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R-CHOP + R-HAD vs R-CHOP Followed by Maintenance Lenalidomide + Rituximab vs Rituximab for Older Patients With MCL

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ClinicalTrials.gov Identifier: NCT01865110
Recruitment Status : Recruiting
First Posted : May 30, 2013
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation

Tracking Information
First Submitted Date  ICMJE May 24, 2013
First Posted Date  ICMJE May 30, 2013
Last Update Posted Date March 13, 2019
Study Start Date  ICMJE November 2013
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2013)
Progression free survival [ Time Frame: 2.5 years ]
2.5 years after last patient randomized in maintenance
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01865110 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE R-CHOP + R-HAD vs R-CHOP Followed by Maintenance Lenalidomide + Rituximab vs Rituximab for Older Patients With MCL
Official Title  ICMJE Efficacy of Alternating Immunochemotherapy Consisting of R-CHOP + R-HAD vs R-CHOP Alone, Followed by Maintenance Therapy Consisting of Additional Lenalidomide + Rituximab vs Rituximab Alone for Older Patients With Mantle Cell Lymphoma
Brief Summary

This study aims to evaluate whether the addition of lenalidomide to rituximab-maintenance improves progression free survival (PFS) compared to standard rituximab maintenance after induction treatment consisting of R-CHOP + R-HAD vs R-CHOP alone in older patients (≥ 60 year old) with mantle cell lymphoma.

The treatments consist of two phases: induction treatment (3 R-CHOP21 + 3 cycles of R-HAD28 alternating) vs 8 cycles of R-CHOP21) followed by maintenance treatment (13 cycles of rituximab + 26 cycles of lenalidomide vs 13 cycles of rituximab).

Detailed Description

This study aims to evaluate whether the addition of lenalidomide to rituximab-maintenance improves progression free survival (PFS) compared to standard rituximab maintenance after induction treatment consisting of R-CHOP + R-HAD versus R-CHOP alone in older patients (≥ 60 year old) with mantle cell lymphoma. 643 patients will be randomized in induction phase and 433 in maintenance phase.

The treatments consist of two phases:

  • induction treatment will be 3 cycles of R-CHOP21 + 3 cycles of R-HAD28(alternating) versus 8 cycles of R-CHOP21 alone
  • maintenance treatment will be 13 cycles of rituximab every 8 weeks + 26 cycles of lenalidomide every 4 weeks vs 13 cycles of rituximab every 8 weeks.

Patients will be followed 2.5 years after the last patient randomized for maintenance for final analysis. All subjects who complete or discontinue the maintenance treatment for any reason will be followed for at least 3 years after his/her last study treatment administration in maintenance period for Second Primary Malignancies (SPM). A long term follow-up for progression/death will be done up to the end of period of SPM data collection.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mantle Cell Lymphoma
Intervention  ICMJE
  • Drug: R-CHOP
    R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) administered in 3 week cycles for 8 cycles
    Other Name: rituximab, CHOP
  • Drug: R-CHOP / R-HAD
    R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) administered in 3 week cycles for 3 cycles R-HAD (rituximab, cytarabine, dexamethasone) administered in 3 week cycles for 4 cycles alternating
    Other Names:
    • rituximab, CHOP
    • rituximab HD AraC
  • Drug: Rituximab
    Rituximab SC 1400 mg every 8 weeks for 24 months
    Other Name: Mabthera
  • Drug: Lenalidomide
    Lenalidomide 15 mg 3 weeks every 4 weeks for 24 months
    Other Name: Revlimid
Study Arms  ICMJE
  • Experimental: Induction experimental arm
    R-CHOP / R-HAD : Alternating 3 cycles of R-CHOP administered in 3 week cycles + 3 cycles of R-HAD administered in 4 week cycles.
    Intervention: Drug: R-CHOP / R-HAD
  • Active Comparator: Standart induction arm
    8 cycles of R-CHOP administered in 3 week cycles
    Intervention: Drug: R-CHOP
  • Experimental: Maintenance experimental arm
    lenalidomide + rituximab : 13 cycles of rituximab SC 1400 mg administered in 8 week cycles + 26 cycles Lenalidomide 15 mg 3 weeks every 4 weeks for 24 months
    Interventions:
    • Drug: Rituximab
    • Drug: Lenalidomide
  • Active Comparator: Maintenance standart arm
    13 cycles of rituximab SC 1400 mg administered in 8 week cycles for 24 months
    Intervention: Drug: Rituximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 29, 2013)
633
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2024
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Signed informed consent form Biopsy-proven MCL according to WHO classification

≥ 60 years of age and ineligible for autologous transplant Ann Arbor stage II-IV Previously untreated ECOG PS ≤ 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 criteria for randomization in maintenance phase:

  • CR, CRu or PR after induction treatment, determined as per Cheson 1999 criteria
  • During the run-in period of 6 months starting from the date of the first randomization in the trial: 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:

Female of childbearing potential

Any of the following laboratory abnormalities at diagnosis, if not related to lymphoma:

Absolute neutrophils count <1,000 /mm3 Platelet count < 75,000/mm3 AST/SGOT or ALT/SGPT >3.0 UNL 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 or Squamous cell carcinoma of the skin
  • Carcinoma in situ of the cervix or 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.

Seropositivity for human immunodeficiency virus at study entry Seropositivity for hepatitis C virus at study entry,

Active viral infection with hepatitis B virus at study entry:

  • HBsAg positive
  • HBsAg negative, anti-HBs positive and anti-HBc positive

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 criteria for randomization in maintenance phase:

  • SD or PD after induction treatment determined as per Cheson 1999 criteria
  • 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 of < 30 mL / min
  • ANC is < 1,000 cells/mm³
  • Platelet count is < 50,000 cells/mm³
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christine STEPHAN +33 4 72 66 93 33 christine.stephan@lysarc.org
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Netherlands,   Poland,   Portugal,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01865110
Other Study ID Numbers  ICMJE MCL R2 Elderly
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The Lymphoma Academic Research Organisation
Study Sponsor  ICMJE The Lymphoma Academic Research Organisation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Martin Dreyling, Prof. Dr. MCL Network
Principal Investigator: Vincent Ribrag, Dr Lymphoma Study Association
Principal Investigator: Johanna Cornelia Kluin-Nelemans, Prof. Dr. MCL Network
PRS Account The Lymphoma Academic Research Organisation
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP