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

January 6, 2012
January 24, 2012
November 2011
April 2013   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01516593 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Short Term Intensified Chemo-immunotherapy in HIV-positive Patients With Burkitt Lymphoma
Phase II Study on Safety and Activity of a Short Term Intensified Chemo-immunotherapy Combination in HIV-positive Patients Affected by Burkitt Lymphoma

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.

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%.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV
  • Burkitt's Lymphoma
  • 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
Experimental: intensive short term immuno-chemotherapy
Experimental treatment consists of an induction phase followed by a consolidation or intensified phase according to tumor response.
Interventions:
  • Drug: Induction Phase
  • Drug: Consolidation Phase (on day +50)
  • Drug: Intensification phase
  • Drug: BEAM conditioning
  • Radiation: Consolidation radiotherapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
19
August 2015
April 2013   (final data collection date for primary outcome measure)

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)
Both
18 Years to 60 Years
No
Contact: Andrés JM Ferreri, MD +39022643 ext 7649 ferreri.andres@hsr.it
Contact: Marta Bruno Ventre, MD +39022643 ext 7612 brunoventre.marta@hsr.it
Italy
 
NCT01516593
CARMEN
No
Andres J. M. Ferreri, IRCCS San Raffaele
Andres J. M. Ferreri
Not Provided
Study Chair: Andrés JM Ferreri, MD San Raffaele Scientific Institute, Milano, Italy
IRCCS San Raffaele
January 2012

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