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

Sponsor

Andres J. M. Ferreri (Other)

Overall Status

Completed

CT.gov ID

NCT01516593

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

2.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	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

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%.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Apr 1, 2013

Actual Study Completion Date :

Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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: pts in CR: consolidation phase followed by bulky site irradiation pts in PR: consolidation phase followed by BEAM conditioning regimen supported by ASCT and bulky irradiation 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 Names: 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 Names: high-dose cytarabine; consolidation phase Drug: Intensification phase One or two courses of R-IVAC or R-ICE chemoimmunotherapy regimen, every three weeks as debulking. CTX (dd 1) associated with rituximab on dd 3 and 10, followed by PBPC collection (dd 11-13); 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 Names: 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 Names: 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 Names: bulky irradiation; residual lesion

Arm

Intervention/Treatment

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: pts in CR: consolidation phase followed by bulky site irradiation pts in PR: consolidation phase followed by BEAM conditioning regimen supported by ASCT and bulky irradiation 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 Names:

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 Names:

high-dose cytarabine; consolidation phase

Drug: Intensification phase

One or two courses of R-IVAC or R-ICE chemoimmunotherapy regimen, every three weeks as debulking. CTX (dd 1) associated with rituximab on dd 3 and 10, followed by PBPC collection (dd 11-13); 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 Names:

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 Names:

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 Names:

bulky irradiation; residual lesion

Outcome Measures

Primary Outcome Measures

evaluation of activity of the induction phase in terms of complete remission rate [at the end of the induction phase of the investigational intensive chemotherapy, an expected average of 45 days]
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 [participants will be followed for the duration of the whole experimental program, an expected average of 100 days]
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 [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]
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 [at the end of the whole program, an expected average of 100 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country
1	Oncologia Medica A - Centro di Riferimento Oncologico	Aviano (PN)	Italy
2	Ematologia - A.O. Spedali Civili	Brescia	Italy
3	Dip. Oncoematologia - Fondazione Centro San Raffaele del Monte Tabor	Milano	Italy
4	S.C. Oncologia Medica - Ospedale San Paolo	Milano	Italy
5	S.C. Oncologia Medica 3 - IRCCS Istituto Nazionale Tumori (INT)	Milano	Italy
6	U.O.C. Immunodeficienze virali - I.N.M.I. L. Spallanzani	Roma	Italy
7	S.C. Oncoematologia - A.O. Santa Maria	Terni	Italy
8	U.O. Ematologia 2 - Ospedale San Giovanni Battista	Torino	Italy