R-BMD in Refractory or Relapsed Lymphoma, GELTAMO Clinical Trial

Study Phase II Non-randomized Prospective Open to Assess the Combination of Rituximab, Bendamustine, Mitoxantrone, Dexamethasone (R-BMD) in Patients With Follicular Lymphoma Refractory or Relapsed

Assess the combination of efficacy of the combination of rituximab, bendamustine, mitoxantrone, dexamethasone in the treatment of patients with Follicular Lymphoma.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Rituximab, Bendamustine, Mitoxantrone, Dexamethasone

Detailed Description

Assess the combination of efficacy and safety of the combination of rituximab, bendamustine, mitoxantrone, dexamethasone in the treatment of patients with Follicular Lymphoma who are refractory or in relapse.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruna
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Barcelona, Spain, 08035
    • Hospital Vall D´Hebron
  • Bilbao, Spain, 48013
    • Hospital de Basurto
  • Cáceres, Spain, 10002
    • Hospital San Pedro Alcántara
  • Cádiz, Spain, 11009
    • Hospital Puerta del Mar
  • Jaén, Spain, 23007
    • Hospital de Jaen
  • Madrid, Spain, 28009
    • Hospital Gregorio Marañón
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Murcia, Spain, 30008
    • Hospital Morales Meseguer
  • Málaga, Spain, 29010
    • Complejo Hospitalario Carlos Haya
  • Salamanca, Spain, 37007
    • Hospital de Salamanca
  • Segovia, Spain, 42002
    • Hospital General de Segovia
  • Sevilla, Spain, 41013
    • Hospital Virgen Del Rocio
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46015
    • Hospital Arnau De Vilanova
  • Valencia, Spain, 46014
    • Hospital General de Valencia
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • Valladolid, Spain, 47012
    • Hospital Rio Hortega
  • Zamora, Spain, 49022
    • Hospital Virgen de la Concha
  • Zaragoza, Spain, 50009
    • Hospital Miguel Servet
  • Zaragoza, Spain, 50009
    • Hospital Clínico de Zaragoza
  • A Coruña
    • Santiago, A Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago
  • Alava
    • Vitoria, Alava, Spain, 01009
      • Hospital Txagorritxu
  • Alicante
    • San Juan de Alicante, Alicante, Spain, 03550
      • Hospital San Juan de Alicante
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol
  • Bilbao
    • Galdakao, Bilbao, Spain, 48960
      • Hospital de Galdakao
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Marques de Valdecilla
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain, 11407
      • Hospital de Jerez
  • Madrid
    • Alcorcón, Madrid, Spain, 289222
      • Hospital Fundación de Alcorcón
    • Getafe, Madrid, Spain, 28901
      • Hospital de Getafe
    • Leganés, Madrid, Spain, 28911
      • Hospital Severo Ochoa
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Puerta de Hierro
  • Mallorca
    • Palma de Mallorca, Mallorca, Spain, 07010
      • Hospital Son Llatzer
    • Palma de Mallorca, Mallorca, Spain, 07014
      • Hospital Son Espases
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Universitario Virgen de Arrixaca
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria De Navarra
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 and ≤ 75 years.
2. Patients with follicular lymphoma grade 1, 2 or 3a, CD20 +, histologically confirmed lymph node biopsy or tissue. Be accepted diagnosis in bone marrow if no accessible lymph nodes and whether it has discarded the mantle LLC, and NHL.
3. Follicular lymphoma patients treated with the combination of rituximab and chemotherapy in first line, which have been refractory or relapsed after having achieved any responses to this first line of pretreatment (excluding radiotherapy).
4. ECOG ≤ 2.
5. Signed written informed consent.

Exclusion Criteria:

1. Clinical suspicion or documentation of histological transformation.
2. Have received prior chemotherapy scheme, first line without Rituximab.
3. Prior autologous or allogeneic.
4. CNS infiltration by LF (primary CNS lymphoma or lymphomatous meningitis).
5. Past or active Hepatitis B (at least one of the following markers HBsAg, HBe Ag, anti-HBc, HBV DNA)
6. HCV infection. HIV infection or other conditions of serious immunosuppression.
7. Previous neoplasms except non-melanoma skin cancer of the cervix or adequately treated.
8. Cardiac function in cardiac patient known or prior treatment with anthracyclines with EF <50%.
9. Impaired renal function (creatinine> 1.5 x Upper Limit of Normal, LSN) or a creatinine clearance <50 ml / h, not related to lymphoma.
10. Impaired liver function (bilirubin, AST / ALT or GGT> 2 x ULN) were not related to lymphoma.
11. Women who are nursing or pregnant. Women of childbearing potential will be included prior pregnancy test serum / urine negative. Use effective contraception to be kept for 1 year after cessation of rituximab.
12. Patients with heart disease, pulmonary, neurological, psychiatric or severe metabolic and not secondary to lymphoma.
13. Severe acute or chronic infection in activity.
14. Any other concurrent medical or psychological comorbidity that might interfere with participation in this study.

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: R-BMD; Rituximab, Bendamustine, Mitoxantrone, Dexamethasone Induction: 6 Rituximab, Bendamustine, Mitoxantrone, Dexamethasone cycles Maintenance: Rituximab every 3 months for 2 years	Drug: Rituximab, Bendamustine, Mitoxantrone, Dexamethasone; Bendamustine: 90 mg/m2/day, days 1 and 2 of each cycle, iv Mitoxantrone: 6 mg/m2/day, day 1 of each cycle, iv Dexamethasone 20 mg / day, days 1 through 5 of each cycle, od Rituximab: 375 mg / m 2 / day, day 1 of each cycle, iv; Other Names: R-BMD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	The primary endpoint is the number of Participants with Response according to the criteria of the International Workshop to Standardize Response Criteria for NHL Complete Remission (CR): Nodes returned to normal (if GTD >15 mm before therapy, GTD now ≤15 mm; if GTD 11-15 and SA >10 mm before therapy, SA now ≤10 mm) All (non-nodal) target lesions completely resolved Partial Remission (PR) SPD of target lesions decreased ≥50% from baseline Spleen and liver nodules regress by 50% in SPD or single lesion in GTD Stable Disease (SD) Not enough shrinkage for PR Not enough growth for PD Progressive Disease (PD): SPD increase ≥50% from nadir (smallest value seen during trial) in nodal target lesions overall or in any single nodal target lesion	7 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary Endpoints Included an Assessment of the Following Parameters: Progression-Free Survival, Disease-Free Survival, Global Survival, Duration of the Response.	7 years

Collaborators and Investigators

• Sponsor: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
• Investigators: Principal Investigator: Fátima de la Cruz, MD, Hospital Virgen Del Rocio; Principal Investigator: Andrés López Hernández, MD, Hospital Vall D´Hebron; Principal Investigator: Carlos Montalbán Sanz, MD, Hospital Universitario Ramón y Cajal; Principal Investigator: Juan Manuel Sancho Cia, MD, Germans Trias i Pujol Hospital; Principal Investigator: Miguel Ángel Canales Albendea, MD, Hospital La Paz; Principal Investigator: Roberto Hernández Martín, MD, Hospital Virgen de la Concha; Principal Investigator: Elena Pérez Ceballos, MD, Hospital Morales Meseguer; Principal Investigator: Eulogio Conde García, MD, Hospital Marques de Valdecilla; Principal Investigator: Francisco Javier Peñalver Párraga, MD, Hospital Universitario Fundacion Alcorcon; Principal Investigator: Javier De la Serna Torroba, MD, Hospital 12 de Octubre; Principal Investigator: Francisca Oña Compan, MD, Hospital de Getafe.; Principal Investigator: Patricia Font López, MD, Gregorio Maranon Hospital; Principal Investigator: Secundino Ferrer Bordas, MD, Hospital Dr. Peset; Principal Investigator: José Ramón Mayans Ferrer, MD, Hospital Arnau De Vilanova; Principal Investigator: José Antonio Márquez Navarro, MD, Hospital de Basurto; Principal Investigator: Ernesto Pérez Persona, MD, Hospital Txagorritxu; Principal Investigator: Garazi Letamendi Madariaga, MD, Hospital de Galdakao; Principal Investigator: Pilar Giraldo Castellanos, MD, Hospital Miguel Servet; Principal Investigator: Luis Palomera Bernal, MD, Hospital Clínico de Zaragoza; Principal Investigator: Blanca Sánchez González, MD, Hospital del Mar; Principal Investigator: José Luis Sánchez-Majado, MD, Hospital San Juan de Alicante; Principal Investigator: Antonio Gutiérrez García, MD, Hospital Son Espases; Principal Investigator: Francisco Javier Capote Huelva, MD, Hospital Universitario Puerta Del Mar; Principal Investigator: Mª José Ramírez, MD, Hospital de Jerez; Principal Investigator: Fernando Carnicero González, MD, Hospital San Pedro de Alcantara; Principal Investigator: Mª José Rodríguez Salazar, MD, Hospital Universitario de Canarias; Principal Investigator: José Antonio García Marco, MD, Hospital Puerta de Hierro; Principal Investigator: Rosalía Riaza Grau, MD, Hospital Severo Ochoa; Principal Investigator: Mª Dolores Caballero Barrigón, MD, Hospital de Salamanca; Principal Investigator: Mª Jesús Peñarrubia Ponce, MD, Hospital Rio Hortega; Principal Investigator: José Antonio Queizán, MD, Hospital de Segovia; Principal Investigator: Mª José Terol Castera, MD, Hospital Clinico de Valencia; Principal Investigator: Félix Carbonell, MD, Hospital General Universitario de Valencia; Principal Investigator: María Rosario Varela Gómez, MD, Complejo Hospitalario A Coruña; Principal Investigator: José Luis Bello López, MD, C. H. U. Santiago; Principal Investigator: Carlos Panizo, MD, Clinica Universitaria De Navarra; Principal Investigator: Armando López Guillermo, MD, Hospital Clinic I Provincial; Principal Investigator: Andrés Sánchez Salinas, MD, Hospital Universitario Virgen de La Arrixaca; Principal Investigator: Mª Soledad Durán Nieto, MD, Hospital de Jaen; Principal Investigator: Manuel Espeso de Haro, MD, Hospital Carlos Haya; Principal Investigator: Joan Bargay Lleonart, MD, Hospital Son Llatzer

Publications and helpful links

General Publications

• Penalver FJ, Marquez JA, Duran S, Giraldo P, Martin A, Montalban C, Sancho JM, Ramirez MJ, Terol MJ, Capote FJ, Gutierrez A, Sanchez B, Lopez A, Salar A, Rodriguez-Caravaca G, Canales M, Caballero MD; GELTAMO (The Spanish Lymphoma Cooperative Group). Response-adapted treatment with rituximab, bendamustine, mitoxantrone, and dexamethasone followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma after first-line immunochemotherapy: Results of the RBMDGELTAMO08 phase II trial. Cancer Med. 2019 Nov;8(16):6955-6966. doi: 10.1002/cam4.2555. Epub 2019 Oct 1.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: February 11, 2010
• First Submitted That Met QC Criteria: May 27, 2010
• First Posted (Estimate): May 28, 2010

Study Record Updates

• Last Update Posted (Actual): November 1, 2018
• Last Update Submitted That Met QC Criteria: February 21, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Follicular non-Hodgkin's lymphoma relapse refractory
• 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; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Dexamethasone; Bendamustine Hydrochloride; Rituximab; Mitoxantrone
• Other Study ID Numbers: R-BMD GELTAMO 08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED