Study Stopped
Investigational Drug removed from the market
Lenalidomide, Umbralisib, and Ublituximab for the Treatment of Relapsed or Refractory Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma
A Phase I Trial of Lenalidomide, Umbralisib and Ublituximab in Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma
2 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
This phase I trial studies the safety and how effective the combination of ublituximab, umbralisib, and lenalidomide is in certain types of indolent (slow-growing) non-Hodgkin's lymphoma or mantle cell lymphoma. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of non-Hodgkin's lymphoma by blocking blood flow to the cancer. Umbralisib is designed to block a protein called PI3 kinase in order to stop cancer growth and cause changes in the immune system that may allow the immune system to better act against cancer cells. Ublituximab is an antibody that attaches to the lymphoma cells and triggers immune reactions that may result in the death of the targeted lymphoma cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Sep 2022
Typical duration for phase_1
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 13, 2020
CompletedFirst Posted
Study publicly available on registry
November 19, 2020
CompletedStudy Start
First participant enrolled
September 30, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2024
CompletedSeptember 30, 2022
September 1, 2022
1.3 years
November 13, 2020
September 28, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Recommended phase 2 dose (RP2D)
Up to completion of cycle 2 (each cycle is 28 days)
Secondary Outcomes (5)
Duration of overall response
From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years
Overall response rate
Up to 2 years
Time to treatment failure
From study entry to discontinuation of treatment for any reason including disease progression, treatment toxicity, and death, assessed up to 2 years
Progression-free survival
From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years
Overall survival
From the start of treatment to death or censor at the last follow up, assessed up to 2 years
Study Arms (1)
Treatment (lenalidomide, umbralisib, ublituximab)
EXPERIMENTALPatients receive lenalidomide PO QD on days 1-21 and umbralisib PO QD on days 1-28. Beginning in cycle 2, patients also receive ublituximab IV over 90 minutes to 4 hours on day 1. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a partial or complete response after cycle 6 continue treatment of lenalidomide PO QD and umbralisib PO QD for 12 additional cycles, and ublituximab IV on day 1 of subsequent even cycles (8, 10, 12, 14, 16, and 18). Patients with stable disease after cycle 6 may continue on treatment for an additional 12 cycles at the discretion of the investigator.
Interventions
Given PO
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- Documentation of disease at diagnosis and/or relapse (local pathology review is allowed):
- Patients in the dose-escalation portion of the study must have histologically confirmed, low-grade B-cell NHL by the World Health Organization (WHO) classification:
- Follicular lymphoma (FL) grade 1, 2, or 3a
- Marginal zone B-cell lymphoma (MZL), including extranodal, nodal and splenic
- Lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia
- Mantle cell lymphoma (MCL)
- For the expansion cohort, patients must have histologically confirmed FL grade 1, 2, or 3a
- Patients with FL or MZL must have had at least one prior systemic therapy. Patients with MCL or LPL/Waldenström macroglobulinemia must have had prior treatment with at least 2 systemic treatments that included a BTK inhibitor (stopped due to progression or intolerance).
- Must be in need of treatment for relapsed or refractory disease as assessed by the investigator
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- Patients must have radiographically measurable disease
- Patients with LPL/Waldenstrom macroglobulinemia or MZL without radiographically measurable disease may be included if they have a measurable serum monoclonal protein (M protein)
- Absolute neutrophil count (ANC) \> 1,000/mcL
- Platelet count \> 75,000/mcL
- Total bilirubin =\< 1.5 x the upper limit of the normal range (ULN) (unless due to Gilbert's disease)
- +17 more criteria
You may not qualify if:
- Known or suspected active diffuse large B-cell lymphoma (DLBCL). Patients with prior history of DLBCL may be enrolled if their DLBCL has been previously treated and - in the opinion of the investigator - is not active
- Patients who have not recovered (i.e., \>= grade 2 toxicity) from adverse events due to agents administered more than 4 weeks earlier, and patients who have any grade pulmonary or related infections thought to be associated with pneumonitis, or any grade colitis
- Major surgery within 14 days before day 1, cycle 1 of treatment
- Radiotherapy within 14 days before day 1, cycle 1 of treatment
- Patients with prior systemic therapy must have had a minimum of 14 days from prior treatment with a BTK inhibitor, or 21 days from prior treatment with chemotherapy or any other therapy and day 1, cycle 1 of treatment. Concurrent glucocorticoid therapy as long as started for at least 7 days prior to study entry (=\< 20 mg per day of prednisone or equivalent) is allowed as clinically warranted
- Known central nervous system involvement. Subjects with symptoms of central nervous system (CNS) disease must have a negative computed tomography (CT) scan and negative diagnostic lumbar puncture
- Any prior use of lenalidomide
- Any prior use of idelalisib (CAL-101), duvelisib (IPI-145), copanlisib or any other drug that specifically inhibits phosphoinositide-3-kinase (PI3K)
- Prior allogeneic stem cell transplantation. Prior autologous stem cell transplant is allowed, if it was 6 months or longer ago
- Active systemic bacterial, fungal or viral infection except localized fungal infections of skin or nails. Patients with resolving infections such as urinary tract, respiratory, other than a respiratory infection thought to be associated with pneumonitis, or skin infections may be enrolled if clinically improving. NOTE: Subjects may be receiving prophylactic antiviral or antibacterial therapies at investigator discretion. Use of anti-pneumocystis and antiviral prophylaxis is required for subjects receiving umbralisib
- Patients with a history of deep vein thrombosis (DVT) or pulmonary embolus (PE) within 3 months before study entry are not eligible. Patients with history of DVT/PE greater than 3 months are eligible but recommended to receive aspirin, molecular weight heparin or direct thrombin inhibitor unless contraindicated
- Evidence of current uncontrolled or symptomatic cardiovascular conditions, including, uncontrolled cardiac arrhythmias, history of or symptomatic congestive heart failure (NYHA class II or greater), unstable angina, or myocardial infarction within the past 6 months. Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting within 6 months of enrollment. Concomitant use of medication known to cause QT prolongation or torsade de pointes should be used with caution and at investigator discretion
- Patients with history of autoimmune hepatitis, autoimmune or drug-induced colitis including inflammatory bowel disease (ulcerative colitis or Crohn's disease), and/or autoimmune or drug-induced pneumonitis
- Known history of drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, or cirrhosis of the liver
- Known gastrointestinal (GI) disease or gastrointestinal procedure that will significantly interfere with the oral absorption or tolerance of umbralisib or lenalidomide including inability to swallow pills/capsules
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Yazeed Sawalhalead
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yazeed Sawalha, MD
Ohio State University Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
November 13, 2020
First Posted
November 19, 2020
Study Start
September 30, 2022
Primary Completion
December 31, 2023
Study Completion
December 31, 2024
Last Updated
September 30, 2022
Record last verified: 2022-09
Data Sharing
- IPD Sharing
- Will not share