Symptoms and General Pathology

All Conditions

Neoplasms

Immune System Diseases

Blood and Lymph Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Mastocytosis

Leukemia

Leukemia, Myeloid

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Hematologic Neoplasms

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

Hematologic Diseases

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

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Antipyretics

Analgesics

Antirheumatic Agents

Anti-Allergic Agents

Central Nervous System Depressants

Dermatologic Agents

Anti-Infective Agents

Antibodies

Dexamethasone

Acetaminophen

Ibuprofen

Dexamethasone acetate

BB 1101

Antibodies, Bispecific

Immunoglobulins

Diphenhydramine

Promethazine

Ichthammol

Ranitidine

Ranitidine bismuth citrate

Immunoglobulins, Intravenous

Immunologic Factors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme 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

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Leukemia, Biphenotypic, Acute

Leukemia, Myelomonocytic, Acute

Precancerous Conditions

Myelodysplastic-Myeloproliferative Diseases

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Leukemia of Ambiguous Lineage

Myelodysplastic/myeloproliferative Disease

Venetoclax

Azacitidine

Decitabine

Antimetabolites

Participants receive decitabine IV over 1 hour on days 1-10 and may also receive decitabine on days 1-5 after achieving complete remission/complete remission with incomplete count recovery during consolidation/maintenance. Participants also receive venetoclax PO daily on days 1-28 of cycle 1 and on days 1-21 of subsequent cycles. Treatment repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Abhishek Maiti, MBBS

This phase II trial studies how well venetoclax and decitabine work in treating participants with acute myeloid leukemia that has come back or does not respond to treatment, or with high-risk myelodysplastic syndrome that has come back. Drugs used in chemotherapy, such as venetoclax and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

PRIMARY OBJECTIVE:

I. To determine the overall response rate (ORR) of venetoclax in combination with 10-day decitabine in patients with refractory/relapsed acute myeloid leukemia (AML); elderly (\> 60 year old) patients with newly diagnosed AML not eligible for intensive chemotherapy; patients with high-risk myelodysplastic syndrome (MDS) with bone marrow blasts between 10% and 20%, relapsed or refractory to prior hypomethylating agent (HMA) therapy, or chronic myelomonocytic leukemia (CMML) with bone marrow blasts \>= 10% regardless of prior therapy; AML patients with prior history of MDS or CMML who received therapy for the MDS or CMML and progressed to AML, and younger patients with newly diagnosed AML with poor risk complex karyotype and/or TP53 deletions/mutations and patients with blastic plasmacytoid dentritic cell neoplasm (BPDCN).

SECONDARY OBJECTIVES:

I. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination.

II. To determine the number of patients who achieve a hematologic improvement (HI) in platelets, hemoglobin, or absolute neutrophil count (ANC) and the number of patients who achieve \> 50% reduction in blasts on therapy with venetoclax/10-day decitabine.

III. To determine the safety of venetoclax in combination with 10-day decitabine in patients with refractory/relapsed AML.

IV. To determine the number of patients who transition towards stem cell transplantation upon achieving response with the combination venetoclax/10-day decitabine regimen.

V. To determine the incidence of infectious complications per cycle with venetoclax in combination with 10-day decitabine.

EXPLORATORY OBJECTIVES:

I. To investigate possible relationships between baseline protein and gene expression signatures/mutation profile and BH3 profiling in predicting clinical response to the combination.

II. To characterize the pharmacokinetic (PK) profiles of venetoclax in combination with decitabine and antifungals in plasma samples.

OUTLINE:

Participants receive decitabine intravenously (IV) over 1 hour on days 1-10 and may also receive decitabine on days 1-5 after achieving complete remission/complete remission with incomplete count recovery during consolidation/maintenance. Participants also receive venetoclax orally (PO) daily on days 1-28 of cycle 1 and on days 1-21 of subsequent cycles. Treatment repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 3 to 6 months for up to 5 years.

Venetoclax and Decitabine in Treating Participants With Relapsed/Refractory Acute Myeloid Leukemia or Relapsed High-Risk Myelodysplastic Syndrome

A Phase II Study of Venetoclax in Combination With 10-Day Decitabine in Newly Diagnosed Elderly or Relapsed/Refractory Acute Myeloid Leukemia and Relapsed High-Risk Myelodysplastic Syndrome and Blastic Plasmacytoid Dendritic Cell Neoplasm

Baseline protein, gene expression signatures/mutation profile and BH3 profiling will be summarized with descriptive statistics. The correlation with endpoints of anti tumor activity will be explored where possible.

Will be defined as the proportion of patients who had CR (complete remission), CRp (complete remission with incomplete platelet recovery), CRi (complete remission with incomplete count recovery), PR (partial response) or marrow clearance of blasts within 3 months of treatment initiation among adult patients with acute myeloid leukemia (AML); and complete remission (CR), partial remission (PR) or marrow CR (mCR) lasting at least 4 weeks for patients with myelodysplastic syndrome (MDS). Descriptive statistics including plots, mean, median and standard deviations will be used to summarize data. Will estimate the ORR for the combination treatment, along with the 95% confidence interval. The association between ORR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.

Toxicity type, severity and attribution will be summarized for each patient using frequency tables.

Will be estimated using the method of Kaplan-Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log rank tests.

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
Venetoclax and Decitabine in Treating Participants With Relapsed/Refractory Acute Myeloid Leukemia or Relapsed High-Risk Myelodysplastic Syndrome	NCT03404193	Acute Myeloid L... Acute Myeloid L... Blastic Plasmac... Chronic Myelomo... Mixed Phenotype... Myelodysplastic... Recurrent Acute... Recurrent Acute... Recurrent Blast... Recurrent Chron... Recurrent Mixed... Refractory Acut... Refractory Blas... Refractory Chro... Refractory Mixe...	Decitabine Laboratory Biom... Venetoclax	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for refractory blastic plasmacytoid dendritic cell neoplasm