| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Follicular Lymphoma (FL);
Lymphoplasmacytic (lymphoplasmacytoid) Lymphoma (LPL) / Waldenstrom’s
macroglobulinemia (WM) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10016905 |
| E.1.2 | Term | Follicle centre lymphoma, follicular grade I, II, III recurrent |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025334 |
| E.1.2 | Term | Lymphoplasmacytic type lymphoma (Kiel Classification) refractory |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary:
1. To determine the MTD of SPC2996 in combination with rituximab in
patients with relapsed follicular or lymphoplasmacytic non-Hodgkin’s
lymphoma
2. To determine the overall response rate (Complete Response [CR] +
Partial Response [PR]) of the combination of SPC2996 and rituximab
in the treatment of relapsed follicular or lymphoplasmacytic non-
Hodgkin’s lymphoma
3. To determine the safety and tolerability of the combination of
SPC2996 and rituximab in patients with relapsed follicular or
lymphoplasmacytic non-Hodgkin’s lymphoma |
|
| E.2.2 | Secondary objectives of the trial |
Secondary:
To determine:
1. median duration of response of the combination of
SPC2996 and rituximab to
2. median progression-free survival of patients treated
with SPC2996 and rituximab
3. median time to subsequent therapy for patients
treated with SPC2996 and rituximab
4. To investigate the pharmacokinetics (PK) of SPC2996 given as
weekly doses for 10 weeks over two 5-week treatment periods
Exploratory (Part 2 only)
Pre- and Post-therapy assessment of:
1. bcl-2 protein expression in lymph node tissue (immunohistochemical analysis)
2. correlates of response (high-density genomic profiling technology)
3. pharmacological effect on a molecular basis by analyzing changes in the gene expression profile in lymph node tissue
4. presence of bcl-2 (t14;18) translocation in lymph node biopsies and paraffin-embedded tissue (by FISH)
5. To examine the correlation of serum beta 2-microglobulin levels with
response |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Disease specific genetic and exploratory Analysis:
Under a separate informed consent patients will be offered to provide tissues for banking (lymph nodes, plasma and whole blood). Patients will be informed that the tissue will be used for disease specific genetic and non-genetic analyses for correlation between response and treatment. |
|
| E.3 | Principal inclusion criteria |
Key inclusion criteria:
1. Age 18 years or older at the time of informed consent
2. Histologically confirmed relapsed follicular grade 1-3a or
lymphoplasmacytic non-Hodgkin’s lymphoma
3. Progressive disease following at least one prior standard therapy for
non-Hodgkin’s lymphoma
4. Two or fewer prior regimens containing rituximab (maintenance
rituximab following initial or subsequent therapy is not considered a
separate regimen), with a time to progression (TTP) of at least
6 months following the most recent dose of rituximab
5. Measurable disease with at least one lesion suitable for reproducible
measurements over 2 cm in maximum diameter
6. ECOG performance status 0-2
7. Absolute neutrophil count (ANC) ≥ 1,500/mm3 (or ≥ 1,000/mm3 if
due to extensive bone marrow involvement with NHL or
splenomegaly)
8. Absolute lymphocyte count (ALC) ≤ 5,000/mm3
9. Platelet count ≥ 75,000/mm3
10. Haemoglobin ≥ 10 g/dL
11. Bilirubin ≤ 2 mg/dL
12. AST and ALT ≤ 2.5 x ULN (upper limit of normal)
13. Alkaline phosphatase ≤ 3 x ULN (or 5 x ULN if due to involvement
with NHL)
14. Creatinine ≤ 1.5 x ULN
15. Willing to practice effective contraception during and for 3 months
after the study treatment (applies to males only; females must be of
non-child-bearing potential).
16. Willing to abstain from the use of alcohol for the duration of study
treatment |
|
| E.4 | Principal exclusion criteria |
Key exclusion criteria:
1. Pregnant or nursing
2. Females of child-bearing potential, defined as age ≤ 50 with premenopausal
levels of follicle stimulating hormone (FSH) and/or
oestradiol and who are not surgically sterile. Womaen who are not
surgically sterile and are less than 60 years of age will have a serum
FSH, oestradiol level and pregnancy test performed during screening
to confirm lack of childbearing potential.
3. Rituximab refractory, as defined by time to progression of less than
6 months following the most recent rituximab-containing regimen,
progression of disease while on rituximab maintenance, or by lack of
response to the most recent rituximab-containing regimen
4. Autologous bone marrow or stem cell transplant within 6 months
before study entry
5. Prior allogeneic transplant
6. Patients who are red blood cell or platelet transfusion dependent
7. Cancer radiotherapy, biologic therapy, chemotherapy or
investigational agents within 4 weeks before study entry (6 weeks if
nitrosourea or mitomycin-C)
8. Prior antibody therapy for lymphoma (including radioimmunotherapy)
within 6 months of study entry
9. Known HIV infection
10. Active infection, including opportunistic infection, hepatitis B or hepatitis C
11. Presence of significant hepatic diseases. e.g. hepatic cirrhosis or
alcoholic liver disease
12. Diagnosis of chronic lymphocytic leukaemia, small lymphocytic
lymphoma, or aggressive non-Hodgkin’s lymphoma
13. Active malignancy or prior malignancy within 3 years of study entry.
Cervical carcinoma-in-situ, non-melanoma skin cancer and superficial
bladder cancer are allowed if adequately treated
14. NYHA class III or IV congestive heart failure
15. Uncontrolled angina pectoris
16. Myocardial infarction within the past 6 months
17. Severe uncontrolled ventricular arrhythmias
18. Less than 4 weeks following major surgery
19. Known hypersensitivity to murine proteins or any component of
rituximab
20. Concurrent therapy with investigational agents or on a clinical trial
with active therapy (non-treatment studies are allowed)
21. Patients on therapeutic anticoagulation treatment (e.g. warfarin or full
dose low molecular weight heparin) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Response will be assessed at Week 14 and every 3 months afterward until
disease progression or for 18 months, whichever occurs first. Response in
this study will be evaluated according to International Working Group
response criteria, as recently revised (Ref: J Clin Oncol 25(5):579-586,
2007) and graded as complete response (CR), partial response (PR), stable
disease (SD) and progressive disease (PD) using CT scans and physical
examination. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Dose finding, Safety & efficacy |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 21 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
After the end of study therapy (Week 13), all patients will be followed up for a period of 18 months or until disease progression, whichever occurs
first. At 3-month intervals (or until disease progression occurs), patients will return to the study site for disease assessment as described in section 6.1.5.2 of the protocol. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
Print
