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Bendamustine and Rituximab Alternating With Cytarabine and Rituximab for Untreated Mantle Cell Lymphoma

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02728531
Recruitment Status : Active, not recruiting
First Posted : April 5, 2016
Last Update Posted : May 19, 2020
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
Given the established role of high dose cytarabine (HiDAC) combined with rituximab, along with recent data showing the encouraging efficacy of bendamustine, the investigators seek to integrate the synergistic effects of these medicines in alternating cycles as induction therapy prior to autologous stem cell transplant (ASCT). Based on prior experience with bendamustine and rituximab (BR) based induction therapy, the investigators seek to evaluate the efficacy and safety of stem cell mobilization in this pilot study

Condition or disease Intervention/treatment Phase
Mantle Cell Lymphoma Drug: Bendamustine Drug: Rituximab Drug: Cytarabine Drug: Pegfilgrastim Procedure: Leukapheresis Drug: Filgrastim Procedure: Autologous stem cell transplant Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Bendamustine and Rituximab Alternating With Cytarabine and Rituximab for Untreated Mantle Cell Lymphoma
Actual Study Start Date : April 18, 2016
Actual Primary Completion Date : January 16, 2019
Estimated Study Completion Date : September 30, 2023


Arm Intervention/treatment
Experimental: Bendamustine, Rituximab, Cytarabine
  • Bendamustine on Days 1 and 2 of Cycles 1, 3, and 5.
  • In Cycle 1, rituximab on Day 1 or 2 at the investigator's discretion. Given on Day 1 of Cycles 2 through 6.
  • On Days 1 and 2 of Cycles 2, 4, and 6, cytarabine will be administered every 12 hours for a total of 4 doses.
  • Growth factor will be administered subcutaneously within 72 hours of completion of each even-numbered cycles of chemotherapy.
  • Leukapheresis will begin when the total WBC ≥ 5000/ μL and continue daily until collection of ≥ 2x106 CD34+ cells/kg (with a maximum of 5 courses of apheresis).
  • Standard of care peripheral blood autologous stem cell harvest will proceed per institutional guidelines and begin during Cycle 6 following rituximab and cytarabine therapy, when the total WBC ≥ 5000/ μL. Collection will continue on a daily basis until collection of ≥ 2x106 CD34+ cells/kg.
Drug: Bendamustine
Other Names:
  • Bendamustine Hydrochloride
  • Treanda

Drug: Rituximab
Other Name: Rituxan

Drug: Cytarabine
Other Names:
  • Cytosar-U
  • Tarabine PFS

Drug: Pegfilgrastim
Other Names:
  • Neulasta
  • G-CSF

Procedure: Leukapheresis
Drug: Filgrastim
Other Name: Neupogen

Procedure: Autologous stem cell transplant



Primary Outcome Measures :
  1. Stem cell mobilization success rate [ Time Frame: Completion of stem cell mobilization (approximately 25 weeks) ]
    -Stem cell mobilization success is defined as a yield of ≥ 2 x 106 CD34+ stem cells/kg with a maximum of 5 courses of apheresis.


Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: Completion of treatment (approximately 24 weeks) ]
    -Response to treatment is guided based upon the Recommendations for Initial Evaluation, Staging and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification.

  2. Pre-transplant complete response rate (CRR) [ Time Frame: Completion of treatment (approximately 24 weeks) ]

    CRR=

    • Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
    • London Deauville score of 1 and 2 in lymph nodes and extra lymphatic sites is considered to represent complete metabolic response. A London Deauville score 3 in the post treatment PET scan may be considered to represent complete metabolic response especially if it is not higher than the surrounding normal physiologic uptake.
    • No evidence of FDG avid disease in the bone marrow
    • No new lesions
    • If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy.

  3. Progression-free survival (PFS) [ Time Frame: 5 years ]
    -PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

  4. Overall survival (OS) [ Time Frame: 5 years ]
  5. Safety and tolerability of bendamustine and rituximab alternating with cytarabine and rituximab as measured by grades 3 or higher toxicities [ Time Frame: 30 days following completion of treatment (approximately 29 weeks) ]
    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed mantle cell lymphoma with documented expression of CD20 (or CD 19) and cyclin D1 (BCL1) by immunohistochemical stains and/or t (11; 14) by cytogenetics or FISH
  • Eighteen to 65 years of age, inclusive.
  • Presence of evaluable disease by PET imaging per the Lugano classification (Cheson 201418)
  • Eligible for autologous stem cell transplantation.
  • ECOG performance status ≤ 2
  • Normal bone marrow and organ function as defined below:

    • Absolute neutrophil count ≥ 1,000/mcl unless in the opinion of the treating physician, neutropenia is due to splenomegaly or bone marrow involvement
    • Platelets ≥ 100,000/mcl unless in the opinion of the treating physician, thrombocytopenia is due to splenomegaly or bone marrow involvement
    • Total bilirubin ≤ 2 x IULN and AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN except when, in the opinion of the treating physician, is due to direct involvement of lymphoma (e.g., hepatic infiltration or biliary obstruction due to lymphoma) or Gilbert's disease
    • Creatinine ≤ IULN OR creatinine clearance ≥ 40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
  • Negative HIV serology.

Exclusion Criteria:

  • Any previous chemotherapy or radiation for mantle cell lymphoma. Short course of steroids for symptom relief prior to presentation is permissible.
  • Symptomatic meningeal or parenchymal brain lymphoma.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab, cytarabine, bendamustine or other agents used in the study.
  • Severe concurrent illness, which would limit compliance with study requirements.
  • Subjects with serologic status reflecting active viral hepatitis B or C infection are not eligible. Subjects whoare hepatitis B core antibody positive but antigen negative will need negative polymerase chain reaction (PCR) prior to enrollment. Hepatitis B surface antigen positive or PCR positive patients will be excluded. Subjects who are hepatitis C antibody positive will need negative PCR prior to enrollment. Patients with positive hepatitis C will be excluded.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of study entry.

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 ClinicalTrials.gov identifier (NCT number): NCT02728531


Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Brad S Kahl, M.D. Washington University School of Medicine
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02728531    
Other Study ID Numbers: 201603149
First Posted: April 5, 2016    Key Record Dates
Last Update Posted: May 19, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cytarabine
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Antineoplastic Agents, Alkylating
Alkylating Agents