Transplantation With Ybritumomab Tiuxetan (Zevalin) Plus BEAM Regimen in Patients With Refractory Large B-cell Difusse Lymphom (Z-BEAM LDGGB)

Autologous Transplantation of Haematopoietic Stem Cells With Conditioning Including Zevalin + BEAM to Patients Suffering From Refractory Large B-cell Diffuse Lymphom

To evaluate the efficacy (complete response rate) of Ybritumomab Tiuxetan (Zevalin) administration in the conditioning treatment of patients with refractory large B-cell diffuse lymphoma submitted to autologous transplantation of peripheral blood haematopoietic stem cells.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Ybritumomab Tiuxetan (Zevalin); Rituximab; BEAM (BCNU, ARAC, VP16 and Melphalan)

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain
    • Hospital Universitario de Alicante
  • Barcelona, Spain
    • H. de La Santa Creu I Sant Pau
  • Barcelona, Spain
    • Instituto Catalán de Oncología,
  • Córdoba, Spain
    • H. Reina Sofía
  • Madrid, Spain
    • H.U. La Princesa
  • Madrid, Spain
    • H.U. 12 de Octubre,
  • Madrid, Spain
    • H.U. Gregorio Marañón,
  • Madrid, Spain
    • H.U. La Paz
  • Madrid, Spain
    • Clínica Puerta de Hierro,
  • Madrid, Spain
    • M.D. Anderson Internacional
  • Murcia, Spain
    • H. Morales Messeguer
  • Murcia, Spain
    • H.U. Virgen de la Arrixaca
  • Salamanca, Spain
    • H. Clínico Universitario de Salamanca
  • Santander, Spain
    • H.U. Marqués de Valdecilla
  • Valencia, Spain
    • H.U. La Fe
  • Asturias
    • Oviedo, Asturias, Spain
      • H.U. Central de Asturias, Oviedo
  • Canarias
    • Santa Cruz de Tenerife, Canarias, Spain
      • H.Universitario de Canarias
  • Navarra
    • Pamplona, Navarra, Spain
      • Clinica Universitaria de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Give their written informed consent.

2. Abide by at least one of the following conditions:

   • Obtain no partial response after first-line chemotherapy including anthracyclines + rituximab (R-CHOP, R-MegaCHOP, R-EPOCH or the like), or else
   • Absence of partial response after having received salvage (post-induction) chemotherapy including R-IFE, R-ESHAP, R-ICE or the like.
   • Patients on first recidivation who do not attain partial remission after salvage chemotherapy.
   • Patients with transformed lymphoma, on first partial remission (No CR).
3. Stable disease at the time of transplantation.
4. Age ≥ 18 but ≤ 70.
5. Life expectancy of greater than three months.

Additionally, to be able to undergo haematopoietic stem cell transplantation, all patients should satisfy the requirements of routine clinical practice, i.e.:

1. Performance status (ECOG) < 3.
2. FEV1, DLCO and FVC ≥ 50% of the normal theoretical values.
3. Ventricular ejection fraction (through echocardiography or isotope ventriculography) ≥ 50%.
4. Total bilirubin and transaminases < 3 times the normal maximum value, except if attributable to the underlying disease.
5. Creatinine < 2 times the maximum normal value, and creatinine clearance > 40 ml/min, except if attributable to the underlying disease.
6. Absence of symptomatic heart disease, cirrhosis or active B or C virus hepatitis.
7. HIV negative.

Exclusion Criteria:

1. Impossibility of collecting, via apheresis, a number of CD34+ cells ≥ 2 x 106/kg.
2. Known hypersensitivity to mouse proteins.
3. Involvement of CNS by lymphoma.
4. Progressive lymphoma during the month prior to the date of transplantation.
5. Previous radioimmunotherapy.
6. Previous autologous transplantation of haematopoietic stem cells.
7. Pregnant or breastfeeding women, or adults of childbearing age who are not using an effective contraceptive method.
8. Being submitted to treatment in a clinical trial for 30 days prior to entry in this trial.
9. Active psychiatric disease, including addiction disorders.
10. Existence of active not-haematopoietic neoplasia, with the exception of cutaneous basal carcinoma or cervix intraepithelial carcinoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; BEAM preceded by Ybritumomab Tiuxetan (Zevalin)

Drug: Ybritumomab Tiuxetan (Zevalin); Rituximab; BEAM (BCNU, ARAC, VP16 and Melphalan); Day -21: rituximab. 250 mg/m2 iv Day -14: rituximab. 250 mg/m2 plus Ybritumomab Tiuxetan (Zevalin)(0.4 mCi/kg maximum dose 32 mCi). Days -6 to -1: BEAM regimen as follows BCNU: 300 mg/m2 over 2 hours, day -6. ARAC: 200 mg/m2/12 hours over 12 hours, days -5 through -2. VP16: 200 mg/m2/day over 2 hours, days -5 through -2. Melphalan: 140 mg/m2/day over 15 minutes, day -1.; Other Names: Rituximab (Mabthera); Ybritumomab Tiuxetan (Zevalin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease clinical response to treatment - complete response rate.	Pre-transplantation; post-transplantation (one week following Ybritumomab Tiuxetan (Zevalin) administration); And three months post-transplantation

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	96 months
Haematopoietic and extra-haematopoietic toxicity of the Ybritumomab Tiuxetan (Zevalin) plus BEAM regimen.	36 months
Overall response rate (complete + partial response)	36 month
Progression-free-survival	36 month
Post-transplantation haematological and immunological reconstitution	Until post-transplantation day +100

Collaborators and Investigators

• Sponsor: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
• Investigators: Principal Investigator: Dolores Caballero, MD, Hospital Clínico Universitario de Salamanca; Principal Investigator: Javier Briones, MD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: March 17, 2008
• First Submitted That Met QC Criteria: March 25, 2008
• First Posted (Estimate): March 28, 2008

Study Record Updates

• Last Update Posted (Estimate): February 15, 2016
• Last Update Submitted That Met QC Criteria: February 12, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Lymphoma; Autologous; GELTAMO; Z-BEAM
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Rituximab; Melphalan
• Other Study ID Numbers: GELTAMO-Z-BEAM LDGGB; EudraCT No.: 2007-003198 - 22