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

NCT ID: NCT01516593

Last Updated: 2022-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2015-08-31

Brief Summary

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.

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%.

Conditions

HIV; Burkitt's Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intensive short term immuno-chemotherapy

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

Group Type: EXPERIMENTAL

Induction Phase

Intervention Type: DRUG

• 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

Consolidation Phase (on day +50)

Intervention Type: DRUG

• dd 1-2: cytarabine twice a day
• dd 3 and 11: rituximab
• dd 11-13: leukapheresis for PBPC collection.

Intensification phase

Intervention Type: DRUG

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).

BEAM conditioning

Intervention Type: DRUG

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

Consolidation radiotherapy

Intervention Type: RADIATION

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

Interventions

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

Intervention Type: 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.

Intervention Type: 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).

Intervention Type: 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

Intervention Type: DRUG

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

Intervention Type: RADIATION

Other Intervention Names

Short-term intensive sequential chemoimmunotherapy; high-dose cytarabine; consolidation phase; unresponsive patients, refractory disease; Conditioning regimen, autologous transplantation; bulky irradiation; residual lesion

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Andres J. M. Ferreri

OTHER

Sponsor Role: lead

Responsible Party

Andres J. M. Ferreri

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Andrés JM Ferreri, MD

Role: STUDY_CHAIR

San Raffaele Scientific Institute, Milano, Italy

Locations

Oncologia Medica A - Centro di Riferimento Oncologico

Aviano (PN), , Italy

Ematologia - A.O. Spedali Civili

Brescia, , Italy

Dip. Oncoematologia - Fondazione Centro San Raffaele del Monte Tabor

Milan, , Italy

S.C. Oncologia Medica - Ospedale San Paolo

Milan, , Italy

S.C. Oncologia Medica 3 - IRCCS Istituto Nazionale Tumori (INT)

Milan, , Italy

U.O.C. Immunodeficienze virali - I.N.M.I. L. Spallanzani

Roma, , Italy

S.C. Oncoematologia - A.O. Santa Maria

Terni, , Italy

U.O. Ematologia 2 - Ospedale San Giovanni Battista

Torino, , Italy

Countries

Italy

Other Identifiers

CARMEN

Identifier Type: -

Identifier Source: org_study_id