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A phase II study evaluating the effect of the addition of lenalidomide to R-CHOP for patients with newly diagnosed MYC positive DLBCL and BCL-U.

Phase 2
Completed
Conditions
Diffuse Large B Cell Lymophoma
10025320
Registration Number
NL-OMON47340
Lead Sponsor
HOVO
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
82
Inclusion Criteria

1. DLBCL or BCL-U, histologically confirmed according to the WHO classification 2008 with a MYC rearrangement as determined by FISH comprising:
- single hit (SH MYC+ lymphoma, not fulfilling the criteria for Burkitt Lymphoma ) or
- double hit lymphoma (DH) MYC+/BCL2+ or MYC+/BCL6+ or
- triple hit lymphoma (TH) MYC+/BCL2+/BCL6+
2. Age * 18 year
3. No prior treatment except
- local radiation or short course (max 7 days) steroids (max 100 mg/day)
- 1 course of R-CHOP in case MYC positivity became evident during first cycle of treatment
4. WHO performance status (PS) 0-3, status 4 only if disease related (see appendix C)
5. Ann Arbor stage II-IV
6. Measurable disease: on contract-enhanced CT scan at least 1 lesions/node with a long axis of >1.5 cm and at least one positive lesion on 18-F-FDG-PET scan.
7. Negative pregnancy test at study entry
8. Patient is willing and able to adhere to the requirements of the lenalidomide Pregnancy Prevention Risk Management Program
9. Written informed consent

Exclusion Criteria

1. All histopathological diagnoses other than DLBCL not otherwise specified or BCL-U according to the WHO classification 2008 (like Burkitt lymphoma, DLBCL associated with chronic inflammation), irrespective of the presence of MYC rearrangement
2. Known history of indolent lymphoma, or presence of indolent lymphoma in the diagnostic lymph node. If during screening localization of an indolent lymphoma in the bone marrow biopsy is diagnosed, the patient is eligible.
3. Absence of contrast-enhanced CT scan (neck, thorax, abdomen, pelvis) and 18F-FDG PET scan performed before first cycle of R-CHOP
4. Inadequate renal function or creatinine clearance < 30 mL/min (after rehydration)
5. Inadequate hepatic function: bilirubin > 3 times ULN (total) except patients with Gilbert's syndrome as defined by > 80% unconjugated bilirubin
6. Inadequate hematological function: ANC < 1.0x109/L or platelets < 75x109 /L unless lymphoma related
7. CNS localization of the lymphoma. Liquor analysis before start of treatment is only necessary in case of suspicion
8. Female subject pregnant or breast-feeding
9. History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma
10. Active symptomatic ischemic heart disease, myocardial infarction, or congestive heart failure within the past year. If echo or MUGA is obtained the LVEF should exceed 40%
11. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.) that would jeopardize the patient's ability to receive the regimen with reasonable safety
12. HIV positivity
13. Active Hepatitis B or C infection as defined by positive serology and transaminitis. Non-active Hepatitis B carriers may be included if protected with lamivudine
14. Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D)
15. Severe neurological or psychiatric disease
16. Current participation in another clinical trial interfering with this trial
17. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
18. Claustrofobia to the extent that PET-CT is impossible

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Complete remission rate as determinded by<br /><br>- End-of-treatment PET-CT scan<br /><br>- negative bone marrow examination in case of localizaton of DLBCL and BLC-U at<br /><br>diagnosis</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>- Event Free Survival (EFS) , defined as time from registration until no CR on<br /><br>protocol, relapse or death from any cause, whichever comes first<br /><br>- Overall survival (OS), calculated from registration until death from any<br /><br>cause Patients still alive or lost to follow up are censored at the last date<br /><br>known to be alive.<br /><br>- Disease free survival (DFS) from time of complete remission. DFS is defined<br /><br>as duration from start of CR to relapse or death from any cause, whichever<br /><br>comes first, and applies only to patients who achieved CR.<br /><br>- The relationship between mid-treatment 18F-FDG PET-CT result and<br /><br>end-of-treatment 18F-FDG PET-CT result.</p><br>
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