Short Term Intensified Chemo-immunotherapy in HIV-positive Patients With Burkitt Lymphoma (CARMEN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2012 by IRCCS San Raffaele
Sponsor:
Information provided by (Responsible Party):
Andres J. M. Ferreri, IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT01516593
First received: January 6, 2012
Last updated: January 24, 2012
Last verified: January 2012
  Purpose

This is a multicenter,open-label trial to evaluate activity and safety of the investigational intensive in HIV+ patients with Burkitt's lymphoma.

Experimental treatment consists of an induction phase followed by a consolidation or intensified phase according to tumor response.

Until recently, the immuno-compromised state of patients with concomitant HIV/AIDS and BL was thought to limit the ability to administer intensive chemotherapeutic regimens due to infection rate. However, the advent of highly active antiretroviral therapy (HAART) and evidence in diffuse large B-cell lymphomas that HIV-positive patients can tolerate standard chemotherapeutic regimens with improved outcomes have led investigators to treat HIV-positive patients with the same intensive chemotherapy regimens used to treat immuno-competent patients. Data suggest that these current approaches, along with supportive care, may result in improved patient outcomes, similar to those in the immuno-competent patient population.


Condition Intervention Phase
HIV
Burkitt's Lymphoma
Drug: Induction Phase
Drug: Consolidation Phase (on day +50)
Drug: Intensification phase
Drug: BEAM conditioning
Radiation: Consolidation radiotherapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study on Safety and Activity of a Short Term Intensified Chemo-immunotherapy Combination in HIV-positive Patients Affected by Burkitt Lymphoma

Resource links provided by NLM:


Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • evaluation of activity of the induction phase in terms of complete remission rate [ Time Frame: at the end of the induction phase of the investigational intensive chemotherapy, an expected average of 45 days ] [ Designated as safety issue: Yes ]
    Objective lymphoma response achieved after the induction phase of the experimental treatment.


Secondary Outcome Measures:
  • Feasibility and tolerability of the investigational intensive chemotherapy in terms of grade ≥4 adverse events [ Time Frame: participants will be followed for the duration of the whole experimental program, an expected average of 100 days ] [ Designated as safety issue: Yes ]
    Assessment of incidence of grade 4 AE during experimental treatment (induction, consolidation and intensification phases as well as conditioning and autologous stem cell transplantation (if indicated)

  • Feasibility and tolerability of the consolidation phase followed by BEAM conditioning and autologous stem cell transplantation in terms of prevalence of grade ≥4 adverse events [ Time Frame: participants will be followed for the duration of the whole experimental program, an expected average of 100 days ] [ Designated as safety issue: Yes ]
  • Feasibility and tolerability of intensification phase in terms of prevalence of grade ≥4 adverse events [ Time Frame: participants will be followed for the duration of the whole experimental program, an expected average of 100 days ] [ Designated as safety issue: Yes ]
    Participants who will not achieve a complete or partial response after induction and consolidation phases will be referred to intensification phase, which will be followed by BEAM + ASCT. These patients will be assess for tolerabbility and AE during these therapeutic phases.

  • Activity of the whole investigational program in terms of complete remission rate [ Time Frame: at the end of the whole program, an expected average of 100 days ] [ Designated as safety issue: Yes ]
    Participants will be assessed by conventional exams to define complete remission rate after the whole experiemntal program; that is after consolidation phase for patients who achieved complete remission after induction phase, after BEAM + ASCt for patients who achieved partial response after induction phase, and after intensification phase for patients who did not achieve an objective response after induction phase.


Estimated Enrollment: 19
Study Start Date: November 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: intensive short term immuno-chemotherapy
Experimental treatment consists of an induction phase followed by a consolidation or intensified phase according to tumor response.
Drug: Induction Phase
  • dd -2 to 1: Methylprednisolone
  • dd 0-1, Cyclophosphamide, associated on day 0 with Vincristine
  • dd 2, Rituximab
  • dd 7, Methotrexate
  • dd 14, Rituximab
  • dd 15, Etoposide
  • dd 21, Methotrexate
  • dd 29, Rituximab and Doxorubicin
  • dd 36, Rituximab and VCR

At the end of this induction phase, subsequent treatment will be performed according to the objective response:

  1. pts in CR: consolidation phase followed by bulky site irradiation
  2. pts in PR: consolidation phase followed by BEAM conditioning regimen supported by ASCT and bulky irradiation
  3. pts with SD after induction or PD during or after induction: intensification phase followed by BEAM conditioning regimen supported by ASCT and bulky irradiation
Other Name: Short-term intensive sequential chemoimmunotherapy
Drug: Consolidation Phase (on day +50)
  • dd 1-2: cytarabine twice a day
  • dd 3 and 11: rituximab
  • dd 11-13: leukapheresis for PBPC collection.
Other Name: high-dose cytarabine; consolidation phase
Drug: Intensification phase
  1. One or two courses of R-IVAC or R-ICE chemoimmunotherapy regimen, every three weeks as debulking.
  2. CTX (dd 1) associated with rituximab on dd 3 and 10, followed by PBPC collection (dd 11-13);
  3. AraC every 12 hours for four days (dd -5 to -2) supported by reinfusion of CD34+ cells (dd 0), rituximab infusion (dd -1 and +11) and second in-vivo purged PBPC collection (if needed).
Other Name: unresponsive patients, refractory disease
Drug: BEAM conditioning
BCNU on dd 1; VP-16 every 12 hours on dd 2-5 and araC every 12 hours on dd 2-5; melphalan on dd 6, followed by the reinfusion of CD34+ cells
Other Name: Conditioning regimen, autologous transplantation
Radiation: Consolidation radiotherapy
At the end of the whole program, patients will be evaluated for involved-field irradiation with 6-10 MeV photons and a dose of 36 Gy (2 Gy/d, five fractions a week). Three subgroups of patients will be considered for radiotherapy
Other Name: bulky irradiation; residual lesion

Detailed Description:

The activity of feasibility of the proposed program will be assessed in HIV+ patients with Burkitt lymphoma with the aim to improve tolerability, minimize source consuming and supporting treatment and redu ce late sequels. Available combinations in this setting are really source demanding and toxic combinations showing high rates of septic complication and a treatment-related mortality of near 20%.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic diagnosis of Burkitt's lymphoma (WHO 2008)
  • HIV sero-positivity
  • Age ≥18 and ≤60 years
  • ECOG-PS ≤3

Exclusion Criteria:

  • CNS parenchymal involvement
  • Absolute neutrophil count <1.000 cells/μL and platelets count <75 × 109/L (Burkitt unrelated)
  • Creatinine >1,5N (Burkitt unrelated)
  • SGOT and/or SGTP >2,5N (Burkitt unrelated)
  • Bilirubin >2N (Burkitt unrelated)
  • Severe psychiatric illness or any other clinical, social or psychological condition that could interfere with patient's adherence and compliance
  • Significant cardiac disease or acute myocardial infarction in the last 12 months
  • Severe active infection (except for HBV and/or HCV co-infection)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01516593

Contacts
Contact: Andrés JM Ferreri, MD +39022643 ext 7649 ferreri.andres@hsr.it
Contact: Marta Bruno Ventre, MD +39022643 ext 7612 brunoventre.marta@hsr.it

Locations
Italy
Oncologia Medica A - Centro di Riferimento Oncologico Not yet recruiting
Aviano (PN), Italy
Contact: Michele Spina, MD    +300434659 ext 284    mspina@cro.it   
Principal Investigator: Michele Spina, MD         
Ematologia - A.O. Spedali Civili Not yet recruiting
Brescia, Italy
Contact: Alessandro Re, MD    +39030399 ext 5438    sandrore@aruba.it   
Principal Investigator: Alessandro Re, MD         
Dip. Oncoematologia - Fondazione Centro San Raffaele del Monte Tabor Recruiting
Milano, Italy
Contact: Andrés JM Ferreri, MD    +39022643 ext 7649    ferreri.andres@hsr.it   
Contact: Marta Bruno Ventre, MD       brunoventre.marta@hsr.it   
Principal Investigator: Andrés JM Ferreri, MD         
S.C. Oncologia Medica - Ospedale San Paolo Not yet recruiting
Milano, Italy
Contact: Niccolò Frungillo, MD       niccolo.frungillo@ao.sanpaolo.it   
Principal Investigator: Niccolò Frungillo, MD         
S.C. Oncologia Medica 3 - IRCCS Istituto Nazionale Tumori (INT) Not yet recruiting
Milano, Italy
Contact: Massimo Di Nicola, MD    +39022390 ext 2360    massimo.dinicola@istitutotumori.mi.it   
Principal Investigator: Massimo Di Nicola, MD         
U.O.C. Immunodeficienze virali - I.N.M.I. L. Spallanzani Not yet recruiting
Roma, Italy
Contact: Andrea Antinori, MD    +390655170 ext 348    andrea.antinori@inmi.it   
Principal Investigator: Andrea Antinori, MD         
S.C. Oncoematologia - A.O. Santa Maria Not yet recruiting
Terni, Italy
Contact: Anna Marina Liberati, MD    +390744205 ext 971    marinal@unipg.it   
Principal Investigator: Anna Marina Liberati, MD         
U.O. Ematologia 2 - Ospedale San Giovanni Battista Not yet recruiting
Torino, Italy
Contact: Dino Allione, MD    +39011633 ext 6685    ballione@molinette.piemonte.it   
Principal Investigator: Dino Allione, MD         
Sponsors and Collaborators
Andres J. M. Ferreri
Investigators
Study Chair: Andrés JM Ferreri, MD San Raffaele Scientific Institute, Milano, Italy
  More Information

No publications provided

Responsible Party: Andres J. M. Ferreri, MD, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT01516593     History of Changes
Other Study ID Numbers: CARMEN
Study First Received: January 6, 2012
Last Updated: January 24, 2012
Health Authority: Italy: Ethics Committee
Italy: The Italian Medicines Agency

Keywords provided by IRCCS San Raffaele:
HIV
Burkitt's lymphoma
intensive
short term
immuno-chemotherapy
HIV-positive patients with Burkitt's lymphoma

Additional relevant MeSH terms:
Burkitt Lymphoma
HIV Seropositivity
Lymphoma
DNA Virus Infections
Epstein-Barr Virus Infections
Herpesviridae Infections
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Immunoproliferative Disorders
Lentivirus Infections
Lymphatic Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Experimental
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Tumor Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014