Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Amino Acids

Dexamethasone

Acalabrutinib

Lenalidomide

Daratumumab

Pomalidomide

Dexamethasone acetate

Tyrosine Kinase Inhibitors

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

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

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

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.

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

Orally, twice daily in continuous 28-day cycles.

Tazemetostat

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.

Tafasitamab

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.

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.

Daratumumab (Intravenously)

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.

Mosunetuzumab

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.

Daratumumab (Subcutaneously)

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.

Hyaluronidase-Fihj

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

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

Dexamethasone 20mg

Ipsen Medical Director

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.

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.

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

ARIA: A Phase 1b/2, Open-label, Multi Cohort Trial of Tazemetostat in Combination With Various Treatments in Subjects With Relapsed or Refractory Hematologic Malignancies

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).

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).

Progression free survival is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause.

Defined as the time from the first dose of study drug to the earliest date of CR or PR per Lugano Classification (Arms 1, 2, 3, and 5) or sCR, CR, VGPR, or PR per IMWG 2016 criteria (Arm 4) as assessed by Investigator review.

Duration of response is defined as the time from the initial response (at least partial remission) to documented disease progression.

Defined as the percentage of participants who achieve complete response (CR), partial response (PR), or stable disease per Lugano Classification (Arms 1, 2, 3, or 5) or stringent complete response (sCR), CR, very good partial response (VGPR), PR, or stable disease per IMWG 2016 criteria (Arm 4) at 6 months on study treatment, as assessed by Investigator review.

Overall survival is defined as the time from the first dose of study drug to date of death due to any cause.

Defined as the time from the first dose of study drug to the start of subsequent anticancer therapy

An Adverse Event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Percentage of participants with clinically significant changes in laboratory parameters including, hematology, serum chemistry, coagulation and urinalysis will be reported. The clinical significance will be evaluated by the investigator.

Epizyme, Inc.

Symptoms and General Pathology

Immune System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Mastocytosis

Leukemia

Leukemia, Myeloid

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Hairy Cell

Mastocytosis, Systemic

Acute Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Mast Cell Activation Disorders

Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Hairy Cell Leukemia

Systemic Mastocytosis

Dendritic Cell Tumor

Blastic Plasmacytoid Dendritic Cell

Chronic Myeloproliferative Disorders

Antipyretics

Analgesics

Antirheumatic Agents

Anti-Allergic Agents

Central Nervous System Depressants

Dermatologic Agents

Anti-Infective Agents

Acetaminophen

Ibuprofen

BB 1101

Antibodies, Bispecific

Diphenhydramine

Promethazine

Ichthammol

Ranitidine

Ranitidine bismuth citrate

Immunoglobulins, Intravenous

HIV Protease Inhibitors

Protease Inhibitors

Analgesics, Non-Narcotic

Anti-Inflammatory Agents, Non-Steroidal

Cyclooxygenase Inhibitors

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Antacids

Anti-Ulcer Agents

Histamine H2 Antagonists

INDUCTION THERAPY: Patients receive flotetuzumab via continuous IV infusion on days 1-28. Patients who achieve SD/PR (Cohort A) or PR/CI (Cohort B), receive an additional induction cycle. Patients who achieve PR (Cohort A) or PR/CI/MMR (Cohort B) after cycle 2 re-induction, may continue induction therapy for up to 4 more cycles.

CONSOLIDATION THERAPY: Patients who achieve CR/CRi/CRh/MLFS (Cohort A) or CR/MR (Cohort B) after cycle 1 or cycle 2 of induction therapy, receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 and 6 cycles, respectively, in the absence of disease progression or unacceptable toxicity. Patients with PR (Cohort A) or PR/CI/MMR (Cohort B) who have received up to 6 cycles of induction therapy may receive up to 2 cycles of consolidation therapy in the absence of disease progression or unacceptable toxicity.

Flotetuzumab

Ibrahim T Aldoss

This phase I trial studies the best dose and side effects of flotetuzumab for the treatment of patients with blood cancers (hematological malignancies) that have spread to other places in the body (advanced) and have come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Flotetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (recommended phase 2 dose, RP2D) of flotetuzumab, when given as a single agent.

II. Evaluate the safety and tolerability of flotetuzumab in CD123-positive advanced acute lymphoblastic leukemia (ALL) (Cohort A) and other hematological malignancies (Cohort B), by evaluation of toxicities including: type, frequency, severity, attribution, and duration of the toxicity.

SECONDARY OBJECTIVES:

I. Obtain preliminary estimates of remission; (complete remission \[CR\], complete remission with incomplete count recovery \[CRi\], complete remission with partial hematological recovery \[CRh\] or morphologic leukemia free state \[MLFS\] in Cohort A or CR/molecular response \[MR\] in Cohort B) rate and duration.

II. Estimate 1-year overall survival. III. Evaluate minimal residual disease (MRD) status in responders in the ALL cohort.

IV. Evaluate the percentage of patients who receive subsequent allogeneic transplantation.

EXPLORATORY OBJECTIVES:

I. Examine immune profile pre- and post-treatment with flotetuzumab. II. Assess the association between CD123 expression and tumor response. III. Assess the association between alterations in tumor genetic or microenvironment with response.

IV. Assess cytokine levels during therapy.

OUTLINE: This is a dose-escalation study.

INDUCTION THERAPY: Patients receive flotetuzumab via continuous intravenous (IV) infusion on days 1-28. Patients who achieve stable disease (SD)/partial remission (PR) (Cohort A) or PR/clinical improvement (CI) (Cohort B), receive an additional induction cycle. Patients who achieve PR (Cohort A) or PR/CI/major molecular response (MMR) (Cohort B) after cycle 2 re-induction, may continue induction therapy for up to 4 more cycles.

CONSOLIDATION THERAPY: Patients who achieve CR/CRi/CRh/MLFS (Cohort A) or CR/MR (Cohort B) after cycle 1 or cycle 2 of induction therapy, receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 and 6 cycles, respectively, in the absence of disease progression or unacceptable toxicity. Patients with PR (Cohort A) or PR/CI/MMR (Cohort B) who have received up to 6 cycles of induction therapy may receive up to 2 cycles of consolidation therapy in the absence of disease progression or unacceptable toxicity.

SUPPORTIVE CARE: Patients also receive acetaminophen orally (PO) or ibuprofen PO every 8 hours for 48 hours, diphenhydramine or equivalent IV or PO every 8 hours for 48 hours, ranitidine or equivalent IV every 8 hours for 48 hours, and dexamethasone IV up to 30 minutes prior to dosing and then at 12 hours after dosing on week 1 days 1 and 7.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year.

Flotetuzumab for the Treatment of Relapsed or Refractory Advanced CD123-Positive Hematological Malignancies

A Phase 1 Trial to Evaluate the Safety of Single Agent Flotetuzumab in Advanced CD123-Positive Hematological Malignancies

Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0 except infusion-related reaction (IRR)/cytokine release syndrome (CRS) which will be by the modified criteria proposed by Lee et al. Safety and toxicity will be assessed for each cohort independently. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, probable association with the study treatment and reversibility or outcome.

Rates and 95% Clopper Pearson binomial confidence interval (CI) will be calculated for complete remission/response rate (confirmed complete remission \[CR\]/ complete remission with incomplete count recovery \[CRi\]/ complete remission with partial hematological recovery \[CRh\] \[Cohort A\] or CR/molecular response \[MR\] \[Cohort B\]). Remission rates will also be explored based on number/type of prior therapy(ies), the presence of extramedullary disease at the time of starting therapy, disease burden, and CD123 expression intensity.

Assessed by multi-color flow cytometry in ALL the cohorts.

Will be estimated using the product-limit method of Kaplan and Meier.

Number/percent of patients who proceed to hematopoietic cell transplantation after achieving complete response/ complete remission

National Cancer Institute (NCI)

City of Hope Medical Center

Syndrome

Leukemia, Myeloid, Acute

Sarcoma

Preleukemia

Myelodysplastic Syndromes

Leukemia, Myelomonocytic, Juvenile

Sarcoma, Myeloid

Lymphoma, Non-Hodgkin

Precancerous Conditions

Myelodysplastic-Myeloproliferative Diseases

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Soft Tissue Sarcoma

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Myeloid Sarcoma

Myelodysplastic/myeloproliferative Disease

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Rituximab

Melphalan

Lenograstim

Thiotepa

Interleukin-2

Mechlorethamine

Antilymphocyte Serum

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Antimetabolites

Antiviral Agents

Anti-HIV Agents

Anti-Retroviral Agents

Phenylalanine

Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Tazemetostat in Combination With Various Treatments in Participants With Blood Cancer.	NCT05205252	Relapsed Hemato... Refractory Hema...	Tazemetostat Tafasitamab Lenalidomide Acalabrutinib Daratumumab (In... Mosunetuzumab Daratumumab (Su... Hyaluronidase-F... Pomalidomide Dexamethasone 2...	18 Years -	Ipsen
Flotetuzumab for the Treatment of Relapsed or Refractory Advanced CD123-Positive Hematological Malignancies	NCT04681105	Recurrent Acute... Recurrent B Acu... Recurrent Blast... Recurrent Chron... Recurrent Hairy... Recurrent Hemat... Recurrent Hodgk... Recurrent T Acu... Refractory Acut... Refractory B Ac... Refractory Blas... Refractory Chro... Refractory Hair... Refractory Hema... Refractory Hodg... Refractory T Ac... Systemic Mastoc...	Acetaminophen Dexamethasone Diphenhydramine Flotetuzumab Ibuprofen Ranitidine	12 Years -	City of Hope Medical Center
Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation	NCT02259348	Acute Lymphobla... Acute Myeloid L... Myeloid Sarcoma Chronic Myeloge... Juvenile Myelom... Myelodysplastic... Non-Hodgkin Lym...	Cyclophosphamid... Fludarabine G-CSF Interleukin-2 Melphalan Thiotepa Rituximab Natural killer ... T-cell depleted... CD45RA-depleted...	- 21 Years	St. Jude Children's Research Hospital
A Study of CA-4948 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma	NCT03328078	Relapsed Hemato... Refractory Hema... Relapsed Primar... Refractory Prim...	Emavusertib ibrutinib	18 Years -	Curis, Inc.

Spots Global Cancer Trial Database for refractory hematologic malignancy