Tazemetostat in Combination With Umbralisib and Ublituximab for the Treatment Relapsed or Refractory Follicular Lymphoma

NCT05152459 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: 21303NCI-2021-12560P30CA033572
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I/II trial tests the safety, side effects, and best dose of tazemetostat and umbralisib and whether tazemetostat in combination with umbralisib and ublituximab works to shrink tumors in patients with follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractor). Tazemetostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Umbralisib may help block the formation of growths that may become cancer. Ublituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving tazemetostat in combination with umbralisib and ublituximab may work better in treating follicular lymphoma.

Conditions

Recurrent Follicular Lymphoma; Refractory Follicular Lymphoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity

  Assessed by Common Terminology Criteria for Adverse Events version 5.0. Summarized by type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment, and reversibility or outcome.

  Up to 28 days (1 cycle)

• Overall response rate

  Will be estimated by the proportion of response-evaluable patients achieving complete response (CR) or partial response (PR, along with the 95% exact binomial confidence interval.

  Up to 2 years

Secondary Outcomes (5)

• Complete response rate

  Up to 2 years

• Time to response

  Up to 2 years

• Duration of response

  Up to 2 years

• Overall survival

  From start of protocol treatment to time of death due to any cause, assessed up to 2 years

• Event-free survival

  From start of protocol treatment to time of disease relapse/progression, start of non-protocol anti-lymphoma therapy due to toxicity of the protocol therapy, or death due to any cause, assessed up to 2 years

Study Arms (1)

Treatment (tazemetostat, umbralisib, ublituximab)

EXPERIMENTAL

Patients receive ublituximab IV on days 1, 8, and 15 of cycle 1, day 1 of cycle 2-6, and day 1 of every 3 cycles thereafter. Patients also receive tazemetostat PO BID umbralisib by PO QD on days 1-28. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Tazemetostat; Biological: Ublituximab; Drug: Umbralisib

Interventions

Tazemetostat DRUG

Given PO

Also known as: E7438, EPZ-6438, EPZ6438

Treatment (tazemetostat, umbralisib, ublituximab)

Ublituximab BIOLOGICAL

Given IV

Also known as: LFB-R603, TG-1101, TG-20, TGTX-1101

Treatment (tazemetostat, umbralisib, ublituximab)

Umbralisib DRUG

Given PO

Also known as: 2-((1S)-1-(4-Amino-3-(3-fluoro-4-(1-methylethoxy)phenyl)-1H-pyrazolo(3,4-d)pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-1-benzopyran-4-one, RP-5264, RP5264, TGR-1202

Treatment (tazemetostat, umbralisib, ublituximab)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Age: \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Histologically confirmed diagnosis of follicular lymphoma grade 1-3a according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution
• Relapsed/ refractory disease after at least 2 lines of systemic therapy including an anti-CD20 antibody. Relapse must have been confirmed histologically (with hematopathology review at the participating institution). Exceptions may be granted with study PI approval
• Active disease meeting requiring treatment per treating physician's decision
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy with one or more sites of disease \>= 1.5 cm in longest dimension
• Fully recovered from the acute toxic effects (except alopecia) to \<= Grade 1 to prior anti-cancer therapy
• Without bone marrow involvement: Absolute neutrophil count (ANC) \>=≥ 1,000/mm\^3
• NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement.
• With bone marrow involvement: ANC \>= 500/mm\^3
• NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement.
• Without bone marrow involvement: Platelets \>= 50,000/mm\^3
• NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement.
• With bone marrow involvement: Platelets \>= 30,000/mm\^3

You may not qualify if:

• Prior therapeutic intervention with any of the following: therapeutic anticancer antibodies within 3 weeks (rituximab); radio- or toxin-immunoconjugates within 10 weeks; all other chemotherapy or radiation therapy within 3 weeks prior to day 1 of protocol therapy.
• Prior exposure to either a PI3K inhibitor (including but not limited to idelalisib, duvelisib, copanlisib, and umbralisib) or an EZH2 inhibitor (including but not limited to tazemetostat).
• Prior allogeneic stem cell transplant
• Autologous hematologic stem cell transplant within 6 months of day 1 of protocol therapy
• Major surgical procedure (under general anesthesia) within 30 days of Day 1 of protocol therapy. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
• Chronic use of corticosteroids \>= 20 mg/day of prednisone or equivalent (short-term use of steroids \< 14 days is allowed).
• Requires treatment with a strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
• Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components
• Concurrent participation in another therapeutic clinical trial
• History of prior malignancy. Exceptions include malignancy treated with curative intent and no known active disease present for \>= 2 years prior to initiation of protocol therapy; adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease; adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease; asymptomatic prostate cancer managed with "watch and wait" strategy.
• Prior history of myeloid malignancies including myelodysplastic syndrome (MDS) or presence of cytogenetic and/or molecular abnormalities known to be associated with MDS or myeloproliferative neoplasms (MPN) (e.g. del 5q, chr 7 abn, JAK2 V617). Any evidence of clonal hematopoiesis in the screening bone marrow biopsy should be discussed with the study principal investigator (PI) prior to enrollment
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass
• Known active central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement
• Clinically significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class III or IV cardiac disease as defined by the New York Heart Association Functional Classification. Note Subjects with controlled, asymptomatic atrial fibrillation can enroll on study.
• Inability to swallow and retain an oral medication

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

tazemetostat; ublituximab; LFB-R603; umbralisib

Condition Hierarchy (Ancestors)

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

Study Officials

• Matthew Mei

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2021
• First Posted: December 9, 2021
• Study Start: May 1, 2023
• Primary Completion: December 15, 2024
• Study Completion: December 15, 2024
• Last Updated: May 31, 2023

Record last verified: 2023-05