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Large B-Cell Diffuse LymphomaPhase 1NCT03450343

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

A Phase 1 study testing Oral azacitidine and R-ICE in people with Large B-Cell Diffuse Lymphoma, run by Medical University of South Carolina at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Large B-Cell Diffuse Lymphoma
What is being tested?
Oral azacitidine and R-ICE
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
4 Apr 2019to 30 Jan 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • ALT ≤ 2.5 x ULN
  • Hematologic: Unless directly attributable to lymphoma within the bone marrow
  • Platelet count ≥ 75,000 cells/mm3
  • ANC ≥ 750 cells/mm3
  • HGB ≥ 8.0 cells/mm3
  • Renal
  • Serum creatinine ≤ 2.5 x ULN
  • Coagulation parameters:
  • PT ≤ 15 seconds
  • INR ≤ 1.5
  • PTT/aPTT < 40 seconds
  • Must have received at least one prior anti-CD20 containing multi-agent chemotherapy regimen (i.e. R-CHOP, R-EPOCH). Bendamustine and rituximab can be the prior regimen if used for follicular lymphoma or marginal zone lymphoma and subsequently transformed to DLBCL.
  • WOCBP should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with CC-486. All men and women of childbearing potential must use acceptable methods of birth control throughout the study as described below:
  • WOCBP: Recommendation is for two effective contraceptive methods during the study. Adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation.
  • Men with female partners who are of childbearing potential: Recommendation is for male and partner to use at least two effective contraceptive methods, as described above, during the study. Must agree to refrain from semen or sperm donation while taking CC-486 and for at least 90 days after last dose.

Who cannot join

  • 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
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  • 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
  • Myocardial infarction within the last 6 months
  • Active viral infection of hepatitis type B or C. Patients who are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or Hepatitis C antibody must have negative PCR prior to enrollment.
  • Seropositive for HIV
  • Known or suspected hypersensitivity to azacitidine or mannitol
  • Patients with advanced malignant hepatic tumors
  • Any condition causing an inability to swallow pills
  • Receipt of live vaccine within 28 days prior to registration.
  • Anti-cancer therapy within 21 days prior to registration. Prior radiation therapy within 14 days prior to registration.
  • Any other illness that in the opinion of the investigator, would exclude the patient from participating in this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

Other trials in United States

About this study

Official title: Oral Azacitidine (CC-486) Plus Salvage Chemotherapy in Relapsed/Refractory Diffuse Large B Cell Lymphoma

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.

Being tested
Oral azacitidine, R-ICE
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral azacitidineDrug

    Also called CC-486

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

  • R-ICEDrug

    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.

Study groups in NCT03450343
Study groupRoleWhat they receive
Oral azacitidine + R-ICEExperimentalPatients 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.
Receives: Drug: Oral azacitidine; Drug: R-ICE

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 126 days

Secondary outcomes (3)

  1. Response rate

    Overall response rate is the rate of complete response plus partial response. It will be assessed by the IWG 2014 response criteria for NHL and the Deuville Criteria for scan interpretation.

    Measured: While on study, between day 56 and day 70

  2. progression free survival

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

  3. Adequate peripheral stem cell collection

    This will be assessed by the number of stem cells collection prior to ASCT. Adequate collection is considered to be at least 2,000,000 CD34+ stem cells per kilogram.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2018
  2. Study start4 Apr 2019
  3. Primary completion31 Aug 2023
  4. Study completion30 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03450343
Sponsor's protocol ID
102732
Other IDs
OA-CL-DLBCL-PI-13065
Status last verified
Sep 2024
First submitted
26 Jan 2018
Last updated
28 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Oral azacitidine and R-ICE in people with Large B-Cell Diffuse Lymphoma, run by Medical University of South Carolina at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Presence or absence of a dose limiting toxicity in the combination of oral azacitidine and R-ICE (time frame: 126 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03450343.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2024.

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