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

Epizyme

Status and phase: Withdrawn; Phase 2; Phase 1

Conditions: Refractory Hematologic Malignancy; Relapsed Hematologic Malignancy

Treatments: Drug: Tazemetostat; Drug: Acalabrutinib; Drug: Daratumumab (Intravenously); Drug: Lenalidomide; Drug: Tafasitamab; Drug: Pomalidomide; Drug: Dexamethasone 20mg; Drug: Mosunetuzumab; Drug: Daratumumab (Subcutaneously); Drug: Hyaluronidase-Fihj

Study type: Interventional

Funder types: Industry

Identifiers

NCT05205252

EZH-1501

Details and patient eligibility

About

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.

Full description

This phase 1b/2 trial studies how safely the EZH2 inhibitor tazemetostat works with other therapies in various hematological malignancies. Tazemetostat has been found to be a safe and effective drug that works in patients with relapsed refractory (R/R) follicular lymphoma. Giving tazemetostat in combination with other treatments may work better in treating patients with hematological malignancies and may improve disease response and durability of response.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Presence or history of central nervous system involvement by lymphoma

2. Less than minimum washout period of prior anticancer therapy as specified by the protocol

3. Prior allogeneic haematopoietic stem cell transplantation

4. History of solid organ transplant

5. Major surgery within 4 weeks of the start of study drug.

6. Significant cardiac or cardiovascular impairment as specified by protocol

7. Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat

8. History of any bleeding disorder, peptic ulcer disease, or significant bleeding within the last 1 month prior to enrollment

9. Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition

10. Patients with known active infection, or reactivation of a latent infection, as specified by the protocol

11. Known sensitivity or allergy to the study medications

12. Unwilling to refrain from eating or drinking grapefruit juice, Seville oranges, and grapefruits while on study

13. Prior exposure to tazemetostat

14. 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.

15. Prior history of myeloid malignancies or T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL)

16. For patients with DLBCL in Arm 1 (tazemetostat plus tafasitamab plus lenalidomide) or Arm 2 (tazemetostat plus lenalidomide):

    • Prior exposure to lenalidomide

17. For patients with MCL in Arm 3 (tazemetostat plus acalabrutinib):

    • Prior exposure to a BTKi
    • Medical condition that would make treatment with a BTKi not reasonable (e.g. allergy to BTKi or mutations known not to respond to BTKi treatment or subjects unable to be transitioned off of proton pump inhibitors)

18. For patients with MM in Arm 4:

    • Prior exposure to pomalidomide
    • Untreated or impending spinal cord compression in subjects

19. For patients with FL in Arm 5:

    • Grade 3b, mixed histology, or FL that has histologically transformed to DLBCL.
    • History of significant neurological disorders, hemophagocytic lymphohistiocytosis (HLH), chronic active Epstein-Barr virus (EBV) infection, progressive multifocal leukoencephalopathy (PML), lung disease (ILD), drug-induced pneumonitis, autoimmune pneumonitis, and/or history of severe autoimmune disease

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 5 patient groups

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

Active Comparator group

Description:

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.

Treatment:

Drug: Tazemetostat

Drug: Tafasitamab

Drug: Lenalidomide

Arm 2-Tazemetostat plus lenalidomide

Active Comparator group

Description:

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

Treatment:

Drug: Tazemetostat

Drug: Lenalidomide

Arm 3- Tazemetostat plus BTKi (acalabrutinib)

Active Comparator group

Description:

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

Treatment:

Drug: Tazemetostat

Drug: Hyaluronidase-Fihj

Drug: Acalabrutinib

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

Active Comparator group

Description:

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.

Treatment:

Drug: Pomalidomide

Drug: Dexamethasone 20mg

Drug: Tazemetostat

Drug: Daratumumab (Intravenously)

Drug: Daratumumab (Subcutaneously)

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

Active Comparator group

Description:

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

Treatment:

Drug: Tazemetostat

Drug: Mosunetuzumab