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

NCT02728531 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201603149
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Stem cell mobilization success rate

  -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.

  Completion of stem cell mobilization (approximately 25 weeks)

Secondary Outcomes (5)

• Overall response rate

  Completion of treatment (approximately 24 weeks)

• Pre-transplant complete response rate (CRR)

  Completion of treatment (approximately 24 weeks)

• Progression-free survival (PFS)

  5 years

• Overall survival (OS)

  5 years

• Safety and tolerability of bendamustine and rituximab alternating with cytarabine and rituximab as measured by grades 3 or higher toxicities

  30 days following completion of treatment (approximately 29 weeks)

Study Arms (1)

Bendamustine, Rituximab, Cytarabine

EXPERIMENTAL

* 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; Drug: Rituximab; Drug: Cytarabine; Drug: Pegfilgrastim; Procedure: Leukapheresis; Drug: Filgrastim; Procedure: Autologous stem cell transplant

Interventions

Bendamustine DRUG

Also known as: Bendamustine Hydrochloride, Treanda

Bendamustine, Rituximab, Cytarabine

Rituximab DRUG

Also known as: Rituxan

Bendamustine, Rituximab, Cytarabine

Cytarabine DRUG

Also known as: Cytosar-U, Tarabine PFS

Bendamustine, Rituximab, Cytarabine

Pegfilgrastim DRUG

Also known as: Neulasta, G-CSF

Bendamustine, Rituximab, Cytarabine

Leukapheresis PROCEDURE

Bendamustine, Rituximab, Cytarabine

Filgrastim DRUG

Also known as: Neupogen

Bendamustine, Rituximab, Cytarabine

Autologous stem cell transplant PROCEDURE

Bendamustine, Rituximab, Cytarabine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Merryman RW, Edwin N, Redd R, Bsat J, Chase M, LaCasce A, Freedman A, Jacobson C, Fisher D, Ng S, Crombie J, Kim A, Odejide O, Davids MS, Brown JR, Jacene H, Cashen A, Bartlett NL, Mehta-Shah N, Ghobadi A, Kahl B, Joyce R, Armand P, Jacobsen E. Rituximab/bendamustine and rituximab/cytarabine induction therapy for transplant-eligible mantle cell lymphoma. Blood Adv. 2020 Mar 10;4(5):858-867. doi: 10.1182/bloodadvances.2019001355.

  PMID: 32126141 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Bendamustine Hydrochloride; Rituximab; Cytarabine; pegfilgrastim; Granulocyte Colony-Stimulating Factor; Leukapheresis; Filgrastim

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Brad S Kahl, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: April 5, 2016
• Study Start: April 18, 2016
• Primary Completion: January 16, 2019
• Study Completion: August 16, 2023
• Last Updated: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)