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

NCT01516593 | Completed Phase 2

• 1 other identifier: CARMEN
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 8

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.

Conditions

HIV; Burkitt's Lymphoma

Keywords

HIV; Burkitt's lymphoma; intensive; short term; immuno-chemotherapy; HIV-positive patients with Burkitt's lymphoma

Outcome Measures

Primary Outcomes (1)

• evaluation of activity of the induction phase in terms of complete remission rate

  Objective lymphoma response achieved after the induction phase of the experimental treatment.

  at the end of the induction phase of the investigational intensive chemotherapy, an expected average of 45 days

Secondary Outcomes (4)

• Feasibility and tolerability of the investigational intensive chemotherapy in terms of grade ≥4 adverse events

  participants will be followed for the duration of the whole experimental program, an expected average of 100 days

• 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

  participants will be followed for the duration of the whole experimental program, an expected average of 100 days

• Feasibility and tolerability of intensification phase in terms of prevalence of grade ≥4 adverse events

  participants will be followed for the duration of the whole experimental program, an expected average of 100 days

• Activity of the whole investigational program in terms of complete remission rate

  at the end of the whole program, an expected average of 100 days

Study Arms (1)

intensive short term immuno-chemotherapy

EXPERIMENTAL

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

Drug: Induction Phase; Drug: Consolidation Phase (on day +50); Drug: Intensification phase; Drug: BEAM conditioning; Radiation: Consolidation radiotherapy

Interventions

Induction Phase 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

Also known as: Short-term intensive sequential chemoimmunotherapy

intensive short term immuno-chemotherapy

Consolidation Phase (on day +50) DRUG

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

Also known as: high-dose cytarabine; consolidation phase

intensive short term immuno-chemotherapy

Intensification phase 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).

Also known as: unresponsive patients, refractory disease

intensive short term immuno-chemotherapy

BEAM conditioning 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

Also known as: Conditioning regimen, autologous transplantation

intensive short term immuno-chemotherapy

Consolidation radiotherapy 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

Also known as: bulky irradiation; residual lesion

intensive short term immuno-chemotherapy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Andres J. M. Ferreri: lead

Study Sites (8)

Oncologia Medica A - Centro di Riferimento Oncologico

Aviano (PN), Italy

Location

Ematologia - A.O. Spedali Civili

Brescia, Italy

Location

Dip. Oncoematologia - Fondazione Centro San Raffaele del Monte Tabor

Milan, Italy

Location

S.C. Oncologia Medica - Ospedale San Paolo

Milan, Italy

Location

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

Milan, Italy

Location

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

Roma, Italy

Location

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

Terni, Italy

Location

U.O. Ematologia 2 - Ospedale San Giovanni Battista

Torino, Italy

Location

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

Cytarabine; Transplantation Conditioning; Transplantation, Autologous

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Transplantation; Surgical Procedures, Operative

Study Officials

• Andrés JM Ferreri, MD

  San Raffaele Scientific Institute, Milano, Italy

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 6, 2012
• First Posted: January 25, 2012
• Study Start: November 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: August 1, 2015
• Last Updated: August 4, 2022

Record last verified: 2022-08

Locations

IT (8)