Clinical Trials /

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

NCT03919175

Description:

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

Related Conditions:
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Umbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma
  • Official Title: A Phase 2 Study of Umbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 19-011
  • NCT ID: NCT03919175

Conditions

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

Interventions

DrugSynonymsArms
UmbralisibTGR-1202Umbralisib+Rituximab
RituximabMabTheraUmbralisib+Rituximab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Umbralisib+RituximabExperimentalA 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.
  • Umbralisib
  • Rituximab

Eligibility Criteria

        Inclusion Criteria:

          -  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)

          -  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.

        Exclusion Criteria:

          -  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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response Rate
Time Frame:2 years
Safety Issue:
Description:The frequency of patients who achieve a complete response

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:The frequency of patients who achieve a complete or partial response
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:The median progression-free survival using Kaplan-Meier method with time of registration as time origin.
Measure:Overall Survival Rate
Time Frame:2 Years
Safety Issue:
Description:The median overall survival using Kaplan-Meier method with time of registration as time origin.
Measure:Safety and Adverse Events: frequency, severity, and timing of adverse events
Time Frame:2 years
Safety Issue:
Description:The nature, frequency, severity, and timing of adverse events

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Lymphoma
  • Follicular Lymphoma
  • Marginal Zone Lymphoma

Last Updated

April 18, 2019