LymphomaPhase 2NCT03919175
Umbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma
A Phase 2 study testing Umbralisib and Rituximab in people with Lymphoma and Follicular Lymphoma, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
This research is being done to assess Umbralisib and Rituximab as a first line therapy for Follicular Lymphoma or Marginal Zone Lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Follicular Lymphoma, Follicular Lymphoma, Grade 1
- What is being tested?
- Umbralisib and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Sep 2019to 5 May 2024
- Phase
- Phase 2
- 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
- Participants must have histologically confirmed follicular lymphoma grade 1-3A or marginal zone lymphoma by WHO criteria.
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter [LDi] to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥15 mm in LDi for nodal disease or >10 mm in LDi for extranodal lesions.
- Requires therapy based on: symptomatic disease, threatened end-organ dysfunction, compressive disease, cytopenias secondary to lymphoma, bulky disease (defined as any site ≥7 cm, or 3 or more sites ≥3cm), or steady progression.
- For patients with follicular lymphoma: No prior systemic therapy for follicular lymphoma. Prior radiation to a single site of disease is allowed if completed at least 2 weeks prior to initiation of protocol therapy and there are additional sites of measurable disease outside of the radiation field.
- For patients with marginal zone lymphoma: No prior systemic therapy for marginal zone lymphoma. Prior radiation or surgical resection is allowed if there are additional sites of measurable disease outside of the radiation field. Prior radiation must be completed at least 2 weeks prior to initiation of protocol therapy. Prior H. pylori eradication therapy is allowed.
- Age >18 years.
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- ECOG performance status ≤2
- Participants must have adequate organ function as defined below:
- total bilirubin <1.5 x institutional upper limit of normal (ULN) or <3 x ULN if considered due to Gilbert's syndrome
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- creatinine within normal institutional limits OR
- creatinine clearance ≥30 mL/min for participants with creatinine levels above institutional normal.
- Participants must have adequate marrow function as defined below (unless abnormalities are considered related to marrow involvement by lymphoma):
- absolute neutrophil count ≥1,000/mcL (500/mcL is acceptable if due to marrow involvement by lymphoma)
- platelets ≥70,000/mcL(30,000/mcL is acceptable if due to marrow involvement by lymphoma)
- Female participants who are not of child-bearing potential and female participants of child-bearing potential who have a negative serum pregnancy test within 3 days prior to initial trial treatment. Female participants of child-bearing potential and all male partners, and male participants must consent to use a medically acceptable method of contraception throughout the study period and for a minimum of 1 year after the last dose of rituximab and for a minimum of 4 months after the last dose of umbralisib.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Participants who require immediate cytoreduction per the treating investigator.
- For patients with H. pylori related gastric extranodal marginal zone lymphoma in the absence of t(11;18): Patient must have relapsed or refractory marginal zone lymphoma despite appropriate H. pylori eradication.
- For patients with hepatitis C virus related marginal zone lymphoma: Patient must have relapsed or refractory marginal zone lymphoma despite appropriate treatment of hepatitis C virus infection.
- Active systemic therapy for another malignancy within 2 years. Local/regional therapy with curative intent such as surgical resection or localized radiation is allowed if patient is deemed at low risk for recurrence by treating physician.
- Malignancy within 3 years of study enrollment except for adequately treated basal, squamous cell carcinoma or non-melanomatous skin cancer, carcinoma in situ of the cervix, superficial bladder cancer not treated with intravesical chemotherapy or BCG within 6 months, localized prostate cancer and PSA <1.0 mg/dL on 2 consecutive measurements at least 3 months apart with the most recent one being within 4 weeks of study entry.
- Corticosteroid therapy (prednisone >10 mg daily or equivalent) is not permitted within 7 days prior to study entry. Topical, or intra-articular or inhaled corticosteroids are permitted.
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- Prior allogeneic stem cell transplant.
- Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis)
- Malabsorption syndromes
- Irritable bowel syndrome with greater than 3 loose stools per day as a baseline.
- Known central nervous system involvement by lymphoma.
- Evidence of histological transformation to large cell lymphoma.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to umbralisib or rituximab.
- Evidence of ongoing systemic bacterial, fungal or viral infection, except localized fungal infections of skin or nails.
- Evidence of chronic active Hepatitis B (HBV, not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody) or chronic active Hepatitis C infection (HCV), active cytomegalovirus (CMV), or known history of HIV. If HBc antibody is positive, the patient must be evaluated for the presence of HBV DNA (by PCR). If HCV antibody is positive, the subject must be evaluated for the presence of HCV RNA by PCR. If the patient is CMV IgG or CMV IgM positive, the subject must be evaluated for the presence of CMV DNA by PCR. Patients with positive HBc antibody and negative HBV DNA via PCR are eligible, but prophylaxis with entecavir or lamivudine is recommended. Subjects who are CMV IgG or CMV IgM positive but who are CMV DNA negative by PCR are eligible, but antiviral prophylaxis should be considered per institutional protocol.
- Any severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study such as:
- Symptomatic, or history of documented congestive heart failure (New York Heart Association functional classification III-IV [see Appendix: NYHA Classifications])
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, CHF, or myocardial infarction within 6 months of enrollment.
- Concomitant use of medication known to cause QT prolongation or torsades de pointes should be used with caution and at investigator discretion.
- Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), symptomatic peripheral arterial disease, angioplasty, cardiac or vascular stenting within 6 months of enrollment.
- Psychiatric illness/social situations that would limit compliance with study requirements
- Known history of drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver.
- Pregnant women are excluded from this study because rituximab is an agent with known potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with rituximab or umbralisib, breastfeeding should be discontinued if the mother is treated with rituximab or umbralisib. These potential risks may also apply to other agents used in this study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Beth Israel Deaconness Medical Center
Boston, Massachusetts, 02215
About this study
Official title: A Phase 2 Study of Umbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma
This research is being done to assess Umbralisib and Rituximab as a first line therapy for Follicular Lymphoma or Marginal Zone Lymphoma.
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The U.S. Food and Drug Administration (FDA) has not approved Umbralisib as a treatment for any disease.
The FDA has approved Rituximab as a treatment option for this disease.
Umbralisib is an investigational drug which blocks a protein called PI3K. PI3K is a protein that plays a role in the way cells grow. In this type of cancer, PI3K is increased and more active than usual. This helps the cancer cells to grow and survive. Early clinical trials have shown that Umbralisib can kill cancer cells in some patients and cause their tumors to shrink.
- Conditions
- Lymphoma, Follicular Lymphoma, Follicular Lymphoma, Grade 1, Follicular Lymphoma Grade 2, Follicular Lymphoma Grade IIIa, Marginal Zone Lymphoma
- Being tested
- Umbralisib, Rituximab
- Keywords
- Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma
- Medical subject headings
- Lymphoma, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UmbralisibDrug
Also called TGR-1202
Umbralisib is an investigational drug which blocks a protein called PI3K. PI3K is a protein that plays a role in the way cells grow. In this type of cancer, PI3K is increased and more active than usual. This helps the cancer cells to grow and survive.
RituximabDrug
Also called MabThera
Rituximab works by targeting the CD20 antigen on normal and malignant B-cells. Then the body's natural immune defenses are recruited to attack and kill the marked B-cells
| Study group | Role | What they receive |
|---|---|---|
| Umbralisib+Rituximab | Experimental | * A treatment cycle is defined as 28 consecutive days.
* Umbralisib will be administered at 800 mg by mouth once daily on days 1-28 of cycles 1-24.
* Rituximab will be administered at 375 mg/m2 by intravenous infusion on Cycle 1 Day 1 and may be administered at 375 mg/m2 by intravenous infusion or at 1400 mg by subcutaneous injection on days 8, 15, 22 of cycle 1, day 1 of cycles 2 to 6, then every 8 weeks starting on day 1 of cycle 7 until completion of 24 cycles of umbralisib (i.e. every other cycle for 18 cycles or 9 doses, for a total of 15 doses of rituximab), or until progression or intolerance. Receives: Drug: Umbralisib; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response Rate
The frequency of patients who achieve a complete response per 2014 Lugano criteria.
Measured: 2 years
Secondary outcomes (4)
Overall Response Rate
The frequency of patients who achieve a complete or partial response per 2014 Lugano criteria
Measured: 2 years
Progression Free Survival
The median progression-free survival using Kaplan-Meier method with time of registration as time origin.
Measured: 2 years
Overall Survival
The median overall survival using Kaplan-Meier method with time of registration as time origin.
Measured: 2 Years
Number of Participants With Adverse Events
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2019
- Study start1 Sep 2019
- Primary completion5 May 2024
- Study completion5 May 2024
Why it stopped: Umbralisib development terminated; closed to accrual 8/29/2022
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.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- TG Therapeutics
- Responsible party
- Principal investigator, Jacob Soumerai, MD, Massachusetts General Hospital
- Investigators
- Jacob D. Soumerai, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03919175
- Sponsor's protocol ID
- 19-011
- Status last verified
- Feb 2026
- First submitted
- 15 Apr 2019
- Last updated
- 27 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Umbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma
- ClinicalTrials.gov ID
- NCT03919175
- Acronym / sponsor ID
- 19-011
- Conditions
- Lymphoma, Follicular Lymphoma, Follicular Lymphoma, Grade 1, Follicular Lymphoma Grade 2, Follicular Lymphoma Grade IIIa, Marginal Zone Lymphoma
- Keywords
- Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Umbralisib development terminated; closed to accrual 8/29/2022
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- TG Therapeutics
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 5 May 2024 (actual)
- Study completion
- 5 May 2024 (actual)
- First posted
- 18 Apr 2019 (actual)
- Results
- Posted 27 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research is being done to assess Umbralisib and Rituximab as a first line therapy for Follicular Lymphoma or Marginal Zone Lymphoma.
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The U.S. Food and Drug Administration (FDA) has not approved Umbralisib as a treatment for any disease.
The FDA has approved Rituximab as a treatment option for this disease.
Umbralisib is an investigational drug which blocks a protein called PI3K. PI3K is a protein that plays a role in the way cells grow. In this type of cancer, PI3K is increased and more active than usual. This helps the cancer cells to grow and survive. Early clinical trials have shown that Umbralisib can kill cancer cells in some patients and cause their tumors to shrink.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Umbralisib+Rituximab | Experimental | Drug: Umbralisib, Drug: Rituximab* A treatment cycle is defined as 28 consecutive days. * Umbralisib will be administered at 800 mg by mouth once daily on days 1-28 of cycles 1-24. * Rituximab will be administered at 375 mg/m2 by intravenous infusion on Cycle 1 Day 1 and may be administered at 375 mg/m2 by intravenous infusion or at 1400 mg by subcutaneous injection on days 8, 15, 22 of cycle 1, day 1 of cycles 2 to 6, then every 8 weeks starting on day 1 of cycle 7 until completion of 24 cycles of umbralisib (i.e. every other cycle for 18 cycles or 9 doses, for a total of 15 doses of rituximab), or until progression or intolerance. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Participants must have histologically confirmed follicular lymphoma grade 1-3A or marginal zone lymphoma by WHO criteria.
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter [LDi] to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥15 mm in LDi for nodal disease or >10 mm in LDi for extranodal lesions.
- Requires therapy based on: symptomatic disease, threatened end-organ dysfunction, compressive disease, cytopenias secondary to lymphoma, bulky disease (defined as any site ≥7 cm, or 3 or more sites ≥3cm), or steady progression.
- For patients with follicular lymphoma: No prior systemic therapy for follicular lymphoma. Prior radiation to a single site of disease is allowed if completed at least 2 weeks prior to initiation of protocol therapy and there are additional sites of measurable disease outside of the radiation field.
- For patients with marginal zone lymphoma: No prior systemic therapy for marginal zone lymphoma. Prior radiation or surgical resection is allowed if there are additional sites of measurable disease outside of the radiation field. Prior radiation must be completed at least 2 weeks prior to initiation of protocol therapy. Prior H. pylori eradication therapy is allowed.
Key exclusion criteria (23 listed)
- Participants who require immediate cytoreduction per the treating investigator.
- For patients with H. pylori related gastric extranodal marginal zone lymphoma in the absence of t(11;18): Patient must have relapsed or refractory marginal zone lymphoma despite appropriate H. pylori eradication.
- For patients with hepatitis C virus related marginal zone lymphoma: Patient must have relapsed or refractory marginal zone lymphoma despite appropriate treatment of hepatitis C virus infection.
- Active systemic therapy for another malignancy within 2 years. Local/regional therapy with curative intent such as surgical resection or localized radiation is allowed if patient is deemed at low risk for recurrence by treating physician.
- Malignancy within 3 years of study enrollment except for adequately treated basal, squamous cell carcinoma or non-melanomatous skin cancer, carcinoma in situ of the cervix, superficial bladder cancer not treated with intravesical chemotherapy or BCG within 6 months, localized prostate cancer and PSA <1.0 mg/dL on 2 consecutive measurements at least 3 months apart with the most recent one being within 4 weeks of study entry.
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 |
|---|---|---|
| UmbralisibAlso: TGR-1202Umbralisib is an investigational drug which blocks a protein called PI3K. PI3K is a protein that plays a role in the way cells grow. In this type of cancer, PI3K is increased and more active than usual. This helps the cancer cells to grow and survive. | Drug | Umbralisib+Rituximab |
| RituximabAlso: MabTheraRituximab works by targeting the CD20 antigen on normal and malignant B-cells. Then the body's natural immune defenses are recruited to attack and kill the marked B-cells | Drug | Umbralisib+Rituximab |
Primary outcome
Complete Response Rate
Time frame: 2 years
The frequency of patients who achieve a complete response per 2014 Lugano criteria.
4 secondary outcomes
Overall Response Rate
Time frame: 2 years
Progression Free Survival
Time frame: 2 years
Overall Survival
Time frame: 2 Years
Number of Participants With Adverse Events
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Link to MGH Center for LymphomaLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
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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.
Jacob D. Soumerai, MD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Umbralisib and Rituximab in people with Lymphoma and Follicular Lymphoma, run by Massachusetts General Hospital at 2 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 17 inclusion and 23 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: stopped early, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 27 Feb 2026). 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?
Complete Response Rate (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Feb 2026.