Zandelisib + Tazemetostat in R/R Follicular Lymphoma

NCT05604417 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 22-103
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This research study is being done to estimate the safety and efficacy of zandelisib and tazemetostat in people with relapsed or refractory follicular lymphoma (FL) This research study involves Zandelisib in combination with Tazemetostat. MEI Pharma, Inc, a biotechnology company, is supporting this research study by providing funding for the research study, including the study drug zandelisib.

Conditions

Relapsed Follicular Lymphoma; Refractory Follicular Lymphoma

Keywords

Relapsed Follicular Lymphoma; Refractory Follicular Lymphoma

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities Phase I

  Dose-limiting toxicity (DLT) is defined as an Adverse Event (AE) that meets all of the following criteria: Occurs during the 28 days of cycle 1 (DLT window); Is deemed at least possibly related to protocol therapy

  Up to 28 days

• Complete Response Rate Phase II

  response classified per the 2014 Lugano criteria

  up to 4 years

Secondary Outcomes (5)

• Overall Response Rate

  Up to 4 years

• Median Progression-Free Survival

  as the time from registration to the earlier of progression or death due to any cause up to 4 years

• Overall Survival

  as the time from registration to death due to any cause, or censored at date last known alive up to 4 years

• Duration of Response

  Up to 4 years

• Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  baseline up to 4 years

Study Arms (3)

PHASE 1: ZANDELISIB + TAZEMETOSTAT

EXPERIMENTAL

Phase 1 study (3+3 design), followed by a phase 2 expansion component * For phase 1 portion, which follows the same dosing schedule as Arm A, there will not be any randomization. * Zandelisib, oral, daily on predetermined days each cycle for a total of 14 cycles * Tazemetostat oral, twice daily on predetermined days (Cycles 1) and predetermined days (Cycles 2-14) for a total of 14 cycles. There will be 2 dose levels of tazemetostat.

Drug: TAZEMETOSTAT; Drug: Zandelisib

Arm A: COMBINATION ZANDELISIB + TAZEMETOSTAT

EXPERIMENTAL

Participants randomized into Arm A of the phase 2 component will receive * Zandelisib, oral, daily on predetermined days each cycle for a total of 14 cycles * Tazemetostat oral, twice daily on predetermined days (Cycles 1) and predetermined days (Cycles 2-14) for a total of 14 cycles

Drug: TAZEMETOSTAT; Drug: Zandelisib

Arm B: Zandelisib and Tazemetostat

EXPERIMENTAL

Participants randomized into Arm B of the phase 2 component will receive * Zandelisib oral, daily on predetermined days (Cycles 1-2) and predetermined days of cycle 3 and onwards up to 14 cycles. * Tazemetostat, oral, twice daily on predetermined days of each cycle. This will begin on cycle 3 and will continue for up to 12 cycles.

Drug: TAZEMETOSTAT; Drug: Zandelisib

Interventions

TAZEMETOSTAT DRUG

Dosage and treatment timings per protocol

Also known as: TAZVERIK

Arm A: COMBINATION ZANDELISIB + TAZEMETOSTAT; Arm B: Zandelisib and Tazemetostat; PHASE 1: ZANDELISIB + TAZEMETOSTAT

Zandelisib DRUG

Dosage and treatment timings per protocol

Also known as: ME-401

Arm A: COMBINATION ZANDELISIB + TAZEMETOSTAT; Arm B: Zandelisib and Tazemetostat; PHASE 1: ZANDELISIB + TAZEMETOSTAT

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 biopsy-proven relapsed or refractory FL grade 1-2 or 3A by WHO criteria.
• Participants must require therapy based on: symptomatic disease, threatened end-organ dysfunction, compressive disease, cytopenias secondary to lymphoma, bulky disease (defined as any site 7 cm or greater in size, or 3 or more sites 3 cm or greater in size), or progression.
• Participants must have received at least two prior systemic therapies for FL, or have relapsed or refractory FL who have no satisfactory alternative treatment options.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of zandelisib in combination with tazemetostat in participants \<18 years of age, children are excluded from this study.
• ECOG performance status ≤2 (Karnofsky ≥60%).
• Participants must have adequate marrow function as defined below (unless abnormalities are considered related to marrow and/or splenic involvement by lymphoma):
• absolute neutrophil count ≥1,000/mcL
• platelets ≥75,000/mcL
• Participants must have adequate organ function as defined below (unless abnormalities are considered related to target organ involvement or compression by lymphoma):
• total bilirubin ≤ 1.5x institutional upper limit of normal (ULN) (Isolated bilirubin ≤3.0x ULN is acceptable if considered secondary to Gilbert's syndrome)
• AST(SGOT)/ALT(SGPT) ≤2.0 × institutional ULN Creatinine clearance ≥50 mL/min eGFR (Cockcroft-Gault)
• Participants with known history or current symptoms of cardiac disease should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
• The effects of zandelisib and tazemetostat on the developing human fetus are unknown. A female participant is eligible to participate if she is not pregnant or breastfeeding. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for at least 4 months after the last dose of study intervention. Women must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Nonchildbearing potential is defined as follows (by other than medical reasons):
• ≥45 years of age and has not had menses for \>1 year
• Patients who have been amenorrhoeic for \<1 year without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation

You may not qualify if:

• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia. At the discretion of the overall PI, participants with residual toxicities \>Grade 1 may be considered eligible if in the opinion of the overall PI the residual toxicity is not likely to interfere with the safety or efficacy assessment of the investigational regimen.
• Participants who are receiving any other investigational agents.
• Participants must not have known central nervous system involvement by lymphoma.
• Participant must not have used an investigational drug or approved systemic lymphoma therapy with 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug. Steroids are permitted.
• Participant must not have received a PI3K inhibitor or EZH2 inhibitor.
• Participants must not have known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to zandelisib, tazemetostat, or drugs chemically related to zandelisib or tazemetostat, or any of the components of the study treatment.
• Participants must not have an uncontrolled intercurrent illness.
• Participants must not have an uncontrolled active infection.
• Participants must not have inflammatory bowel disease.
• Participants must not have active uncontrolled autoimmune disease.
• Participants must not have psychiatric illness/social situations that would limit compliance with study requirements. Participants must not have any serious and/or preexisting medical or other condition (including lab abnormalities) that could interfere with participant's safety in the opinion of the investigator.
• Women who are pregnant are excluded from this study because it is unknown if tazemetostat or zandelisib can cause embryo-fetal harm when administered to a pregnant woman. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with zandelisib and tazemetostat, breastfeeding should be discontinued if the mother is treated with zandelisib and tazemetostat.
• Participants must not have an active malignancy or systemic therapy for another malignancy within 3 years; local/regional therapy with curative intent such as surgical resection or localized radiation within 3 years of treatment is permitted; active prostate cancer that is considered low-risk and appropriate for continued active surveillance strategy is permitted. Additionally, adequately treated basal, squamous cell carcinoma, or non-melanomatous skin cancer, carcinoma in situ of the cervix, or superficial bladder cancer not treated with intravesical chemotherapy or BCG within 6 months, are permitted.
• Participant must be able to swallow pills.
• Participant must not have active uncontrolled HIV infection. Participants with HIV are eligible if disease is adequately controlled, defined by presence of both an undetectable viral load and a CD4 count \>200.

Sponsors & Collaborators

• Jacob Soumerai, MD: lead
• MEI Pharma, Inc.: collaborator

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

tazemetostat; ME-401

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

• Jacob D. Soumerai, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: October 28, 2022
• First Posted: November 3, 2022
• Study Start: January 1, 2023
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 7, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation