Neoplasms

Nervous System Diseases

Immune System Diseases

All Conditions

Musculoskeletal Diseases

Symptoms and General Pathology

Rare Diseases

Myasthenia Gravis

Muscle Weakness

Paresis

Asthenia

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Mycophenolic Acid

Azathioprine

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Enzyme Inhibitors

MA group: 1 tablet AZA placebo and 4 tablets MA (180mg/tab,720 mg/day) twice daily

AZA group: 1 tablet AZA (50mg/tab) and 4 tablets MA placebo twice daily

Mycophenolic acid

1 tablet AZA (50 mg/tab) and 4 tablets MA placebo twice daily

Jiann-Horng Yeh, M.D.

This is an randomized, double-blind, double-dummy trial, and the objective is to compare the efficacy and safety of Mycophenolic acid (MA) and Azathioprine (AZA), immunosuppressive drugs, in myasthenia gravis patients. This prospective study will enroll 40 myasthenia gravis (MG) patients who are poor controlled under prior steroid therapy. All subjects should be randomly assigned to MA group and AZA group that will receive routine pyridostigmine and prednisolone in combination with MA or AZA.

This will be a double-dummy study to keep the blinded quality.

* MA group: 1 tablet AZA placebo and 4 tables MA (180 mg/tab,720 mg/day) twice daily.
* AZA group: 1 tablet AZA (50mg/tab) and 4 tables MA placebo twice daily.

  * When patients achieve minimal manifestation (MM, i.e. complete remission), which lead to normal daily routine, the dose of pyridostigmine should reduce to 240 mg/day (4 tablets) or less. The dose of steroid should be stepped down by 10 mg qod (every other day) for every 2 weeks until the dose achieves 40 mg qod. After that, the dose should be stepped down by 5 mg qod for every month.
  * When disease progresses and is no longer maintaining minimal manifestation, the dose of steroid will be stepped up by 10 mg qod for every 2 weeks until achieve clinical stable remission. The taper rule of steroid could start again 1 month after stabilization.
  * Every patient will be treated for 1 year. If the patient could not achieve MM within 1 year, the blind of individual patient will be opened and the patients will be crossed over to another medical treatment. The efficacy and safety of second medication will be observed openly until the end of study.
  * When the muscle weakness worsens under established study schedule, plasmapheresis could be conducted to improve the condition rapidly.

Trial of Mycophenolic Acid Versus Azathioprine in the Treatment of Corticosteroid-refractory Myasthenia Gravis

Randomized, Double-blind, Double-dummy Trial of Mycophenolic Acid Versus Azathioprine in the Treatment of Corticosteroid-refractory Myasthenia Gravis

Qualitix Clinical Research Co., Ltd.

Jiann-Horng Yeh / M.D.

Blood and Lymph Conditions

Leukemia

Preleukemia

Myelodysplastic Syndromes

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Azacitidine

Decitabine

Antimetabolites

Patients randomized to receive Decitabine 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.

Patients randomized to receive Azacitidine 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.

20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.

75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.

Elias Jabbour, MD

The goal of this clinical research study is to compare how two different drugs, decitabine and azacitidine, when given on a shorter than standard dosing schedule can help to control MDS. The safety of the drugs will also be studied.

Decitabine is designed to damage the DNA (the genetic material) of cells, which may cause cancer cells to die.

Azacitidine is designed to block certain proteins in cancer cells whose job is to stop the function of the tumor-fighting proteins. By blocking the "bad" proteins, the tumor-fighting genes may be able to work better. This could cause the cancer cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups:

* If you are in Group 1, you will receive decitabine by vein over about 1 hour.
* If you are in Group 2, you will receive azacitidine either as an injection under your skin or through a vein. If by vein, the infusion will take about an hour.

At first, there will be an equal chance of being assigned to either group. However, as the study goes on and more information becomes available, the chance of being assigned to the group that has shown the most effectiveness will increase. However, once you are already enrolled and assigned to a group, you will not be eligible to change groups.

Study Drug Administration:

Each cycle is 28 days.

You will receive the study drug on Days 1-3 of every cycle and you will receive at least 2 cycles of study drug.

Study Visits:

Every 7-14 days, blood (about 2 tablespoons) will be drawn for routine tests.

At the end of Cycle 2, you will have a bone marrow biopsy and/or aspirate to check the status of the disease. This will then be repeated every 2-4 cycles until any point that the disease appears to have responded to the study drug, then as often as the study doctor thinks is necessary. To collect a bone marrow biopsy/aspirate, an area of the hip bone is numbed with anesthetic, and a small amount of bone and/or bone marrow is withdrawn through a large needle.

After Cycle 3:

If the study doctor decides it is acceptable, you may be allowed to receive treatment from your local cancer doctor. However, you have to return to Houston at least every 3 months for your study visits.

The frequency of the visits will depend on what the doctor thinks is in your best interest.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Follow-Up Visits:

One (1) time every 3 months after your last dose of study drug, you will return to the clinic for a bone marrow aspiration to check the status of the disease.

Other Information:

You may be given other drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.

This is an investigational study. Decitabine and Azacitidine are both FDA approved and commercially available for use in patients with MDS.

Up to 120 patients will take part in this study. All will be enrolled at MD Anderson.

Decitabine Versus Azacitidine in Myelodysplastic Syndrome Patients With Low and Intermediate-1 Risk

Phase II Randomized Study of Lower Doses of Decitabine (DAC; 20 mg/m2 IV Daily for 3 Days Every Month) Versus Azacitidine (AZA; 75 mg/m2 SC/IV Daily for 3 Days Every Month) in Myelodysplastic Syndrome (MDS) Patients With Low and Intermediate-1 Risk Disease

Overall Response = complete remission (CR) + partial remission (PR) + marrow CR (mCR) + hematologic improvement (HI). CR is normalization of peripheral blood and bone marrow with \<5% bone marrow blasts, a peripheral blood granulocyte count \> (1.0 x 10\^9/L, and platelet count \> 100 x 10\^9/L). PR is same as CR except for the presence of 6-15% marrow blasts, or 50% reduction if \<15% at start of treatment. Marrow CR is blasts \</= 5% and decreased by \>/=50% from baseline. HI is platelets increase by 50% and to above 30 x 10\^9/L untransfused (if lower than that pre-therapy; or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by \> 50%; or monocytosis reduction by \> 50% if pretreatment \> 5 X1 0\^9/L.

Participants who were transfusion dependent at baseline prior to starting therapy on the Decitabine or Azacitidine arm will be analyzed for transfusion independence. Transfusion independence defined as being transfusion-free for ≥8 consecutive weeks between the first dose and study treatment discontinuation.

M.D. Anderson Cancer Center

Patients randomized to receive Decitabine 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.

Decitabine: 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.

Patients randomized to receive Azacitidine 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.

Azacitidine: 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Elias Joseph MD./Professor

Participants With a Response

Participants analyzed for Transfusion Independence must have been transfusion dependent at baseline. Thirty-seven participants in the Decitabine arm and nineteen participants in the Azacitidine arm where transfusion dependent prior to treatment on this study.

Number of Participants Who Became Transfusion Independent

Overall Study

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Neoplasms by Histologic Type

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Chronic Graft Versus Host Disease

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Venetoclax

Participants will receive JNJ-74856665 orally in a 21-day cycle. The dose levels will be escalated based on the decisions of the Study Evaluation Team (SET) until a recommended Phase 2 dose (RP2D) has been identified.

Participants will receive JNJ-74856665 orally in combination with AZA administered intravenously (IV) or subcutaneously (SC) in a 28-day cycle.

Participants will receive JNJ-74856665 orally in combination with VEN in a 28-day cycle.

Participants will receive JNJ-74856665 orally in a 21-day cycle. Participants with transfusion dependent relapsed/refractory Myelodysplastic Syndrome (MDS) will be included.

JNJ-74856665 will be administered orally.

JNJ-74856665

AZA will be administered IV infusion or SC injection.

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to determine the safety, tolerability, maximum tolerated doses (MTDs) and recommended Phase 2 doses (RP2Ds) of JNJ-74856665 as monotherapy and/or in combinations.

This is first-in-human (FIH) Phase 1, dose escalation study of JNJ-74856665 alone or in combination with Azacitidine or Venetoclax in participants with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS). Participants with Chronic Myelomonocytic Leukemia (CMML) are also eligible and will either receive JNJ-74856665 as monotherapy or in combination with Azacitidine. AML is a heterogeneous disease characterized by uncontrolled clonal expansion of hematopoietic progenitor cells (myeloid blasts) in the peripheral blood, bone marrow, and other tissues and is the second most common form of leukemia. MDS are a heterogeneous group of malignant hematopoietic stem cell disorders that are characterized by cytopenias, myeloid dysplasia, and a risk of transformation to AML. JNJ-74856665 is an orally bioavailable, potent, and selective dihydroorotate dehydrogenase (DHODH) inhibitor that binds to the enzyme's ubiquinone binding site promoting AML/MDS differentiation as well as cell cycle arrest and apoptosis. Azacitidine (5-azacytidine) is a nucleoside metabolic inhibitor that has been US Food and Drug Administration-approved for several MDS subtypes. Venetoclax (VEN) is a BCL-2 inhibitor that can restore activation of apoptosis in malignant cells, the survival of which often depends on dysregulation of this pathway. The study is divided into 3 periods: a Screening Phase (within 28 days before the first dose of study drug), a Treatment Phase (first dose of study drug until the completion of the end-of-treatment visit) and a Post-treatment Follow-up Phase (up to the end of study participation or end of study). The end of study is defined as the last study assessment for the last participant in the study. Total duration of study is up to 2 years and 10 months. Efficacy, safety, pharmacokinetics (PK), and biomarkers will be assessed at specified time points during this study. Participants safety and study conduct will be monitored throughout the study.

A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

A Phase 1, FIH, Dose Escalation Study of JNJ-74856665 (Dihydroorotate Dehydrogenase [DHODH] Inhibitor) Alone or in Combination in Participants With AML or MDS

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinicaltrials/ transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Number of participants with AEs by severity will be reported as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

Plasma samples will be analyzed to determine concentrations of JNJ-74856665.

Biomarker levels of intermediates including DHO, orotate, and uridine will be measured by liquid chromatography/mass spectrometry (LC-MS) for JNJ-74856665.

Clinical response will be assessed per the modified European Leukemia Net (ELN) 2017 recommendations.

Clinical response will be assessed per the modified International Working Group 2018 response criteria.

Overall improvement rate is defined as the percentage of participants achieving complete remission, partial remission, or hematologic improvement (HI) according to modified International Working Group (IWG) response criteria.

TTR defined for the responders as the time from the date of first dose of study treatment to the date of initial documentation of a first response as defined in the disease-specific response criteria.

DOR will be calculated from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first. For participants with disease that has not relapsed and who are alive, data will be censored at the last disease evaluation before the start of any subsequent anticancer therapy.

TI is defined as the absence of RBC and platelet transfusions for 8 weeks or longer after starting study treatment for participants with a primary diagnosis of AML or CMML-2, and 16 weeks or longer for participants with a primary diagnosis of MDS.

Janssen Research & Development, LLC

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Neoplasm Metastasis

Melanoma

Carcinoma, Renal Cell

Sarcoma

Neoplasms, Germ Cell and Embryonal

Lung Neoplasms

Neoplastic Processes

Neoplasms, Connective and Soft Tissue

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Soft Tissue Sarcoma

Germ Cells Tumors

Azacytidine (aerosolized) at escalating doses (given on 3 consecutive days in the first week of every 3-week cycle) with a flat dose of Bintrafusp alfa 2400 mg (given on day 13 \[+/- 3 days\] of every 3-week cycle starting with Cycle 2)

Azacytidine (aerosolized) at the RP2D established in Phase I (given on 3 consecutive days in the first week of every 3-week cycle) with a flat dose of Bintrafusp alfa 2400 mg (given on day 13 \[+/- 3 days\] of every 3-week cycle)

Patients will receive AZA via commercial device, AeroEclipse II Breath Actuated Nebulizer.

AeroEclipse II Breath Actuated Nebulizer

Bintrafusp alfa will be administered on Day 13 (+/- 3 days) of every 3-week cycle (i.e., Q3W \[once every 3 weeks\]) at a fixed intravenous dose of 2400 mg; Bintrafusp alfa does not start until cycle 2 of the phase I portion.

Bintrafusp alfa

Patients will receive azacytidine (aersolized; via commercial AeroEclipse II Breath Actuated Nebulizer device) on 3 consecutive days in the first week of every 3-week cycle. Phase I: Azacytidine will be given at escalating doses. Phase II: Azacytidine will be given at the RP2D established in Phase I.

Azacytidine

David S Schrump, M.D.

Background:

About one-third to one-half of all people dying of extrathoracic malignant diseases have cancer that has spread to the lungs. Surgery may help some people. But most people with pulmonary metastases do not survive long. Researchers want to see if a combination of drugs can help.

Objective:

To find a safe dose of Azacytidine, when taken as a fine mist that is inhaled (aerosolized Azacytidine), together with Bintrafusp Alfa to treat cancers that have spread to the lungs.

Eligibility:

Adults ages 18 and older who have cancer that has spread to the lungs, cannot be cured with surgery, and has not responded to standard treatments.

Design:

Participants will get Azacytidine by breathing treatments once a day for 3 days each week, for 3 weeks. The 3-week period is 1 cycle. Each course of treatment is 3 cycles.

Once per cycle, participants will get Bintrafusp Alfa via IV. An IV is a small tube that is put into an arm vein.

Participants will keep a diary of any side effects.

Participants can take the study drugs for as long as they can continue treatment.

Participants will have medical histories and physical exams. They will give blood, urine, and lung lining fluid samples. Tumor samples will be taken via bronchoscopy. They will have lung function tests.

Participants will have an imaging scan that shows how spray particles move in their airway when they inhale. They will have tumor imaging scans of the chest and brain.

Participants will have a follow-up visit 30 days after they stop treatment....

Background:

While malignancies of diverse histologies express a variety of cancer-testis antigens (CTAs), immune responses to these proteins appear uncommon in cancer patients due to low-level, heterogeneous antigen expression, as well as local and systemic immunosuppression.

CTAs such as NY-ESO-1 and MAGE-A3 can be up-regulated in tumor cells of various histologies, but not in normal cells, by DNA demethylating agents such as decitabine (DAC) and azacytidine (AZA). Up-regulation of these CTAs facilitates CTL-mediated lysis of tumor cells.

Clinical trials have demonstrated impressive regressions of tumors expressing NY-ESO-1 following adoptive immunotherapy targeting this CTA.

In addition to shared CTAs, unique neoantigens are major targets for immune eradication of cancer cells.

DNA demethylating agents not only up-regulate cancer-testis (CT) genes but also induce expression of endogenous retroviruses (ERV) which further augments immunogenicity of cancer cells.

Additionally, DNA demethylating agents enhance antigen processing and presentation by cancer cells, and inhibit activity of myeloid derived suppressor cells (MDSC), thereby increasing the efficacy of immune checkpoint inhibitors in murine tumor models.

Despite these provocative preclinical results, epigenetic priming for immune checkpoint blockade has yet to be translated to humans due to systemic toxicities and pharmacokinetic/pharmacodynamic limitations that prevent optimal dosing of DNA demethylating agents.

One potential strategy to enhance delivery of DNA demethylating agents to pulmonary malignancies while minimizing systemic toxicities is to administer these drugs by inhalation techniques.

Preclinical studies have demonstrated that aerosolized AZA mediates epigenetic activation of gene expression in orthotopic lung cancers, and significantly prolongs survival of mice bearing these tumors without systemic toxicities.

Conceivably, inhaled AZA may help to prime pulmonary malignancies for immune checkpoint blockade.

In this study, the optimal dose of inhaled AZA will be established in patients with unresectable pulmonary metastases who are receiving the dual immune checkpoint inhibitor-TGF-Beta trap, Bintrafusp alfa (M7824).

This trial is intended to establish the rationale for further evaluation of inhalational epigenetic priming regimens in combination with immune checkpoint inhibitors or adoptive cell transfer regimens in patients with locally advanced pulmonary malignancies.

Objectives:

Phase I component: To determine pharmacokinetics, toxicities, maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of aerosolized AZA in patients receiving Bintrafusp alfa for unresectable pulmonary metastases

Phase II component: To determine frequency of intrathoracic clinical responses in these patients following administration of aerosolized AZA at the RP2D and Bintrafusp alfa.

Both components: To determine safety of aerosolized AZA and Bintrafusp alfa in patients with unresectable pulmonary metastases.

Eligibility Criteria:

Patients with histologically or cytologically proven, unresectable pulmonary metastases from sarcomas, melanomas, germ cell tumors, or epithelial malignancies (except lung or kidney cancers) who have received first line standard of care treatment for their metastatic disease.

Measurable disease by RECIST

Patients are eligible irrespective of intratumoral PD-L1 expression.

Patients with prior treatment with an immune checkpoint inhibitor and DNA demethylating agents may be eligible for study provided they did not experience serious immune adverse events that required discontinuation of the drug, and more than three weeks have elapsed since treatment

Patients greater than or equal to 18 years; ECOG performance status of 0-1 without evidence of unstable or decompensated myocardial disease; adequate pulmonary reserve evidenced by FEV1 greater than or equal to 60% predicted, FEV1/FVC ratio greater than or equal to 60%, and adjusted DLCO greater than or equal to 60% predicted; pCO2 less than or equal to 45 mm Hg and pO2 greater than or equal to 60 mm Hg on room air ABG

Adequate renal, hepatic and hematopoietic function

Design:

Subjects will receive aerosolized AZA on three consecutive days (i.e.; Days 1, 2, and 3, or Days 3, 4, 5) of a 21-day cycle. Three cycles constitute one course of treatment.

Bintrafusp alfa will be administered at a fixed dose of 2400 mg. During Phase I, Bintrafusp alfa will be administered on Day 13 (i.e., once every 3 weeks, one week after AZA) of each cycle starting from Cycle 2 of Course 1 (i.e., no Bintrafusp alfa in the first cycle of Course 1). During Phase II, Bintrafusp alfa will be administered the day after the last AZA treatment, during Week 1 of each treatment cycle.

The dose of AZA will be escalated during Phase I using a 3+3 design with no intrapatient dose escalation.

The dose of AZA will be sequentially increased to maximize intra-tumoral DNMT1 depletion while avoiding Grade 3 or greater pulmonary or systemic toxicities attributable to this agent during the first cycle of therapy.

Treatment evaluation will be three weeks +/- one week following completion of each course of therapy.

Once the RP2D of aerosolized AZA has been defined, that dose level will be expanded to a total of 9 patients to determine response rates at the RP2D using a Simon two stage design for Phase II trials.

Approximately 42 patients will be accrued to this trial.

Aerosolized Azacytidine as Epigenetic Priming for Bintrafusp Alfa-Mediated Immune Checkpoint Blockade in Patients With Unresectable Pulmonary Metastases From Sarcomas, Germ Cell Tumors, or Epithelial Malignancies

Phase I/II Evaluation of Aerosolized Azacytidine as Epigenetic Priming for Bintrafusp Alfa-Mediated Immune Checkpoint Blockade in Patients With Unresectable Pulmonary Metastases From Sarcomas, Germ Cell Tumors, or Epithelial Malignancies

DLTs at each Phase I dose level will be reported. Pharmacokinetic analysis will be conducted using non-compartmental methods. All patients will be evaluable for toxicity from the time of their first treatment with AZA/ Bintrafusp alfa. Dose limiting toxicities will be assessed during the first 3 cycles of AZA/ Bintrafusp alfa therapy. Patients who have measurable disease present at baseline, have received at least 9 weeks of AZA/Bintrafusp alfa therapy (three cycles), and have had their disease re-evaluated will be considered evaluable for response.

Patients who have measurable disease present at baseline, have received at least 9 weeks of AZA/Bintrafusp alfa therapy (three cycles), and have had their disease re-evaluated will be considered evaluable for response provided.

National Cancer Institute (NCI)

Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition.

Dose C: Single oral administration with two 150-mg tablets under fed condition.

300-mg (three 100-mg tablets) once daily for 21 days of a 28-day cycle.

oral azacitidine 300-mg once daily for 3 total doses with two 150-mg tablets (fasted and fed) or three 100-mg tablets (fasted).

oral azacitidine

Barry Skikne, M.D.

The primary purpose of this study is to evaluate the pharmacokinetics of oral azacitidine when administered once daily as two 150-mg tablets, including the effect of food, and to evaluate the bioavailability of oral azacitidine 300-mg when administered as two 150-mg tablets relative to three 100-mg tablets.

Study to Evaluate Pharmacokinetics, Food Effect, Safety and Efficacy of Oral Azacitidine

A PHASE 1, MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS AND EFFECT OF FOOD OF A NEW TABLET FORMULATION OF ORAL AZACITIDINE, AND TO EVALUATE THE SAFETY AND EFFICACY OF ORAL AZACITIDINE IN SUBJECTS WITH MYELODYSPLASTIC SYNDROMES, CHRONIC MYELOMONOCYTIC LEUKEMIA OR ACUTE MYELOID LEUKEMIA

PK-Area under the plasma concentration time curve (AUC)

Observed maximum concentration in plasma (Cmax)

PK-Time to maximum plasma concentration (Tmax)

To evaluate the effect of gastric acid pH modulation, through a proton pump inhibitor, on the PK of oral azacitidine.

Number of participants with adverse events

Proportion of subjects achieving hematological response/improvement

Proportion of subjects achieving RBC transfusion independence

Proportion of subjects achieving platelet transfusion independence

Celgene

Participants will receive venetoclax once daily (QD) (Days 1-14) in combination with AZA QD (7 days of the first 9 days) of each 28 day cycle.

Participants will receive placebo once daily (QD) (Days 1-14) in combination with AZA QD (7 days of the first 9 days) of each 28 day cycle.

Subcutaneous (SC) or Intravenous (IV) injection

Placebo

ABBVIE INC.

Myelodysplastic Syndrome (MDS) is a group of disorders that gradually affect the ability of a person's bone marrow (semi-liquid tissue present in many bones like backbones) to produce normal blood cells. Some people with MDS have a risk of the disease progressing to acute myeloid leukemia (AML), and a risk of death from the disease itself. Symptoms of MDS include fatigue, shortness of breath, unusual paleness due to anemia (low red blood cell count), easy or unusual bruising, and red spots just beneath the skin caused by bleeding. The purpose of this study is to see how safe and effective venetoclax and azacitidine (AZA) combination are when compared to AZA and a placebo (contains no medicine), in participants with newly diagnosed higher-risk MDS.

Venetoclax is an investigational drug being developed for the treatment of MDS. The study consists of two treatment arms - In one arm, participants will receive venetoclax and AZA. In another arm, participants will receive AZA and placebo. Adult participants with newly diagnosed higher-risk MDS will be enrolled. Around 500 participants will be enrolled in approximately 220 sites worldwide.

Participants in one arm will receive oral doses of venetoclax tablet and intravenous (infusion in the vein) or subcutaneous (given under the skin) AZA solution. Participants in another arm will receive oral doses of placebo tablet and intravenous or subcutaneous AZA solution.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.

Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Disease Activity In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome

A Randomized, Double-Blind, Phase 3 Study Evaluating the Safety and Efficacy of Venetoclax in Combination With Azacitidine in Patients Newly Diagnosed With Higher-Risk Myelodysplastic Syndrome (Higher-Risk MDS)

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

OS is defined as the number of days from the date of randomization to the date of death of any cause, or last known date to be alive.

mOR \[complete remission (CR) + marrow complete remission (mCR) + partial response (PR)\] is defined as achieving a CR, mCR, or PR at any time point during the study per the modified International Working Group (IWG) 2006 criteria for myelodysplastic syndrome (MDS).

Overall HI is defined as achieving the response of HI-platelet or HI-neutrophil, or HI-erythroid at any time point during the study prior to post-treatment therapy per the modified IWG 2006 criteria for MDS.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Mycophenolic Acid Versus Azathioprine in the Treatment of Corticosteroid-refractory Myasthenia Gravis	NCT00997412	Myasthenia Grav...	Mycophenolic ac... AZA	20 Years - 70 Years	Qualitix Clinical Research Co., Ltd.
Decitabine Versus Azacitidine in Myelodysplastic Syndrome Patients With Low and Intermediate-1 Risk	NCT01720225	Leukemia	Decitabine Azacitidine	18 Years -	M.D. Anderson Cancer Center
Decitabine Versus Azacitidine in Myelodysplastic Syndrome Patients With Low and Intermediate-1 Risk	NCT01720225	Leukemia	Decitabine Azacitidine	18 Years -	M.D. Anderson Cancer Center
A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)	NCT04609826	Acute Myeloid L... Myelodysplastic... Chronic Myelomo...	JNJ-74856665 AZA VEN	18 Years -	Janssen Research & Development, LLC
Aerosolized Azacytidine as Epigenetic Priming for Bintrafusp Alfa-Mediated Immune Checkpoint Blockade in Patients With Unresectable Pulmonary Metastases From Sarcomas, Germ Cell Tumors, or Epithelial Malignancies	NCT04648826	Sarcomas Melanomas Germ Cell Tumor... Epithelial Mali... Pulmonary Metas...	AeroEclipse II ... Bintrafusp alfa Azacytidine	18 Years -	National Institutes of Health Clinical Center (CC)
Study to Evaluate Pharmacokinetics, Food Effect, Safety and Efficacy of Oral Azacitidine	NCT01519011	Myelodysplastic... Leukemia, Myelo... Leukemia, Myelo...	oral azacitidin... oral azacitidin...	18 Years -	Celgene
Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Disease Activity In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome	NCT04401748	Myelodysplastic...	Venetoclax Azacitidine Placebo	18 Years -	AbbVie

Spots Global Cancer Trial Database for aza

Every month we try and update this database with for aza cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for aza

Every month we try and update this database with for aza cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for aza cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.