Oral Azacitidine Plus Salvage Chemotherapy in Relapsed/Refractory Diffuse Large B Cell Lymphoma

NCT03450343 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 102732OA-CL-DLBCL-PI-13065
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and tolerability of adding oral azacitidine to the chemotherapy combination R-ICE. This study will also look at whether or not disease outcomes improve with the combination.

Conditions

Large B-Cell Diffuse Lymphoma

Outcome Measures

Primary Outcomes (1)

• Presence or absence of a dose limiting toxicity in the combination of oral azacitidine and R-ICE

  A 3+3 dose-escalation design will be used to determine the recommended phase II dose.

  126 days

Secondary Outcomes (3)

• Response rate

  While on study, between day 56 and day 70

• progression free survival

  From start of treatment to time of documented progression or date of death, whichever occurs first, assessed up to 1 year.

• Adequate peripheral stem cell collection

  At the time of ASCT (10 weeks after start of study therapy)

Study Arms (1)

Oral azacitidine + R-ICE

EXPERIMENTAL

Patients will receive 7 days of oral azacitidine (CC-486) leading into cycle 1 day 1 of R-ICE chemotherapy. R-ICE chemotherapy may be administered as an inpatient or as an outpatient . Oral azacitidine will be administered on days 8-21 of cycles 1 and cycle 2. R-ICE will be administered per standard of care.

Drug: Oral azacitidine; Drug: R-ICE

Interventions

Oral azacitidine DRUG

Azacitidine can be taken with or without food at the same time every day.

Also known as: CC-486

Oral azacitidine + R-ICE

R-ICE DRUG

R-ICE is approved for the treatment of NHL before ASCT for relapsed or primary refractory diffuse large b-cell lymphoma. R-ICE consists of rituximab, etoposide, carboplatin and ifosfamide. R-ICE will be administered per institutional guidelines.

Oral azacitidine + R-ICE

Eligibility Criteria

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

You may qualify if:

• Histologic confirmation of relapsed/refractory disease of one of the following:
• DLBCL
• Transformed DLBCL (from follicular lymphoma or marginal zone lymphoma but not from CLL)
• Grade 3B follicular lymphoma
• B-Cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma
• Primary mediastinal B cell lymphoma
• Eligible for high dose chemotherapy and autologous stem cell transplant determined by treating physician
• Measurable disease on cross section imaging by PET and/or CT that is at least 1.5 cm in the longest diameter and measurable in two perpendicular dimensions as defined by IWG criteria. See Section 12.1.
• At least 18 years old
• Able to understand and voluntarily sign consent prior to any study related assessments or procedures are performed.
• Performance status of 0-2 on the ECOG scale (see Appendix A).
• Adequate organ function defined by the following
• Hepatic
• Serum bilirubin ≤ 1.5 X ULN unless attributed to Gilbert's syndrome or hemolysis.
• AST ≤ 2.5 x ULN

You may not qualify if:

• Women who are pregnant or breast-feeding. Lactating women must agree not to breast feed while taking CC-486 and for at least 90 days after the last dose. WOCBP will have a serum pregnancy test within 72 hours before starting study treatment on day -6. Pregnancy test must be negative in order to move forward with study treatment.
• More than three prior treatments for the large cell component of lymphoma (i.e. induction chemotherapy and salvage chemotherapy). Radiation therapy does not count as a line of therapy.
• Patients with history or active CNS lymphoma
• Previous history of autologous or allogeneic stem cell transplantation
• Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment)
• History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity
• History of stroke or intracranial hemorrhage within 6 months prior to registration.
• Prior history of malignancy other than DLBCL unless subject is free of disease for more than 2 years from signing consent. Exceptions include the following:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix or breast
• Previously treated localized prostate cancer with normal PSA levels
• Significant active cardiac disease defined as the following
• NYHA class III or IV CHF (Appendix B)
• Unstable angina

Sponsors & Collaborators

• Medical University of South Carolina: lead
• Celgene Corporation: collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Azacitidine; cc-486

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; 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)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Brian Hess, MD

  Medical University of South Carolina

  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: January 26, 2018
• First Posted: March 1, 2018
• Study Start: April 4, 2019
• Primary Completion: August 31, 2023
• Study Completion: January 30, 2024
• Last Updated: October 28, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)