Clinical Trial to Determinate Dose, Security and Efficacy or Lenalidomide and Rituximab (LR)-ESHAP in Patients With Diffuse Large B-cell Lymphoma

• Status: Completed
• Trial end date: 2019-02-20
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of the Phase I of the study is to evaluate the safety and the maximum-tolerated dose (MTD) of the combination R-ESHAP with lenalidomide as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma The purpose of the Phase II of the study is to evaluate ORR of LR-ESHAP in patients with relapsed or refractory DLBCL candidates to HDT and ASCT

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
• Collaborators: Celgene Corporation; Dynamic Science S.L.; Thermo Fisher Scientific
• Treatments: Cisplatin; Cytarabine; Etoposide; Etoposide phosphate; Lenalidomide; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Rituximab; Thalidomide

Criteria

Inclusion Criteria:

1. The patient must, at the investigator's opinion, be able to meet all requirements of the clinical trial.

2. Patients must give voluntarily informed consent before performing any test test that is not part of routine care of patients.

3. Age between 18 and 70 years.

4. Candidate for treatment with high-dose QT and HSCT .

5. Diffuse large B-cell lymphoma (LDCGB) histological diagnosis according to the WHO classification ( see Annex 8).

6. Refractory lymphoma or relapsed after 1st line treatment consisting of rituximab combined with a regimen of chemotherapy (CT scan ) including anthracyclines. :

Relapse is defined as recurrence of lymphoma after obtaining complete response (RC) with 1st line treatment . In these cases, LDCGB histologic confirmation at the time of relapse is recommended

Refractory lymphoma be considered if it meets one of the following criteria :

partial response after at least 6 cycles of 1st line regimen . They may also include patients in partial response after 4 cycles if the researcher believes that the response is suboptimal, and patients with stage I- II if they have received 3 cycles of R- QT + affection field radiotherapy .

stable disease after at least 3 cycles of 1st line regimen . progression during treatment of 1st line , defined as response criteria for malignant lymphoma 2007 (see Annex 9)

7. CT scan evidence of at least two clearly demarcated lesions with a diameter of 1.5 cm, or 1 well-defined lesion with a diameter > 2 cm .

8. Evidence of positive lesions by PET, coincident with the anatomical areas affected by CT scan .

9. Eastern cooperative oncology group performance status (ECOG) less than or equal to 2.

10. Resolution of toxicities caused by the 1st line regimen to less than or equal to grade 1.

11. Women of childbearing age ( see Appendix 12) must: Obtain a negative pregnancy test before starting medically supervised therapy study. Must accept continuing pregnancy tests conducted during the course of the study and after the end of study therapy . This applies even if the patient practices complete and continued abstinence .

They must either commit to continued abstinence or heterosexual sex (which should be reviewed monthly ) or agree to use and be capable of complying with effective contraception without interruption, 28 days before starting the study drug during the study therapy (including during periods of dose interruptions ) , and for 28 days after discontinuation of study therapy .

12 male patients ( see Appendix 12) must:

• Accept to use a latex condom during any sexual relations with women of childbearing potential , even if they have had a vasectomy , while participating in this study, during dose interruptions and after discontinuation of treatment .

• Accept refrain from donating sperm while participating in this study and for a time after cessation of treatment (see specific data ) . 13. All patients must: Understand that the study drug could potentially have a teratogenic risk . Agree to abstain from donating blood while they are taking the treatment and after discontinuation of study drug therapy .

Agree not to share study medication with anyone else. For advice on precautions against pregnancy and potential risks of fetal exposure

Exclusion Criteria:

1. Patients that previously received any antitumor agent for the treatment of LDCGB except : I ) rituximab in combination with regimen including anthracyclines II ) radiotherapy as part of first-line treatment .

2 Previously received any of the following treatments in the 28 days prior to the test regime : I ) antitumor chemotherapeutic agents ; II ) radiotherapy , unless limited to a maximum dose of < or =10 Gy to control severe life-threatening symptoms ; III ) glucocorticoid except equivalent doses < or = 1 mg / kg of prednisolone / day with duration < or = 7 days; iv ) any therapeutic agent under investigation.

3. Known involvement of the central nervous system (CNS) by lymphoma. 4. Presence of abnormal or clinically significant cardiac disease, such as acute myocardial infarction or unstable angina within 6 months prior to initiation of treatment with LR- ESHAP , grade III or IV heart failure, uncontrolled hypertension or history of poor compliance with antihypertensive treatment , uncontrolled treated arrhythmias, except , with the exception of extra systoles or minor conduction abnormalities.

5. Any other serious or uncontrolled medical condition , such as diabetes, uncontrolled active infection, significant cerebrovascular disease, poorly controlled psychiatric disease, etc. .

6. Known or suspected hypersensitivity to any of the agents of the treatment under evaluation.

7. Presence of any limitations that compromise the patient's ability to comply with treatment .

8. Positive serology for HIV or Hepatitis B Virus (HBV) surface antigen (HBsAg ) . If negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test will be performed and if positive the subject will be excluded. Note: If HBcAb positive and HBsAb positive, which is indicative of a past infection, the subject can be included 9. Active Hepatitis C (RNA positive serum) . If RNA positive result would exclude the patient from the trial in cases of patients with positive serology for Hepatitis C Virus (HCV). If the load ( RNA ) were HCV negative patients could be included in the study.

10. Prior history of malignancy other than to LDCGB (except basal or squamous cell skin and in situ carcinoma of the cervix or breast ) unless the patient free of disease beyond 5 years are.

11 Changes in laboratory values ??that might involve unacceptable risks or compromise compliance with the protocol , including: platelets < 50 x 109 / L or neutrophils <1 x 109 / L , unless attributed to infiltration by lymphoma bone marrow (MO) .

or creatinine > 1.5 times the normal upper limit . or Total bilirubin > 2 times the upper limit of normal or alanine aminotransferase (ALT) > 2.5 times the normal upper limit or alkaline phosphatase > 2.5 times the normal upper limit , unless it is attributed to hepatic infiltration by lymphoma.

12. Pregnant or breast-feeding. 13. Females of childbearing potential who do not agree to undergo pregnancy tests or repeated use effective birth control while included in the clinical trial.

14. Males patients (whose sexual partners are women of childbearing potential ) that not accept use effective birth control methods while included in the clinical trial.