Primary objectivesPart A of the study (if applicable):1. To assess the safety and tolerability of Lenalidomide added to standard induction chemotherapy for AML and select the feasible dose level for part B of the study2. To assess in a randomized…
ID
Source
Brief title
Condition
- Leukaemias
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part A:
DLT of Lenalidomide at three dose levels (10mg, 15mg and 20mg) added to
standard chemotherapy
DLT is defined as: Death within 31 days of start cycle I
Part B:
To assess in a randomized comparison the effect of the in Part A selected dose
of Lenalidomide on the CR rate.
Secondary outcome
Part B
- Overall survival (time from registration till the death of the patient.)
- Event free survival (i.e., time from registration to induction failure (i.e.
no CR on induction), death or relapse whichever occurs first)
- Disease free survival (time from CR on protocol treatment until relapse or
death, whichever comes first)
- Prognostic value of molecular markers and gene expression profiles of the
leukemia assessed at diagnosis
- Prognostic value of minimal residual disease (MRD) measurements following
therapy by standardized sampling of marrow/blood
Background summary
HOVON/SAKK Cooperative groups concentrate their developmental therapeutic
efforts for the 66+ yrs age segment of AML patients and very poor risk AML of
any age, on developing effective treatments for these patients, for whom
current treatment in spite of active clinical research has remained highly
unsatisfactory. Therefore new treatment modalities are introduced and evaluated
in combination with standard chemotherapy. For this an approach is chosen with
multiple parallel randomized phase II studies that will be conducted within the
frame of a master protocol.
This will allow for introducing and evaluating new treatment modalities in
combination with standard chemotherapy.
In this randomized Phase II study Lenalidomide is added to the standard
chemotherapy for remission induction therapy of adults of age 66 years or older
with acute myeloid leukaemia(AML), refractory anemia with excess of
blasts(RAEB) with International Prognostic Score System (IPSS)>+ 1.5 or
patients< 66 year with very poor risk AML. The aim of this study is to examine
whether the addition of Lenalidomide to standard chemotherapy is feasible and
whether the percentage of patients achieving a Complete Remission is promising
enough as compared to the control arm to start a Phase III study. Lenalidomide
is given orally in addition to daunorubicin and cytosin-arabinoside in cycle I
and to cytosin-arabinoside in Cycle II during day 1-21. In the first part A of
the study the feasibility of three dose levels (10,15,20mg) will be compared to
the treatment without Lenalidomide in a randomized design. In the second part
of the study the assigned dose will be tested compared to the control arm with
CR as primary endpoint.
Study objective
Primary objectives
Part A of the study (if applicable):
1. To assess the safety and tolerability of Lenalidomide added to standard
induction chemotherapy for AML and select the feasible dose level for part B of
the study
2. To assess in a randomized comparison the effect of Lenalidomide on the CR
rate.
Part B of the study:
1. To assess the safety and tolerability of Lenalidomide added to standard
induction chemotherapy for AML as regards the selected dose level of
Lenalidomide
2. To assess in a randomized comparison the effect of the in Part A selected
dose of Lenalidomide on the CR rate.
Secondary objectives
For part B:
1. To determine the efficacy profile (event free survival and disease free
survival and overall survival) associated with the two therapy regimens.
2. To measure MRD by immunophenotyping in relation to clinical response
parameters.
3. To identify potential biomarkers predictive of response, event free survival
and disease free survival.by exploratory genomic analysis (microarray, gene
mutations)
Study design
This is a prospective, open label, multicenter study that is conducted in the
frame of a masterprotocol with multiple parallel randomized phase II studies.
The scheme of this design consists of one arm with the standard treatment for
AML as compared to various arms with experimental treatments. Patients in this
study are treated with standard induction chemotherapy with or without
lenalidomide. During the first part A of the studies the feasibility of
combining lenalidomide with DNR/Ara-C will be evaluated and the dose of
lenalidomide will be selected. Decisions regarding dose escalation,
continuation with starting dose level or stopping, are based on the incidence
of DLT (dose limiting toxicity: death within 31 days of start cycle I and
before start cycle II .) During part B of the study that will be conducted with
the selected dose of the added new drug, the CR rate (primary endpoint) and
secondary endpoints (EFS, DFS, OS, as well as MRD and genomic profiling) will
be assessed.
Intervention
In the experimental arm Lenalidomide will be added to the standard daunorubicin
-cytarabin-arabinoside in cycle I and to cytarabine-arabinoside in cycle II
The study starts at dose level 10mg orally day 1-21 in both cycles and if
possible escalated to 20mg. At each dose level the decision to stop or escalate
will be made on the basis of the incidence of DLT defined as Death within 31
days of start cycle I and before start cycle II.
Study burden and risks
The addition of Lenalidomide can increase the possibilities of toxicities.
Lenalidomide has been given as monotherapy and also in combination with
chemotherapy but not with this peticular antileukemic standard chemotherapy
regimen. So unexpected toxicities are possible.
Lenalidomide is associated with myelosuppression and other toxicities like
nausea, vomiting, diarrhea thrombosis and infections. At time of the normal
bone marrow punctions a limited amount of extra bone
marrow will be collected via the same needle. This is abouth 30 ml at start and
10 ml at follow up .
De Boelelaan 1117
Amsterdam 1007 MB
NL
De Boelelaan 1117
Amsterdam 1007 MB
NL
Listed location countries
Age
Inclusion criteria
· Patients eligible for standard chemotherapy.
· Patients >= 66 years with a cytopathologically confirmed diagnosis according WHO
classification of
o AML (not APL) or
o refractory anemia with excess of blasts (RAEB) with
an IPSS score >= 1.5
OR
Patients of any age >= 18 years with a cytopathologically confirmed diagnosis
according WHO classification of
o AML with very poor risk AML
· Subjects with secondary AML progressing from antecedent (at least 4 months
duration) myelodysplasia are also eligible.
· SGOT (AST) and SGPT (ALT) <= 1.5 x the upper limit of the normal range (ULN) at
the laboratory where the analyses were performed.
· Total serum bilirubin level <= 1.5 x the ULN at the laboratory where the analysis
was performed.
· Serum creatinine concentration <= 1.5 x the ULN at the laboratory where the
analysis was performed.
· WHO performance status <= 2
· Written informed consent.
· Female patients of childbearing potential must have a negative serum pregnancy
test within 2 weeks prior to enrollment.
· Male and female patients must use an effective contraceptive method during the
study and for a minimum of 6 months after study treatment.(see protocol
appendix J for more information and specific requirements)
Exclusion criteria
· Acute promyelocytic leukemia
· Patients previously treated for AML (any antileukemic therapy including
investigational agents), a short treatment period (< 2 weeks) with Hydroxyurea is
allowed
· Past or current history (within the last 2 years prior to randomization) of
malignancies except for the indication under this study and curatively treated:
* Basal and squamous cell carcinoma of the skin
* in situ carcinoma of the cervix
· Blast crisis of chronic myeloid leukemia
· Clinically significant (i.e. active) cardiovascular disease, for example
cerebrovascular accidents (<= 6 months prior to randomization), myocardial
infarction (<= 6 months prior to randomization), unstable angina, New York Heart
Association (NYHA) grade II or greater congestive heart failure
· Patients with a history of non-compliance to medical regimens or who are
considered unreliable with respect to compliance
· Patients with any serious concomitant medical condition which could, in the
opinion of the investigator, compromise participation in the study.
· Patients who have senile dementia, mental impairment or any other psychiatric
disorder that prohibits the patient from understanding and giving informed
consent.
· Pregnant or lactating patients.
· Current concomitant chemotherapy, radiation therapy, or immunotherapy other
than as specified in 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 | EUCTR2009-013094-17-NL |
| CCMO | NL29253.078.09 |