Rituximab and DexaBEAM as Salvage Therapy for Relapsed Lymphoma
Condition: Relapsed Non-Hodgkin-Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 2

Summary: 
      The investigator prospectively evaluated the combination of Rituximab and Dexa-BEAM
      (dexamethasone, carmustine, etoposide, cytarabine, melphalan) followed by high dose therapy
      in patients with relapsed/refractory aggressive and indolent lymphoma.
    

Detailed description: 
      This study was a prospective, open label, single arm multicenter phase II study. It was
      approved by the ethics committees of the participating centers, and all regulatory issues and
      the principles of GCP were followed. The study was initiated in 2002, and recruitment closed
      in 2006. Final data analysis was performed in 3/2013. The trial had been registered at the
      clinical trial database of the CIMT consortium The overall treatment plan in brief, eligible
      patients were treated with two cycles of R-DexaBEAM in a 3-4 week interval, and stem cell
      mobilization was scheduled after the second cycle. Mobilization after the first cycle was
      allowed if the patient had received extensive prior therapy and if no evidence of
      BM-involvement was found. HDT was scheduled within 4-8 weeks after the last R-DexaBEAM cycle
      in patients achieving at least PR.

      Protocols: The applied chemotherapy protocols were as follows: The
      salvage/mobilization-regimen consisted of R-DexaBEAM: Rituximab 375mg/m² d1, dexamethasone 24
      mg t.i.d p.o., d 1-10; BCNU 60mg/m² i.v., d 2; etoposide 75mg/m² i.v., d 4-7; cytarabin
      200mg/m² b.i.d i.v., d 4-7 in 2 doses; melphalan 20mg/m² i.v., d3. For high dose
      radio/chemotherapy, two different conditioning regimens were defined in the protocol:
      chemo-radiotherapy R-TBI/Cy consisted of Rituximab 375mg/m² i.v. d -7, -2, fractionated total
      body irradiation with 12 Gy, d -6 to -4; and cyclophosphamide 60 mg/kgbw i.v., day -3 to -2.

      The chemotherapy protocol used for conditioning was R-BEAM: Rituximab 375mg/m² i.v. d -8, -2,
      BCNU 300mg/m² i.v., d -7; cytarabin 400mg/m² b.i.d. i.v., d -6 to -3; etoposide 200mg/m² i.v.
      b.i.d., d -6 to -3; melphalan 140mg/m² i.v., d -2.

      Stem cell mobilization: Following mobilization chemotherapy, stem cells were collected after
      G-CSF stimulation (5-10µg/kg bw/d, starting on day 11 after R-DexaBEAM) using standard
      apheresis procedures, and stem cells were processed and cryopreserved according to local
      standards. A minimum number of 2x106/kgbw CD34 positive cells were required for the conduct
      of high dose therapy.

      Autologous stem cell transfusion: For stem cell rescue after HDT, at least 2x106/kg CD34
      positive cells were applied. Stem cells were thawed at bedside and infused via central venous
      catheter.

      Concomitant treatments were conducted according to local standards, e.g. for antiemetic
      prophylaxis, hydration and parenteral nutrition. At the time of trial initiation, a
      prophylactic antibiotic treatment was recommended due to local standards, e.g. ciprofloxacin.
      For PJP prophylaxis co-trimoxazole was mandatory until recovery to a CD4-cell count of 200/µl
      had been reached or until day 100 post stem cell re-transfusion. In cases of symptomatic
      CMV-reactivation, treatment with ganciclovir was recommended. In addition, maintenance of
      immunoglobulin levels at concentrations >5g/l was recommended. G-CSF support was optional
      after salvage or high dose therapy (5µg/kgbw).

      Diagnostic evaluation: Throughout the entire treatment, routine laboratory investigations
      were performed. In addition, CMV-reactivation screening was mandatory in CMV positive
      patients. staging procedures including CT-scans were scheduled at baseline, prior to HDT and
      2, 6, 9, 12, 18, 24, 36 months after HDT, and thereafter as clinically indicated. Responses
      were assessed using the criteria of Cheson et al. BM was evaluated at baseline, and
      re-evaluation was only needed to confirm complete remission.

      Statistical analysis The primary efficacy endpoint of the study was progression-free survival
      (PFS), as calculated for the intent-to-treat population. Event-free survival was defined as
      the time from the date of trial inclusion to the time of either disease progression or death
      (irrespective of cause) or the latest follow-up without progression.

      Secondary efficacy endpoints were overall response rate at day 60 post stem cell
      re-transfusion, overall survival (time from inclusion to death, irrespective of cause),
      safety and side effects, toxicity of high dose therapy according to Bearman score, and number
      of CMV-reactivations. Further endpoints, which will be reported separately, were the
      percentage of patients being negative for minimal residual disease (MRD) by either t(14;18) -
      FL or t(11;14) - MCL PCR, time to immune reconstitution with achievement of a CD4 count of
      200/µl.

      Results for time-to-event endpoints were analysed according to Kaplan-Meier estimator, and
      comparisons were performed with the log-rank test. P <0.05 was considered statistically
      significant. GraphPad Prism version 5.0 for Windows, (GraphPad Software, CA, USA) was used
      for all calculations. Statistical advice was given by the Institute of Epidemiology and
      Biometrical Statistics at the University of Mainz.
    

Intervention name(s): Rituximab and DexaBEAM
Intervention type(s): Drug
Intervention description(s): combination treatment
Other intervention name(s): Rituxan
Intervention MeSH terms: Rituximab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: lymphoma; high dose therapy; DexaBEAM; Rituximab; role of alternative salvage treatment - dexaBEAM