Main info

Identificatie:

HO119 MCL

Sponsor:

LYSARC

Working group party:

Lymphoma

Age:

>= 60

Stadium:

1st lijn

Echelon:

Level D

Included patients:

75

(of 100)

Active sites:

24

(of 25)

Title:

Efficacy of alternating immunochemotherapy consisting of RCHOP + R-HAD versus R-CHOP alone, followed by maintenance therapy consisting of additional lenalidomide with rituximab versus rituximab alone for older patients with mantle cell lymphoma

Timeline

News

Flow

Details

Phase:

Prospective randomized Phase III study

Monitoring Type:

Study Specific

Objectives:

The primary objective of the trial is to evaluate whether the addition of lenalidomide to rituximab maintenance improves progression free survival (PFS) compared to standard rituximab maintenance after response to induction chemotherapy in older patients with mantle cell lymphoma not suitable for autologous stem cell transplantation.
Secondary objectives are

• to compare efficacy and safety of the maintenance regimens in terms of secondary endpoints
• to evaluate whether the introduction of cytarabine into induction improves clinical outcome compared to standard R-CHOP in older patients with mantle cell lymphoma not suitable for autologous stem cell transplantation. This objective will be answered in a confirmatory way with overall survival as primary variable of interest.
• to compare efficacy and safety of the induction regimens in terms of other secondary endpoints

Eligibility

Inclusion Criteria:

Inclusion criteria for randomization 1
Patients must satisfy all the following criteria at study entry to be randomized in the trial:

• signed informed consent form
• Biopsy-proven mantle cell lymphoma according to WHO classification, including evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32)
• ≥ 60 years of age and ineligible for autologous transplant
• Ann Arbor stage II-IV
• previously untreated (except for patients randomized directly for maintenance treatment who will receive 8 RCHOP before registration in the trial)
• ECOG performance status ≤ 2
• Male subjects must:
  • agree to use a condom during sexual contact with a woman of childbearing potential, even if they have had a vasectomy, throughout lenalidomide therapy
  • agree to not donate semen during lenalidomide therapy.
• All subjects must:
  • have an understanding that the lenalidomide could have a potential teratogenic risk.
  • agree to abstain from donating blood while taking lenalidomide therapy
  • agree not to share study medication with another person.
  • be counselled about pregnancy precautions and risks of foetal exposure.

Additional Inclusion criteria for randomization 2
To be randomized for maintenance, the patient must satisfy all inclusion criteria for randomization 1 and the following criteria:

• CR, CRu or PR after induction treatment, determined as per Cheson 1999 criteria (see Appendix G), by investigator even for patients enrolled during the run-in phase.
• During the run-in period of 6 months starting from the date of the first randomization in the trial up to May 2014: in case of direct randomization into maintenance phase, patient must have been treated in first line by 6-8 cycles of R-CHOP.

Exclusion Criteria:

Exclusion criteria for randomization 1
The presence of any of the following will exclude a subject from enrollment:

• Female of childbearing potential (i.e. without natural menopause for at least 24 consecutive months, a hysterectomy or bilateral oophorectomy)
• Any of the following laboratory abnormalities at diagnosis, if not related to lymphoma:
  • Absolute neutrophils count <1,000 /mm^3 (1.0 x 10^9/L) if not result of a bone marrow infiltration.
  • Platelet count < 75,000/mm^3 (75 x 10^9/L) if not result of a bone marrow infiltration.
  • Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) >3.0 x upper limit of normal (ULN).
  • Serum total bilirubin > 1.5 ULN (except if due to Gilbert’s syndrome)
• Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) < 30 mL / min.
• Central Nervous System involvement by lymphoma
• Contraindication for medical DVT prophylaxis for patients at high risk for DVT
• Prior history of malignancies other than MCL unless the subject has been free of the disease for ≥ 5 years. Exceptions include the following:
  • Basal cell carcinoma of the skin,- Squamous cell carcinoma of the skin,
  • Carcinoma in situ of the cervix,
  • Carcinoma in situ of the breast,
  • Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b).
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient to receive the study medication as planned.
• Poor cardiac function (LVEF < 50%) on echocardiography
• Seropositivity for human immunodeficiency virus (HIV, mandatory test) at study entry

Seropositivity for hepatitis C virus (HCV, mandatory test) at study entry,
Active viral infection with hepatitis B virus (HBV, mandatory test) at study entry:

• HBsAg positive
• HBsAg negative, anti-HBs positive and anti-HBc positive Patients with prior Hepatitis B must be given antiviral prophylaxis and HBV DNA monitored.

Note: Patients who are HBsAg negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative are eligible.
HIV, HVC and HBV tests are mandatory

• Uncontrolled illness including, but not limited to:
  • Active infection requiring parenteral antibiotics.
  • Uncontrolled diabetes mellitus
  • Chronic symptomatic congestive heart failure (Class NYHA III or IV).
  • Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
  • Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia.
• Prior ≥ Grade 3 allergic hypersensitivity to thalidomide.
• Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide.
• Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies.
• Subjects with ≥ Grade 2 neuropathy.
• Prior use of lenalidomide
• Participation in another clinical trial within three weeks before randomization in this study

Additional exclusion criteria for randomization 2
To be randomized for maintenance, the patient must satisfy all exclusion criteria for
randomization 1 and the following criteria:

• The presence of any exclusion criteria of randomization 1 or of the following criteria will exclude a subject from enrollment in the maintenance phase:
• SD or PD after induction treatment determined as per Cheson 1999 criteria (see Appendix G) by investigator.
• Patient treated by induction immuno-chemotherapy other than 6-8 cycle of R-CHOP21 or 2-3 cycles of R-CHOP21 / 2-3 cycles of R-HAD28 (alternating)
• Patients with serious underlying medical conditions, which could impair the ability to receive maintenance treatment
• Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of < 30 mL / min at screening for maintenance.
• ANC is < 1,000 cells/mm³ (1.0 X 10^9/L) at screening for maintenance;
• Platelet count is < 50,000 cells/mm³ (50 X 10^9/L) at screening for maintenance.

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals