Prospective Multicenter Dose Finding Phase II Pilot Trial to Evaluate Efficacy and Safety of LR-CHOP21 for Elderly Patients With Untreated Diffuse Large B Cell Lymphoma

NCT ID: NCT00907348

Last Updated: 2011-10-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-31

Study Completion Date

2012-01-31

Brief Summary

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This is a prospective multicenter phase II pilot trial designed with the purpose of dose finding to evaluate the efficacy and safety of treatment with Lenalidomide plus R-CHOP21 (LR-CHOP21) for elderly patients with untreated Diffuse Large B Cell Lymphoma (DLBCL).

Detailed Description

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Conditions

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Non Hodgkin Lymphoma Follicular Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohorts 1 - 2 - 3 - 4

Chemiotherapy

Group Type EXPERIMENTAL

LR-CHOP21

Intervention Type DRUG

FIRST DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1; Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 5 mg/day D1-D14

SECOND DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1;Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 10 mg/day D1-D14

THIRD DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1; Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 15 mg/day D1-D14

FOURTH DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1; Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 20 mg/day D1-D14 Repeated every 21 days

Interventions

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LR-CHOP21

FIRST DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1; Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 5 mg/day D1-D14

SECOND DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1;Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 10 mg/day D1-D14

THIRD DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1; Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 15 mg/day D1-D14

FOURTH DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1; Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 20 mg/day D1-D14 Repeated every 21 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Understand and voluntarily sign an informed consent form
2. Able to adhere to the study visit schedule and other protocol requirements
3. Histologic subtypes as follows:

* CD20 positive Diffuse large B-Cell lymphoma
* CD20 positive Follicular grade IIIb
4. Age 60-80
5. Untreated patients. In patients with bulky mass or systemic symptoms or compressive disease or rapidly progressive adenopathies a pre-study treatment is allowed with steroids and/or a single dose of Vincristine 1.4 mg/mq (max 2) in the seven days prior the start of the study treatment
6. Measurable and/or evaluable disease
7. Ann Arbor stage II, III, IV
8. International Prognostic Index at low-intermediate, intermediate-high, high risk (2/3/4-5)
9. Adequate haematological counts: ANC \> 1.5 x 109/L and platelet count \> 75 x 109/L unless due to bone marrow involvement
10. Conjugated bilirubin up to 2 x UNL
11. Alkaline phosphatase and transaminases up to 2 x UNL
12. Creatinine clearance \> 50 ml/min
13. HIV negativity
14. HCV negativity
15. HBV negativity or patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative
16. Cardiac ejection fraction (MUGA scan or echocardiography) \> 45%
17. Non peripheral neuropathy or CNS disease. Non testicular Lymphoma
18. Life expectancy \> 6 months
19. Performance status \< 2 according to ECOG scale
20. Comprehensive geriatric assessment (CGA) as outlined in Appendix 15 showing absence of any impairment in activity of daily living (ADL), of any condition defining a geriatric syndrome, and of any grade 4 comorbidity or of more than three grade 3 comorbidities according to CIRS-G scale
21. Disease free of prior malignancies for ≥ 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
22. Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: for at least 28 days before starting study drug;while participating in the study; for at least 28 days after discontinuation from the study

* The two methods of reliable contraception must include one highly effective method (i.e., intrauterine device (IUD), hormonal \[birth control pills, injections, or implants\], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e., latex condom, diaphragm, cervical cap)
* FCBP must be referred to a qualified provider of contraceptive methods if needed

Exclusion Criteria

1. Lymphoblastic Lymphoma
2. Burkitt Lymphoma
3. Non Hodgkin lymphoma CD 20 negative
4. Mantle Cell Lymphoma
5. Follicular Non Hodgkin Lymphoma grade I-II-IIIa
6. Primitive mediastinal diffuse large B cell lymphoma with only mediastinal involvement
7. International Prognostic Index at low risk (1)
8. Has known or suspected hypersensitivity or intolerance to Rituximab
9. History of evolutive malignancy within the last 3 years other than squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast
10. Extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy before enrollment within 3 years before the start of treatment
11. Exposure to Rituximab prior to study entry
12. Have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study
13. CNS disease (meningeal and/or brain involvement by lymphoma) or Testicular involvement
14. DVT in the last year
15. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
16. Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug
17. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 5, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
18. Creatinine clearance \< 50 ml/min
19. Presence of major neurological disorders
20. HIV positivity
21. HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative
22. HCV positivity
23. Active opportunistic infection
24. Comprehensive geriatric assessment (CGA) as outlined in Appendix 15 showing presence of any impairment in activity of daily living (ADL), of any condition defining a geriatric syndrome, and of any grade 4 comorbidity or of more than three grade 3 comorbidities according to CIRS-G scale
25. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
Minimum Eligible Age

60 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

OTHER

Sponsor Role collaborator

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Umberto Vitolo, MD

Role: STUDY_DIRECTOR

Azienda Sanitaria Ospedaliera-Universitaria S. Giovanni Battista - TORINO

Locations

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Divisione di Ematologia Osp. SS. Antonio e Biagio

Alessandria, , Italy

Site Status

Divisione di Oncologia Medica A Centro di Riferimento Oncologico

Aviano, , Italy

Site Status

Cattedra di Ematologia Università Policlinico

Bari, , Italy

Site Status

IRCCS Istituto Tumori Giovanni Paolo II

Bari, , Italy

Site Status

Istituto di Ematologia "Seragnoli" Polic.S.Orsola-Malpighi

Bologna, , Italy

Site Status

Divisione di Ematologia Spedali Civili

Brescia, , Italy

Site Status

Divisione di Ematologia Osp. Businco

Cagliari, , Italy

Site Status

Onco-Ematologia I.R.C.C.

Candiolo (TO), , Italy

Site Status

Ematologia 1 Ospedale S. Martino

Genova, , Italy

Site Status

Divisione di Ematologia Ospedale Niguarda

Milan, , Italy

Site Status

UO Ematologia II Facoltà di Medicina e Chirurgia Università Federico II

Napoli, , Italy

Site Status

Divisione di Ematologia Università Avogadro

Novara, , Italy

Site Status

UO Ematologia Università - Policlinico San Matteo

Pavia, , Italy

Site Status

Dipartimento di biotecnologie cellulari ed ematologia Ospedale Umberto I - La Sapienza

Roma, , Italy

Site Status

Oncoematologia - Univ. Perugia Sede Terni,

Terni, , Italy

Site Status

S.C.Ematologia 1 AOU San Giovanni Battista

Torino, , Italy

Site Status

SC Ematologia 2 ASO San Giovanni Battista

Torino, , Italy

Site Status

UO Ematologia Osp. Cardinale Panico

Tricase (LE), , Italy

Site Status

Countries

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Italy

References

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Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, Spina M, Pavone V, Ladetto M, Liberati AM, Molinari AL, Zinzani P, Salvi F, Fattori PP, Zaccaria A, Dreyling M, Botto B, Castellino A, Congiu A, Gaudiano M, Zanni M, Ciccone G, Gaidano G, Rossi G; Fondazione Italiana Linfomi. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):730-7. doi: 10.1016/S1470-2045(14)70191-3. Epub 2014 May 13.

Reference Type DERIVED
PMID: 24831981 (View on PubMed)

Vose JM, Habermann TM, Czuczman MS, Zinzani PL, Reeder CB, Tuscano JM, Lossos IS, Li J, Pietronigro D, Witzig TE. Single-agent lenalidomide is active in patients with relapsed or refractory aggressive non-Hodgkin lymphoma who received prior stem cell transplantation. Br J Haematol. 2013 Sep;162(5):639-47. doi: 10.1111/bjh.12449. Epub 2013 Jul 9.

Reference Type DERIVED
PMID: 23834234 (View on PubMed)

Chiappella A, Tucci A, Castellino A, Pavone V, Baldi I, Carella AM, Orsucci L, Zanni M, Salvi F, Liberati AM, Gaidano G, Bottelli C, Rossini B, Perticone S, De Masi P, Ladetto M, Ciccone G, Palumbo A, Rossi G, Vitolo U; Fondazione Italiana Linfomi. Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi. Haematologica. 2013 Nov;98(11):1732-8. doi: 10.3324/haematol.2013.085134. Epub 2013 Jun 28.

Reference Type DERIVED
PMID: 23812930 (View on PubMed)

Other Identifiers

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IIL_REAL07

Identifier Type: -

Identifier Source: org_study_id