| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Waldenstrom’s Macroglobulinemia (MW) |
| Macroglobulinémie de Waldenstrom (MW) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patient with relapsed/refractory Waldenstrom’s Macroglobulinemia |
| Patient en rechute ou réfractaire d'une macroglobulinémie de Waldenstrom |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate in advanced WM whether the progression free survival (PFS) is improved by obinutuzumab + idelalisib. |
| Evaluer dans la macroglobulinémie de Waldenstrom avancée si la survie sans progression est améliorée par obinutuzumab + Idelalisib |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate ORR (overall response rate) including CR (complete response), VGPR (very good partial response), PR (partial response) and MR (minor response)
- To evaluate the duration of response (RD), time to treatment failure (TTF), time to next treatment (TNT), cause-specific survival and overall survival (OS) for all study patients
- To evaluate the time to best response (TBR)
- To evaluate best overall response (BOR)
- To evaluate the safety of the combination of idelalisib + obinutuzumab
- To evaluate the efficacy according to MYD88 and CXCR4 mutations
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Patient information and written informed consent
- Age 18 years or older
- Confirmed CD20 positive WM, according to the recommendations of the 2nd Workshop on WM.
- Presence of at least one criterion for initiation of therapy, according to the 2nd Workshop on WM.
Recurrent fever, night sweats, weight loss, fatigue
Hyperviscosity
Lympadenopathy which is either symptomatic or bulky (≥5cm in maximum diameter)
Symptomatic hepatomegaly and/or splenomegaly
Symptomatic organomegaly and/or organ or tissue infiltration
Peripheral neuropathy due to WM
Symptomatic cryoglobulinemia
Cold agglutinin anemia
Immune hemolytic anemia and/or thrombocytopenia
Nephropathy related to WM
Amyloidosis related to WM
Hemoglobin ≤10g/dL
Platelet count <100x109/L
- Prior treatment for WM comprising at least one regimen containing a therapeutic anti-CD20 monoclonal antibody (rituximab) administered for ≥ 2 doses of antibody treatment and /or a therapeutic chemotherapy (eg, alkylating agent, purine analogue, bendamustine) administered for ≥ 2 cycles of treatment
- Patients may be either relapsing (progressing at least 6 months after the last administration of first line or subsequent treatment) or refractory (progressing on or within 6 months of first line or subsequent treatment)
- Number of prior regimens/lines : 1 to 3
- Life expectancy >3 months.
- ECOG ≤ 2.
- Meet the following pre-treatment laboratory criteria at the screening visit conducted within 28 days of study enrolment:
ASAT (SGOT): 2.5 times the upper limit of institutional laboratory normal value.
ALAT (SGPT): 2.5 times the upper limit of institutional laboratory normal value.
Total bilirubin: 1.5x times the upper limit of institutional laboratory normal valueunless clearly related to the disease or Gilbert’s syndrome
Calculated or measured creatinine clearance by MDRD: 40 mL/minute.
- Premenopausal fertile females must agree to use a highly effective method of birth control for the duration of the therapy up to 18 months after end of therapy. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.
- Men must agree not to father a child for the duration of therapy and 6 months afterand must agree to advice a female partner to use a highly effective method of birth control.
|
|
| E.4 | Principal exclusion criteria |
- Prior treatment with phosphatidylinositol 3 kinase (PI3K) inhibitors including idelalisib or GA101;
- History of anaphylactic reaction following exposure to humanized monoclonal antibodies.
- Previous allogeneic transplantation
- Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study
- History of other malignancy or chemotherapy/radiotherapy for any neoplastic disease other than WM prior to the study.EXCEPTION : History of malignancy except basal cell carcinoma of the skin, in situ carcinoma of breast or cervix treated surgically with curative intent, or any malignancy that has been in CR for 5 years at minimum, or as deemed appropriate for inclusion in the trial as per approval by the investigator
- Medical condition requiring the long-term (estimated to be more than one month) use of oral corticosteroids.
- Patients with signs of bacterial, viral or fungal infection
- CMV PCR or antigenemia testing positive
- Known history of drug induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension
- HIV antibody positive
- Positive HBV HBsAG (surface) or positive HBC (core) antibody
Note: The both should be tested and both have to be negative to be eligible for inclusion
- Known history of drug induced pneumonitis
- On-going inflammatory bowel disease
- Lactation/pregnancy
- Concurrent severe diseases which exclude the administration of therapy:
*Heart insufficiency NYHA grade III/IV, LVEF < 50% and or RF <30%, myocardial infarction within the past 6 months prior to study
*Severe chronic obstructive lung disease with hypoxemia
*Severe diabetes mellitus
*Hypertension difficult to control
*Cerebral dysfunction
- Richter’s syndrome
- Cardiac amyloidosis
- Any of the following laboratory abnormalities, if not related to lymphoma:
*Absolute neutrophils count <1.5 x 109/L if not result of a bone marrow infiltration
*Platelet count <75 x 109/L if not result of a bone marrow infiltration.
*Central Nervous System involvement by lymphoma
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation
- Patient with mental deficiency preventing proper understanding of the requirements of treatment
- Person major under law control.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The aim of this study is to compare the total progression free survival (PFS) of relapsed/refractory WM patients with ECOG between 0 and 2, after chemo-free treatment combination with obinutuzumab + idelalisib as compared to that of the usual therapy based on chemo free treatments with Rituximab |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| PFS will be calculated from the date of inclusion to the following events (progression date and the date of the death if it occurred earlier). In the absence of progression and death, PFS duration will be censored at the stopping date or the date of last follow-up |
|
| E.5.2 | Secondary end point(s) |
- To evaluate ORR (overall response rate): CR (complete response)+ VGPR (very good partial response) + PR (partial response) +MR (minor response)
- To evaluate the duration of response (RD), time to treatment failure (TTF), time to next treatment (TNT), cause-specific survival and overall survival (OS) for all study patients
- To evaluate the time to best response
- To evaluate best overall response
- To evaluate the safety of the combination of idelalisib + obinutuzumab
- To evaluate the efficacy according to MYD88 and CXCR4 mutations. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- First evaluation: four weeks after end of last cycle of Obinutuzumab
- After 730 days of Idelalisib
- At the end of the study
- Toxicity evaluation during all the study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| 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 | No |
| 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 | 28 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| The end of the trial takes place the last visit of the last patient included |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
Print
