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Rituximab, Bendamustine and Cytarabine Followed by Venetoclax in High Risk Elderly Patients With MCL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03567876
Recruitment Status : Recruiting
First Posted : June 26, 2018
Last Update Posted : February 6, 2020
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS

Brief Summary:
Prospective, multicenter, phase II trial designed to evaluate whether the addition of Venetoclax after rituximab, bendamustine and cytarabine (R-BAC) to high risk patients with mantle cell lymphoma improves the results of the standard R-BAC, in terms of Progression Free Survival.

Condition or disease Intervention/treatment Phase
Lymphoma, Mantle-Cell Drug: Venetoclax Phase 2

Detailed Description:

The aim of the study is to improve long term results of R-BAC, consolidating patients with high-risk (HR) features (defined as: elevated Ki67 and/or blastoid cytology and/or TP53 mutation after central pathology review) with Venetoclax (ABT-199), which has demonstrated relevant single agent activity in relapsed/refractory MCL in a Phase 1-2 trial.

The updated Progression Free Survival curves of the R-BAC500 trial has shown that the expected 2-years PFS for patients with HR disease is 40% (H0), as compared to low-risk patients (LR) that have a 2-years PFS of 100%. The addition of Venetoclax to HR patients after R-BAC is expected to improve results and efficacy of this regimen in this "difficult -to- treat" population, that represents approximately 40-45 % of newly diagnosed elderly patients with MCL. It appears reasonable to treat with the experimental drug also LR patients that do not respond appropriately (less than CR) at the end of R-BAC. Since the number of such LR patients is hardly predictable based on the present experience with R-BAC500 trial, the analysis of this sub-cohort will be of exploratory nature, and thus assessed separately.

The study objective is to evaluate whether the addition of venetoclax after R-BAC to HR patients improves the results of the standard R-BAC, in terms of Progression Free Survival .

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Rituximab, Bendamustine and Cytarabine Followed by Venetoclax (V-RBAC) in High-risk Elderly Patients With Mantle Cell Lymphoma (MCL)
Actual Study Start Date : September 3, 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Venetoclax

Arm Intervention/treatment
Experimental: V-RBAC (RBAC followed by Venetoclax)

Induction phase: RBAC --> up to 6 cycles for low risk (LR) patients and up to 4 cycles for high risk (HR) patients.

Patients proceeding to Venetoclax treatment will receive consolidation with single agent Venetoclax 800 mg/die x 4 28d cycles (with initial ramp-up dose) of each consolidation cycle. Consolidation will be followed by maintenance with single agent Venetoclax 400 mg/die (V maint ) for a total of 2 years (4 months consolidation+20 months maintenance).

Drug: Venetoclax
Consolidation and maintenance phases with Venetoclax (for a total of 2 years) after an induction phase R-BAC (up to 6 cycles for law risk patients and up to 4 cycles for high risk patients)
Other Name: Venclyxto (commercial name)

Primary Outcome Measures :
  1. Progression-free survival of the High Risk patients [ Time Frame: 24 months ]
    2-years progression-free survival (PFS) of the HR patients from date of enrollment

Secondary Outcome Measures :
  1. Molecular response [ Time Frame: 10 months and 30 months ]
    The proportion of molecular response (analyzed in the labs of the FIL- MRD Network)

  2. Progression-free survival of all patients and different subgroups [ Time Frame: 24 months ]
    The progression-free survival (PFS) of all enrolled patients, and of different subgroups (i.e TP53 mutated patients)

  3. Overall survival [ Time Frame: 54 months ]
    Overall survival

  4. Duration of responses [ Time Frame: 24 months ]
    Duration of responses

  5. Proportion of complete remission in High Risk and Law Risk patients [ Time Frame: 6 months and 10 months ]
    The proportion of complete remission (CR) before and after venetoclax in the HR group and/or in the LR not responding to R-BAC

  6. Completed expected treatment schedule [ Time Frame: 30 months ]
    The proportion of patients that complete the expected treatment schedule

  7. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 10 months and 30 months ]
    The proportion of patients with adverse events as assessed by CTCAE 4.03 during venetoclax administration as consolidation or maintenance after R-BAC

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Previously untreated patients with MCL aged ≥65 years if they are FIT according to the geriatric CGA assessment.
  2. age ≤64 years not eliglible to high-dose chemotherapy plus transplantation at physician's judgement (details for non eligibility to be recorded by means of the CIRS, Cumulative Illness rating Scale).
  3. Measurable nodal or extranodal disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions.
  4. ECOG performance status ≤2.
  5. Positivity for cyclin D1 and/or SOX11 [the latter being mandatory in cases lacking cyclin D1- or t(11;14)-negative].
  6. Adequate renal function (Creatinine clearance >50 mL/min), with preserved diuresis.
  7. Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <2.5 x upper limit of normal (ULN) value, total bilirubin <1.5 x ULN, unless directly attributable to the patient's tumor or to congenital causes.
  8. Hepatitis B core antibody (HBcAb) positive/HBsAg negative/HBV-DNA negative patients may be enrolled if correct antiviral prophylaxis is administered at least 2 weeks before initiating protocol treatment.
  9. Written informed consent.

Exclusion Criteria:

  1. Human immunodeficiency virus (HIV) positive.
  2. Previous treatment for lymphoma.
  3. Disease confined to the bone marrow/peripheral blood/spleen, without any other nodal or extranodal involvement.
  4. In-situ MCL.
  5. Medical conditions or organ injuries that could interfere with administration of therapy.
  6. Active bacterial, viral, or fungal infection requiring systemic therapy.
  7. Seizure disorders requiring anticonvulsant therapy.
  8. Severe chronic obstructive pulmonary disease with hypoxiemia.
  9. History of severe cardiac disease: New York Heart Association (NYHA) functional class III-IV, myocardial infarction within 6 months, ventricular tachyarrhythmias, dilatative cardiomyopathy, or unstable angina.
  10. Uncontrolled diabetes mellitus.
  11. Active secondary malignancy.
  12. Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins, to Bendamustine or mannitol.
  13. Major surgery within 4 weeks of study Day 1.
  14. HBsAg+
  15. HCVAb+ patients with active viral replication (HCV-RNA+ with AST>2 x normal limit)
  16. Any co-existing medical or psychological condition that would preclude participation in the study or compromise the patient's ability to give informed consent, or that may affect the interpretation of the results, or render the patient at high risk from treatment complications.
  17. CNS involvement
  18. Chronic treatment with strong or moderate CYP3A inhibitors (e.g. ketoconazole, ritonavir, clarithromycin, itraconazole, voriconazole)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03567876

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Contact: Claudia Peracchio 00390131033154
Contact: Antonella Ferranti 00390131033153

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Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
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Principal Investigator: Carlo Visco, MD AOU Integrata di Verona - U.O. Ematologia -Verona -Italy
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Responsible Party: Fondazione Italiana Linfomi ONLUS Identifier: NCT03567876    
Other Study ID Numbers: FIL_V-RBAC
First Posted: June 26, 2018    Key Record Dates
Last Update Posted: February 6, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fondazione Italiana Linfomi ONLUS:
Mantle cell lymphoma
Elderly patients
First line
Additional relevant MeSH terms:
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Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antineoplastic Agents