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

Follicular Lymphoma Clinical Trial

— REAL07  

Official title:

Prospective Multicenter Dose Finding Phase II Pilot Trial to Evaluate Efficacy and Safety of Treatment With Lenalidomide Plus R-CHOP21 (LR-CHOP21) for Elderly Patients With Untreated Diffuse Large B Cell Lymphoma (DLBCL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00907348
• Other study ID #: IIL_REAL07
• Status: Active, not recruiting
• Phase: Phase 2
• First received: May 21, 2009
• Last updated: October 12, 2011
• Start date: October 2007
• Est. completion date: January 2012

Study information

• Verified date: October 2011
• Source: Fondazione Italiana Linfomi ONLUS
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 49
• Est. completion date: January 2012
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 80 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Italy	Divisione di Ematologia Osp. SS. Antonio e Biagio	Alessandria
Italy	Divisione di Oncologia Medica A Centro di Riferimento Oncologico	Aviano
Italy	Cattedra di Ematologia Università Policlinico	Bari
Italy	IRCCS Istituto Tumori Giovanni Paolo II	Bari
Italy	Istituto di Ematologia "Seragnoli" Polic.S.Orsola-Malpighi	Bologna
Italy	Divisione di Ematologia Spedali Civili	Brescia
Italy	Divisione di Ematologia Osp. Businco	Cagliari
Italy	Onco-Ematologia I.R.C.C.	Candiolo (TO)
Italy	Ematologia 1 Ospedale S. Martino	Genova
Italy	Divisione di Ematologia Ospedale Niguarda	Milano
Italy	UO Ematologia II Facoltà di Medicina e Chirurgia Università Federico II	Napoli
Italy	Divisione di Ematologia Università Avogadro	Novara
Italy	UO Ematologia Università - Policlinico San Matteo	Pavia
Italy	Dipartimento di biotecnologie cellulari ed ematologia Ospedale Umberto I - La Sapienza	Roma
Italy	Oncoematologia - Univ. Perugia Sede Terni,	Terni
Italy	S.C.Ematologia 1 AOU San Giovanni Battista	Torino
Italy	SC Ematologia 2 ASO San Giovanni Battista	Torino
Italy	UO Ematologia Osp. Cardinale Panico	Tricase (LE)

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi ONLUS	Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of adverse events according with Common Terminology Criteria for Adverse events (CTCAE)		2 years	Yes
Secondary	Overall Response Rate (ORR)		4 years	Yes