Follicular LymphomaPhase 3ILyADNCT03078855
A Study to Evaluate the Effect of Vitamin D on PFS in Indolent Non-Hodgkin's Lymphoma
A Phase 3 study testing Vitamin D and Rituximab in people with Follicular Lymphoma and Small Lymphocytic Lymphoma, run by Jonathan Friedberg at 7 sites in United States.
Trial summary
Despite strong evidence suggesting that vitamin D deficiency is associated with undesirable outcomes in patients with numerous cancers, there has never been a thorough study of vitamin D treatment in subjects undergoing treatment for cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma
- What is being tested?
- Vitamin D and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 211 participants
- Where
- 7 sitesUnited States
- Study dates
- 7 Sep 2017to 2 Jul 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Each of the following criteria must be met in order for a patient to be considered eligible for registration:
- Biopsy proven (with hematopathology review at one of the participating sites to confirm correct histology in accordance with World Health Organization) indolent lymphoma to include the following diagnoses:
- Grade 1, 2, or 3a follicular lymphoma
- Small lymphocytic lymphoma (CLL excluded)
- Marginal zone lymphoma (nodal or splenic)
- Mucosal-associated lymphoid tissue
Show all 18Show fewer
- Measurable disease defined by Lugano criteria
- No prior anti-lymphoma systemic therapy; prior radiation therapy allowed
- Age 18 or over
- Ann Arbor stages II, III or IV
- Patients with follicular lymphoma must have PET FDG-avid lymphoma and fulfill Low tumor burden by Groupe D'Etude des Lymphomes Folliculaires (GELF) criteria:
- No mass > 7 cm
- < 3 distinct masses of greater than 3 cm
- No B symptoms
- No splenomegaly > 16 cm by computed tomography (CT) scan
- No risk of vital organ compression
- No leukemic phase > 5000/µl circulating lymphocytes (except for in patients with splenic marginal zone diagnosis)
- No cytopenias (platelets < 100,000/µl, hemoglobin < 10 g/dl, or absolute neutrophil count < 1500/µl)
Who cannot join
- The following criteria will prevent inclusion of an inappropriate subject into the trial:
- Osteoporosis requiring prescription treatment
- Known symptomatic primary hyperparathyroidism
- Hypercalcemia defined as above the institutional normal range (corrected for albumin when albumin levels are below normal)
- History of calcium-related kidney stones
- Creatinine > 1.5X above upper limit of normal
- Women who are known to be pregnant or who plan to become pregnant while on rituximab treatment
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Emory University, Winship Cancer Institute
Atlanta, Georgia, 30322
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
University of Miami
Miami, Florida, 33136
Weill Cornell Medical College
New York, New York, 10021
James P. Wilmot Cancer Institute at University of Rochester Medical Center
Rochester, New York, 14642
Washington University
St Louis, Missouri, 63130
About this study
Official title: ILyAD (Indolent Lymphoma And Vitamin D) A Phase III Double Blind, Randomized Trial to Evaluate the Effect of Vitamin D on Progression-free Survival in Patients With Low Tumor-burden Indolent Non-Hodgkin Lymphoma Treated With Rituximab
Despite strong evidence suggesting that vitamin D deficiency is associated with undesirable outcomes in patients with numerous cancers, there has never been a thorough study of vitamin D treatment in subjects undergoing treatment for cancer. The purpose of this study is to evaluate whether modification of vitamin D levels in the blood, through supplementation, can improve outcomes.
- Conditions
- Follicular Lymphoma, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma, Mucosal-Associated Lymphoid Tissue Lymphoma
- Medical subject headings
- Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin DDietary supplement
Also called Cholecalciferol
vitamin D3 2,000 IU daily
RituximabBiological
Also called Rituxan
Administered weekly x 4
PlaceboOther
methylcellulose
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D plus rituximab | Experimental | Rituximab was administered weekly x 4 (intravenous 375 mg/m^2 or subcutaneous equivalent) per institutional standards and vitamin D3, 2000 IU orally once daily. Participants took vitamin D3 until lack of response at week 13, disease progression, or initiation of a new treatment. Receives: Dietary Supplement: Vitamin D; Biological: Rituximab |
| Placebo plus rituximab | Placebo comparator | Rituximab was administered weekly x 4 (intravenous 375 mg/m^2 or subcutaneous equivalent) per institutional standards and placebo orally once daily. Participants took placebo until lack of response at week 13, disease progression, or initiation of a new treatment. Receives: Biological: Rituximab; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival
Event free survival (EFS) was defined as the time from randomization to lack of response at week 13, initiation of a new treatment, disease progression defined by Lugano criteria, or death, right-censored by time of last follow-up. Per Lugano criteria, progression is defined as a new FDG-avid lesion or an increase in intensity from baseline, an increase by >= 50% in lesion diameters, a new lymph node > 1.5 cm in any axis or a new extranodal site > 1.0 cm.
Measured: 3 years
Secondary outcomes (2)
All-Cause Mortality
Number of participants who died from any cause between day 1 of treatment and the time of last follow-up.
Measured: Participants were followed for survival beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months.
Number of Participants With Treatment Response at 13 Weeks
Participants had imaging performed at week 13 to assess response to treatment. A response was defined as partial (PR) or complete response (CR) according to Lugano criteria. Per Lugano criteria for target lesions: PR includes reduced metabolic uptake or a ≥ 50% decrease in the sum of the products of the diameters compared to baseline. CR includes metabolic score of 1, 2 or 3 (out of 5) with or without residual mass or regression of target lesions to ≤ 1.5 cm in the longest dimension.
Measured: 13 Weeks from the start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2017
- Study start7 Sep 2017
- Primary completion21 Jul 2023
- Study completion2 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Follicular LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 211 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonathan Friedberg
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Jonathan Friedberg, University of Rochester
- Investigators
- Jonathan W. Friedberg, MD, Principal investigator, James P. Wilmot Cancer Institute at University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03078855
- Sponsor's protocol ID
- 66593
- Other IDs
- R01CA214890
- Acronym
- ILyAD
- Status last verified
- Aug 2024
- First submitted
- 8 Mar 2017
- Last updated
- 4 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data will be made available to researchers upon reasonable request.
Publications
Friedberg JW, Brady MT, Strawderman M, Kahl BS, Lossos IS, Cohen JB, Reagan PM, Casulo C, Averill BL, Baran A, Sutamtewagul G, Barr PM, Leonard JP, Ashton JM, Strang JG, Vega F, Peterson DR, Nastoupil LJ. Vitamin D in patients with low tumor-burden indolent non-Hodgkin lymphoma treated with rituximab therapy (ILyAD): a randomized, phase 3 clinical trial. EClinicalMedicine. 2024 Nov 27;78:102959. doi: 10.1016/j.eclinm.2024.102959. eCollection 2024 Dec.
PubMed 39677358
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ILyAD (Indolent Lymphoma And Vitamin D) A Phase III Double Blind, Randomized Trial to Evaluate the Effect of Vitamin D on Progression-free Survival in Patients With Low Tumor-burden Indolent Non-Hodgkin Lymphoma Treated With Rituximab
- ClinicalTrials.gov ID
- NCT03078855
- Acronym / sponsor ID
- ILyAD / 66593
- Conditions
- Follicular Lymphoma, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma, Mucosal-Associated Lymphoid Tissue Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 211 participants (actual)
- Lead sponsor
- Jonathan FriedbergUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- 7 Sep 2017 (actual)
- Primary completion
- 21 Jul 2023 (actual)
- Study completion
- 2 Jul 2024 (actual)
- First posted
- 13 Mar 2017 (actual)
- Results
- Posted 4 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite strong evidence suggesting that vitamin D deficiency is associated with undesirable outcomes in patients with numerous cancers, there has never been a thorough study of vitamin D treatment in subjects undergoing treatment for cancer. The purpose of this study is to evaluate whether modification of vitamin D levels in the blood, through supplementation, can improve outcomes.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin D plus rituximab | Experimental | Dietary Supplement: Vitamin D, Biological: RituximabRituximab was administered weekly x 4 (intravenous 375 mg/m^2 or subcutaneous equivalent) per institutional standards and vitamin D3, 2000 IU orally once daily. Participants took vitamin D3 until lack of response at week 13, disease progression, or initiation of a new treatment. |
| Placebo plus rituximab | Placebo comparator | Biological: Rituximab, Other: PlaceboRituximab was administered weekly x 4 (intravenous 375 mg/m^2 or subcutaneous equivalent) per institutional standards and placebo orally once daily. Participants took placebo until lack of response at week 13, disease progression, or initiation of a new treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Each of the following criteria must be met in order for a patient to be considered eligible for registration:
- Biopsy proven (with hematopathology review at one of the participating sites to confirm correct histology in accordance with World Health Organization) indolent lymphoma to include the following diagnoses:
- Measurable disease defined by Lugano criteria
- No prior anti-lymphoma systemic therapy; prior radiation therapy allowed
- Age 18 or over
Key exclusion criteria (7 listed)
- Osteoporosis requiring prescription treatment
- Known symptomatic primary hyperparathyroidism
- Hypercalcemia defined as above the institutional normal range (corrected for albumin when albumin levels are below normal)
- History of calcium-related kidney stones
- Creatinine > 1.5X above upper limit of normal
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin DAlso: Cholecalciferolvitamin D3 2,000 IU daily | Dietary supplement | Vitamin D plus rituximab |
| RituximabAlso: RituxanAdministered weekly x 4 | Biological | Placebo plus rituximab, Vitamin D plus rituximab |
| Placebomethylcellulose | Other | Placebo plus rituximab |
Primary outcome
Event Free Survival
Time frame: 3 years
Event free survival (EFS) was defined as the time from randomization to lack of response at week 13, initiation of a new treatment, disease progression defined by Lugano criteria, or death, right-censored by time of last follow-up. Per Lugano criteria, progression is defined as a new FDG-avid lesion or an increase in intensity from baseline, an increase by >= 50% in lesion diameters, a new lymph node > 1.5 cm in any axis or a new extranodal site > 1.0 cm.
2 secondary outcomes
All-Cause Mortality
Time frame: Participants were followed for survival beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months.
Number of Participants With Treatment Response at 13 Weeks
Time frame: 13 Weeks from the start of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39677358Friedberg JW, Brady MT, Strawderman M, Kahl BS, Lossos IS, Cohen JB, Reagan PM, Casulo C, Averill BL, Baran A, Sutamtewagul G, Barr PM, Leonard JP, Ashton JM, Strang JG, Vega F, Peterson DR, Nastoupil LJ. Vitamin D in patients with low tumor-burden indolent non-Hodgkin lymphoma treated with rituximab therapy (ILyAD): a randomized, phase 3 clinical trial. EClinicalMedicine. 2024 Nov 27;78:102959. doi: 10.1016/j.eclinm.2024.102959. eCollection 2024 Dec.
- Individual participant dataSharing planned: Yes. De-identified data will be made available to researchers upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan W. Friedberg, MD principal investigator
James P. Wilmot Cancer Institute at University of Rochester
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitamin D and Rituximab in people with Follicular Lymphoma and Small Lymphocytic Lymphoma, run by Jonathan Friedberg at 7 sites 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 18 inclusion and 7 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 4 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Event Free Survival (time frame: 3 years). 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 NCT03078855, which also lists 1 linked publication.
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 4 Sep 2024.