Umbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma

NCT03919175 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-011
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This research is being done to assess Umbralisib and Rituximab as a first line therapy for Follicular Lymphoma or Marginal Zone Lymphoma.

Conditions

Lymphoma; Follicular Lymphoma; Follicular Lymphoma, Grade 1; Follicular Lymphoma Grade 2; Follicular Lymphoma Grade IIIa; Marginal Zone Lymphoma; Marginal Zone B Cell Lymphoma

Keywords

Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate

  The frequency of patients who achieve a complete response per 2014 Lugano criteria.

  2 years

Secondary Outcomes (4)

• Overall Response Rate

  2 years

• Progression Free Survival

  2 years

• Overall Survival

  2 Years

• Number of Participants With Adverse Events

  2 years

Study Arms (1)

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.

Drug: Umbralisib; Drug: Rituximab

Interventions

Umbralisib DRUG

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.

Also known as: TGR-1202

Umbralisib+Rituximab

Rituximab DRUG

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

Also known as: MabThera

Umbralisib+Rituximab

Eligibility Criteria

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

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• TG Therapeutics: collaborator

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconness Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Links

• Link to MGH Center for Lymphoma

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone

Interventions

umbralisib; Rituximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jacob D. Soumerai, MD; Associate Professor of Medicine
• Organization: Massachusetts General Hospital

jsoumerai@mgh.harvard.edu

617-792-0547

Study Officials

• Jacob D. Soumerai, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 18, 2019
• Study Start: September 1, 2019
• Primary Completion: May 5, 2024
• Study Completion: May 5, 2024
• Last Updated: February 27, 2026
• Results First Posted: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)