitis C
- Patients with active, uncontrolled infections
- Vaccination with live, attenuated vaccines within 4 weeks of inclusion
- Pregnant and/or breastfeeding women
- History of active cancer during the past 5 years, except basal carcinoma of the skin or stage 0 cervical carcinoma
- Known hypersensitivity to one or more of the study drugs
- Unwillingness or inability to comply with the protocol
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-000758-39-NL |
| CCMO | NL60809.078.17 |