Primary objective:Assesment of feasibility and toxicity of T cell depleted NMA Allo-SCT followed by lenalidomide or lenalidomide combined with bortezomib,and subsequent DLI; as treatment of relapsed multiple myeloma.Secondary objectives:To…
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Failure free duration (FFD) at 9 months post-transplant. Patients count as a
failure (= event) at the earliest time point within 9 months after Allo-SCT at
which any of the following events occurs:
- Onset of acute GvHD grade 3-4 without prior DLI;
- Onset of extensive chronic GvHD without prior DLI;
- Non-hematological toxicity CTCAE grade 4;
- Systemic therapy for uncontrolled myeloma other than the assigned study
treatment of lenalidomide or lenalidomide/bortezomib and DLI
- Death not due to (progression of) MM, which is in fact TRM.
Patients without a failure within 9 months post Allo-SCT will be censored at 9
months, at the date of progression, or when they go off protocol treatment,
whichever comes first.
Secondary outcome
- Toxicity profile and compliance related to each treatment step and intervals
between treatment steps (Allo-SCT, consolidation chemotherapy as well as
pre-emptive DLI);
- Percentage of patients with a 1st pre-emptive DLI within 6-9 months from the
date of Allo-SCT;
- Response, improvement of response and conversion to full donor chimerism
during the separate treatment phases (i.e. from Allo-SCT until consolidation;
from consolidation to DLI; and after DLI);
- CR rate
- Progression-free survival (PFS; i.e. time from registration until
progression, relapse or death, whichever comes first);
- PFS from Allo-SCT;
- Overall survival (OS) measured from time of registration;
- OS from Allo-SCT;
- The poportion of patients that complete 1, 2 resp. 3 induction cycles;
- Quality of life as defined by the EORTC QLQ-C30 and QLQ-MY20.
Background summary
This study will explore the feasibility and efficacy of T-cell depleted NMA
Allo-SCT, followed by early consolidation with lenalidomide with or without
bortezomib and subsequent DLI in relapsed myeloma patients. Patients with
relapsed or progressive disease after first line therapy have a poor prognosis.
This is illustrated by the median survival of only 19 months after relapse from
thalidomide maintenance of patients who were included in the HOVON 50 study. T
cell depleted NMA Allo-SCT will avoid the occurrence of acute and chronic GvHD
and will make it possible to create a platform for subsequent immune therapy
like pre-emptive donor lymphocyte infusion. Timely consolidation after T cell
depletion however is necessary to avoid early relapse. As consolidation
strategy we will use either the thalidomide analog lenalidomide (CC-5013) or
lenalidomide combined with bortezomib. Lenalidomide as this drug has a low
toxicity profile, is highly effective against myeloma and has strong immune
modulating effects. Bortezomib once weekly, may increase the efficacy of
lenalidomide while on the other hand it may temper undesirable excessive immune
stimulatory effects of lenalidomide and helps to separate the GvM effect from
GvHD.
Study objective
Primary objective:
Assesment of feasibility and toxicity of T cell depleted NMA Allo-SCT followed
by lenalidomide or lenalidomide combined with bortezomib,and subsequent DLI; as
treatment of relapsed multiple myeloma.
Secondary objectives:
To investigate the efficacy of this regimen in terms of complete remission
rate, overall and progression free survival.
To evaluate the quality of life with these regimens.
Study design
Randomized phase II
Intervention
T cell depleted NMA Allo-SCT followed by 3 cycles of lenalidomide 10 mg/daily
or lenalidomide 10 mg/daily combined with weekly bortezomib 1.3 mg/m2 and
preemptive DLI. The conditioning of NMA Allo-SCT is performed with
melphalan/fludarabine and in vitro and in
vivo T cell depletion with Alemtuzumab (for MUD in combination with
ciclosporin).
Study burden and risks
Patients with relapsed multiple myeloma have a limited life expectancy. A
potential benefit for these patients is Allo-SCT to induce prolonged remissions
especially when this procedure is followed by early consolidation with novel
antimyeloma agents and subsequent pre-emptive DLI that may enhance the Graft
versus Myeloma effect. The risks associated with this procedure is an estimated
Treatment Related Mortality between 10-15 % that is associated with Allo-SCT
and reduced quality of life due to acute and chronic GvHD.
VUMC, 4 noord 138 (PK 5 X 176), De Boelelaan 1117
NL - 1007 MB AMSTERDAM
NL
VUMC, 4 noord 138 (PK 5 X 176), De Boelelaan 1117
NL - 1007 MB AMSTERDAM
NL
Listed location countries
Age
Inclusion criteria
- Patients with multiple myeloma with a first relapse or progression after first line therapy;
- Relapsed or progressive patients have received reinduction therapy before entering this trial;
- At least PR after reinduction treatment;
- 18-65 years,inclusive
- HLA-identical sibling or unrelated donor completely matched (10/10) (excluding identical
twins);
- WHO-performance status 0-2;
- Written informed consent
Exclusion criteria
- No previous Allo-SCT;
- Severe pulmonary dysfunction (CTCAE grade III-IV, see protocol appendix D );
- Severe neurological or psychiatric disease;
- Patients with neuropathy, CTC grade 3 or higher;
- Significant hepatic dysfunction (serum bilirubin or transaminases * 3 times upper limit of
normal);
- Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration);
- Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes,
infection, hypertension, cancer, etc.);
- History of active malignancy during the past 5 years with the exception of basal carcinoma of
the skin or or carcinoma *in situ* of the cervix or breast;
- Patient known to be HIV-positive;
- Patients with brain disease with the exception of those patients whose brain disease has
been treated with either radiotherapy or surgery and remains asymptomatic, with no active
brain disease, as shown by CT scan or MRI, for at least 6 months;
- The development of erythema nodosum if characterized by a desquamating rash while taking
thalidomide, lenalidomide or borium;
- Pregnant or breast-feeding female patients. Negative pregnancy test at study is mandatory
for female patients of childbearing potential;
- Not able and not willing to use adequate contraception during therapy;
- Any psychological, familial, sociological and geographical condition potentially hampering
compliance with the study protocol and follow-up schedule;
- Severe cardiac dysfunction (NYHA classification II-IV, see protocol appendix E).
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 | EUCTR2010-018494-37-NL |
| CCMO | NL32525.000.10 |