Main info

Identificatie:

HO130 NHL

Sponsor:

HOVON

Working group party:

Lymphoma

Age:

>= 18

Stadium:

1st lijn

Echelon:

Level D

Included patients:

85

(of 85)

Active sites:

23

(of 23)

Title:

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.

Timeline

News

Flow

Details

Phase:

Prospective Phase II study

Monitoring Type:

Not any more

Objectives:

Primary objective
To evaluate the efficacy of the combination of lenalidomide and R-CHOP in MYC+ DLBCL patients in terms of CR rate by end-of-treatment F-FDG PET-CT scan and BM.

For DH -DLBCL patients the complete remission rate on R-CHOP was reported by Green at 64%in 2012. Later publications showed CR rates of 35%, 40% and 50%. For all DLBCL patients the CR/Cru rate after R-CHOP will be 58-63%. In this protocol we aim to improve the CR rate by end-of-treatment as assessed by F-FDG PET-CT from 45% to 60%.

Secondary objectives
To evaluate the efficacy of the addition of lenalidomide to R-CHOP for MYC+ DLBCL patients in terms of EFS, DFS and OS.

To evaluate the value of mid-treatment F-FDG PET-CT scanning in predicting end-of-treatment F-FDG PET-CT result.

Eligibility

Inclusion Criteria:

• 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+
• Age ≥ 18 year
• 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
• WHO performance status (PS) 0-3, status 4 only if disease related (see appendix C)
• Ann Arbor stage II-IV
• Measurable disease: on contrast-enhanced CT scan at least 1 lesions/node with a long axis of >1.5 cm and at least one positive lesion on 18F-FDG PET scan.
• Negative pregnancy test at study entry
• Patient is willing and able to adhere to the requirements of the lenalidomide Pregnancy Prevention Risk Management Program
• Written informed consent
• Patient is capable of giving informed consent.

Exclusion Criteria:

• 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
• 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.
• Absence of contrast-enhanced CT scan (neck, thorax, abdomen, pelvis) and 18F-FDG PET scan performed before first cycle of R-CHOP
• Inadequate renal function or creatinine clearance < 30 mL/min (after rehydration). Creatinine clearance may be calculated by Cockcroft –Gault formula: CrCl = (140 - age [in years]) x weight [kg] (x 0.85 for females)/ (0.815 x serum creatinine [μmol/L])
• Inadequate hepatic function: bilirubin > 3 times ULN (total) except patients with Gilbert's syndrome as defined by > 80% unconjugated bilirubin
• Inadequate hematological function: ANC < 1.0x10^9/L or platelets < 75x10^9 /L unless lymphoma related
• CNS localization of the lymphoma. Liquor analysis before start of treatment is only necessary in case of suspicion
• Female subject pregnant or breast-feeding
• History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma
• 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%
• 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
• HIV positivity
• 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 (see 9.4)
• Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D)
• Severe neurological or psychiatric disease
• Current participation in another clinical trial interfering with this trial
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Claustrophobia to the extent that PET-CT is impossible.

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals