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Recurrent Follicular LymphomaPhase 1/2NCT05152459

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

A Phase 1/2 study testing Tazemetostat, Ublituximab and Umbralisib in people with Recurrent Follicular Lymphoma and Refractory Follicular Lymphoma, run by City of Hope Medical Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tazemetostat, Ublituximab and Umbralisib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
1 May 2023to 15 Dec 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • 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
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  • 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
  • NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement.
  • Hemoglobin >= 8 g/dL
  • NOTE: No erythropoietin and/or packed red blood cells (pRBC) transfusion allowed within 7 days prior to screening)
  • Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease or hepatic involvement by lymphoma)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN
  • Alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula
  • Women of childbearing potential (WOCBP): negative serum pregnancy test within 3 days prior to cycle 1 day 1
  • Agreement by females of childbearing potential* to use 2 reliable methods of contraception simultaneously (including one highly effective and one effective contraceptive method) and males (including those who have had a vasectomy) to use an highly effective method of birth control, or abstain from heterosexual activity for the course of the study starting from at least 28 days prior to initiating tazemetostat for women, and 7 days prior to initiating tazemetostat for men, through at least 6 months after the last dose of tazemetostat for women and 3 months for men, and at least 4 months after the last dose of ublituximab or umbralisib, whichever comes later, for both men and women
  • Childbearing potential defined as not being surgically sterilized (women) or have not been free from menses for > 1 year (women only).

Who cannot join

  • 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).
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  • 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
  • Clinically significant uncontrolled illness, including active infection requiring antibiotics
  • Live virus vaccines within 4 weeks of start of protocol therapy or planned administration of live virus vaccines during ublituximab therapy
  • 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), or active cytomegalovirus (CMV). If hepatitis B virus core (HBc) antibody is positive, the subject must be evaluated for the presence of HBV deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR). If HCV antibody is positive, the subject must be evaluated for the presence of HCV ribonucleic acid (RNA) by PCR. If the subject is CMV IgG or CMV IgM positive, the subject must be evaluated for the presence of CMV DNA by PCR. Subjects with positive HBc antibody and negative HBV DNA by PCR are eligible. Subjects with positive HCV antibody and negative HCV RNA by PCR are eligible. Subjects who are CMV IgG or CMV IgM positive but who are CMV DNA negative by PCR are eligible. Patients with a prior known history of hepatitis B and those with a positive anti-HBc with negative hepatitis B surface antigen (HBsAg) at screening must be able to receive antiviral agents effective against hepatitis B such as, but not limited to, enofovir or entecavir
  • Known history of human immunodeficiency virus (HIV) infection
  • Females only: Pregnant or breastfeeding
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

About this study

Official title: A Phase 1/2 Study of Tazemetostat With Umbralisib and Ublituximab in Patients With Relapsed/Refractory Follicular Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the safety and tolerability of a regimen combining tazemetostat, umbralisib and ublituximab in patients with relapsed/refractory follicular lymphoma (FL).

II. Estimate the overall response rate (ORR) in relapsed/refractory FL patients treated with tazemetostat, umbralisib and ublituximab.

SECONDARY OBJECTIVE:

  1. Estimate the complete response (CR) rate, time to response, duration of response (DOR), overall survival (OS) and event-free survival (EFS) in relapsed/refractory FL patients treated with tazemetostat, umbralisib and ublituximab.

EXPLORATORY OBJECTIVES:

  1. Examine the immune effects of concurrent targeting of PI3K and EZH2 in patients with FL. II. Examine the evolution of tumor genetic profile while on therapy with tazemetostat, umbralisib and ublituximab, as determined by liquid biopsy.

OUTLINE: This is a phase I, dose-escalation study of tazemetostat and umbralisib followed by a phase II trials.

Patients receive ublituximab intravenously (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 orally (PO) twice daily (BID) umbralisib by PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 months for 2 years.

Being tested
Tazemetostat, Ublituximab, Umbralisib
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TazemetostatDrug

    Also called E7438, EPZ-6438, EPZ6438

    Given PO

  • UblituximabBiological

    Also called LFB-R603, TG-1101, TG-20, TGTX-1101

    Given IV

  • UmbralisibDrug

    Also called 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

    Given PO

Study groups in NCT05152459
Study groupRoleWhat they receive
Treatment (tazemetostat, umbralisib, ublituximab)ExperimentalPatients 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.
Receives: Drug: Tazemetostat; Biological: Ublituximab; Drug: Umbralisib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 28 days (1 cycle)

  2. 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.

    Measured: Up to 2 years

Secondary outcomes (5)

  1. Complete response rate

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

    Measured: Up to 2 years

  2. Time to response

    Will be summarized among those achieving CR/PR using descriptive statistics.

    Measured: Up to 2 years

  3. Duration of response

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.

    Measured: Up to 2 years

  4. Overall survival

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.

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

  5. Event-free survival

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2021
  2. Study start1 May 2023 (estimated)
  3. Primary completion15 Dec 2024 (estimated)
  4. Study completion15 Dec 2024 (estimated)

Why it stopped: Feasibility

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05152459
Sponsor's protocol ID
21303
Other IDs
NCI-2021-12560, 21303, P30CA033572
Status last verified
May 2023
First submitted
26 Nov 2021
Last updated
31 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tazemetostat, Ublituximab and Umbralisib in people with Recurrent Follicular Lymphoma and Refractory Follicular Lymphoma, run by City of Hope Medical Center.

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 25 inclusion and 22 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: withdrawn, as of the sponsor's last update on 31 May 2023. Status can change between updates, so confirm with the study contact before making plans.

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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Dose-limiting toxicity (time frame: Up to 28 days (1 cycle)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05152459.

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 31 May 2023.

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