A Study of Tazemetostat in Combination With Various Treatments in Participants With Blood Cancer.

NCT05205252 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: EZH-1501
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

This trial will study how safely the tazemetostat works with other therapies in various hematological malignancies. Hematologic malignancies are cancers that most often begin in the bone marrow or lymph nodes where blood precursors are produced. They are often called blood cancers and fall into three categories: leukemia, lymphoma and myeloma. Tazemetostat has been found to be a safe and effective drug that works in patients with follicular lymphoma where the disease has come back after treatment (known as relapsed) and when other treatment no longer works (known as refractory). Combining tazemetostat with other treatments may work better in treating patients with hematological malignancies and may improve disease response and durability of response.

Conditions

Relapsed Hematologic Malignancy; Refractory Hematologic Malignancy

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Recommended Phase 2 Dose (RP2D) of tazemetostat in combination with each partner drug

  The safety and tolerability of tazemetostat in combination with each partner drug in participants with R/R malignancies will be evaluated. RP2D of tazemetostat for further evaluation in phase 2 will be selected as assessed by the occurrence of treatment-emergent dose-limiting toxicities (DLTs) and adverse events (AEs).

  Evaluated for DLTs during the first 28-day cycle. The RP2D for Phase 2 for each arm will be selected at the end of that arm's experience in Phase 1b

• Phase 2: Objective Response Rate (ORR)

  Overall response rate is defined as proportion of participants with a best response of at least partial remission (including partial remission and complete remission for participants with non-Hodgkin lymphoma in Arms 1, 2, 3, or 5 or partial remission, complete remission, stringent complete response, or very good partial response).

  Time from the date of first dose of study drug to the time of response, assessed up to 24 months.

Secondary Outcomes (8)

• Phase 2: Progression Free Survival (PFS)

  Up to 24 months.

• Time to response (TTR)

  Up to 24 months

• Phase 2: Duration of Response (DOR)

  Up to 24 months

• Phase 2: Disease control rate (DCR)

  Up to 24 months

• Phase 2: Overall Survival (OS)

  Up to 24 months

Study Arms (5)

Arm 1-Tazemetostat plus tafasitamab-cxix (CD19 Ab)/lenalidomide

ACTIVE COMPARATOR

Participants with R/R, diffuse large B-cell lymphoma (DLBCL) will receive tazemetostat, tafasitamab, and lenalidomide for approximately 1 year. After approximately 1 year, participants will receive tazemetostat and tafasitamab.

Drug: Tazemetostat; Drug: Tafasitamab; Drug: Lenalidomide

Arm 2-Tazemetostat plus lenalidomide

ACTIVE COMPARATOR

Participants with R/R DLBCL will receive tazemetostat and lenalidomide for approximately 1 year. After approximately 1 year, participants will receive tazemetostat alone.

Drug: Tazemetostat; Drug: Lenalidomide

Arm 3- Tazemetostat plus BTKi (acalabrutinib)

ACTIVE COMPARATOR

Participants with R/R mantle cell lymphomawill (MCL) will receive tazemetostat and acalabrutinib for the entire study.

Drug: Tazemetostat; Drug: Acalabrutinib; Drug: Hyaluronidase-Fihj

Arm 4-Tazemetostat plus CD38 mAbPD (daratumumab/pomalidomide/dexamethasone)

ACTIVE COMPARATOR

Participants with R/R multiple myelomawill (MM) will receive tazemetostat, daratumumab, pomalidomide, and dexamethasone for the entire study. Daratumumab may be given intravenously or subcutaneously during this study.

Drug: Tazemetostat; Drug: Daratumumab (Intravenously); Drug: Daratumumab (Subcutaneously); Drug: Pomalidomide; Drug: Dexamethasone 20mg

Arm 5- Tazemetostat plus CD20/CD3 BsAb (mosunetuzumab)

ACTIVE COMPARATOR

Participants with R/R follicular lymphoma will receive tazemetostat and mosunetuzumab for approximately 1 year. After approximately 1 year, participants will receive tazemetostat alone.

Drug: Tazemetostat; Drug: Mosunetuzumab

Interventions

Tazemetostat DRUG

Orally, twice daily in continuous 28-day cycles.

Also known as: IPN60200

Arm 1-Tazemetostat plus tafasitamab-cxix (CD19 Ab)/lenalidomide; Arm 2-Tazemetostat plus lenalidomide; Arm 3- Tazemetostat plus BTKi (acalabrutinib); Arm 4-Tazemetostat plus CD38 mAbPD (daratumumab/pomalidomide/dexamethasone); Arm 5- Tazemetostat plus CD20/CD3 BsAb (mosunetuzumab)

Tafasitamab DRUG

Intravenously, 12 mg/kg, once daily on Cycle 1: Days 1, 4, 8, 15 and 22 of the 28-day cycle. Cycles 2 and 3: Days 1, 8, 15 and 22 of each 28-day cycle. Cycle 4 and beyond: Days 1 and 15 of each 28-day cycle.

Arm 1-Tazemetostat plus tafasitamab-cxix (CD19 Ab)/lenalidomide

Lenalidomide DRUG

Orally, 10 mg or 20 mg based on kidney function, once daily from Days 1 to 21 of continuous 28-day cycles for up to 12 cycles.

Arm 1-Tazemetostat plus tafasitamab-cxix (CD19 Ab)/lenalidomide; Arm 2-Tazemetostat plus lenalidomide

Acalabrutinib DRUG

Orally, 100 mg, twice daily.

Also known as: Bruton tyrosine kinase inhibitor

Arm 3- Tazemetostat plus BTKi (acalabrutinib)

Daratumumab (Intravenously) DRUG

Intravenously, 16 mg/kg actual body weight, once daily on Cycles 1 and 2: Days 1, 8, 15 and 22 of the 28-day cycle. Cycles 3 through 6: Days 1 and 15 each 28-day cycle. Cycle 7 and beyond: Day 1 of each 28-day cycle.

Arm 4-Tazemetostat plus CD38 mAbPD (daratumumab/pomalidomide/dexamethasone)

Mosunetuzumab DRUG

Subcutaneously, step-up doses on Cycle 1 Days 1 (5 mg), 8 (45 mg) and 15 (45 mg) and then 45 mg from Cycle 2 through 12 on Day 1 of the 28-day cycle.

Arm 5- Tazemetostat plus CD20/CD3 BsAb (mosunetuzumab)

Daratumumab (Subcutaneously) DRUG

Subcutaneously, 1800 mg, once daily on Cycles 1 and 2: Days 1, 8, 15 and 22 of the 28-day cycle. Cycles 3 through 6: Days 1 and 15 each 28-day cycle. Cycle 7 and beyond: Day 1 of each 28-day cycle.

Arm 4-Tazemetostat plus CD38 mAbPD (daratumumab/pomalidomide/dexamethasone)

Hyaluronidase-Fihj DRUG

Subcutaneously, 30,000 units, once daily on Cycles 1 and 2: Days 1, 8, 15 and 22 of the 28-day cycle. Cycles 3 through 6: Days 1 and 15 each 28-day cycle. Cycle 7 and beyond: Day 1 of each 28-day cycle.

Arm 3- Tazemetostat plus BTKi (acalabrutinib)

Pomalidomide DRUG

Orally, 4 mg, once daily on Days 1 to 21 of continuous 28-day cycles.

Arm 4-Tazemetostat plus CD38 mAbPD (daratumumab/pomalidomide/dexamethasone)

Dexamethasone 20mg DRUG

Orally, 20 mg or 40 mg, once daily on Days 1, 8, 15, and 22 of continuous 28-day cycles.

Arm 4-Tazemetostat plus CD38 mAbPD (daratumumab/pomalidomide/dexamethasone)

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 for Phase 1b and status 0 to 2 for Phase 2
• Must have documented relapsed, refractory, or progressive disease after 2 lines of treatment with systemic therapy
• Measurable disease
• Demonstrate adequate organ function
• Negative test results for acute or chronic hepatitis B virus (HBV) infection, hepatitis C virus (HCV) and human immunodeficiency virus
• No ongoing clinically significant reactions to prior anticancer treatments
• Willingness to follow pregnancy precautions and register into the mandatory REMS program in lenalidomide and pomalizdomide arms

You may not qualify if:

• Presence or history of central nervous system involvement by lymphoma
• Less than minimum washout period of prior anticancer therapy as specified by the protocol
• Prior allogeneic haematopoietic stem cell transplantation
• History of solid organ transplant
• Major surgery within 4 weeks of the start of study drug.
• Significant cardiac or cardiovascular impairment as specified by protocol
• Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat
• History of any bleeding disorder, peptic ulcer disease, or significant bleeding within the last 1 month prior to enrollment
• Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition
• Patients with known active infection, or reactivation of a latent infection, as specified by the protocol
• Known sensitivity or allergy to the study medications
• Unwilling to refrain from eating or drinking grapefruit juice, Seville oranges, and grapefruits while on study
• Prior exposure to tazemetostat
• Any condition that places the subject at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study.
• Prior history of myeloid malignancies or T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL)

Sponsors & Collaborators

• Epizyme, Inc.: lead

Study Sites (3)

California Cancer Associates For Research And Excellence, cCARE

Santa Fe, California, 92024, United States

Location

Central Care Cancer Center

Bolivar, Missouri, 65613, United States

Location

Astera Cancer Center

East Brunswick, New Jersey, 08816, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

tazemetostat; tafasitamab; Lenalidomide; acalabrutinib; daratumumab; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: December 29, 2021
• First Posted: January 25, 2022
• Study Start: December 22, 2021
• Primary Completion: July 5, 2023
• Study Completion: July 5, 2023
• Last Updated: August 15, 2023

Record last verified: 2023-08

Locations

US (3)