Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

IDH305 + Standard of care for patients that are medically fit for induction.

IDH305 + Standard of care for patients that are medically unfit for induction.

IDH305

Novartis Pharmaceuticals

The purpose of this study is to evaluate the safety, tolerability and potential efficacy of IDH305 with standard treatments for newly diagnosed IDH1R132 mutant acute myeloid leukemia (AML).

A Dose Finding Study of IDH305 With Standard of Care in IDH1 Mutant Acute Myeloid Leukemia

A Phase I, Open Label, Multicenter, Dose Finding Study of IDH305 With Standard of Care in IDH1 Mutant Acute Myeloid Leukemia

To characterize the PK profile of IDH305 with SOC medications (each Arm)

To characterize preliminary anti-tumor activity for each arm of the study. (Arm 1 and Arm 2)

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Neoadjuvant administration of IDH305 at 550 mg BID for 6 weeks followed by surgical resection at 6 weeks. If there is no evidence of progressive disease at 6 weeks (clinical, radiographic or histopathologic exam), the patient will continue on IDH305 at 550 mg BID post-operatively for a maximum of 11 additional 28 day cycles. Subsequent assessment of disease will occur every 2 months starting in Cycle 2.

Patients who have inoperable tumors but measurable 2HG pre-treatment will be treated with IDH305 at 550 mg BID x 6 weeks. If there is adequate sustained knockdown of 2HG on MRS and disease is stable or improved, then the patient will continue on treatment for a maximum of 11 additional 28 day cycles.

Cohort A - neoadjuvant administration of IDH305 at 550 mg BID for 6 weeks followed by surgical resection at 6 weeks. If there is no evidence of progressive disease at 6 weeks (clinical, radiographic or histopathologic exam), the patient will continue on IDH305 at 550 mg BID post-operatively for a maximum of 11 additional 28 day cycles. Subsequent assessment of disease will occur every 2 months starting in Cycle 2.

Cohort B - patients who have inoperable tumors but measurable 2HG pre-treatment will be treated with IDH305 at 550 mg BID x 6 weeks. If there is adequate sustained knockdown of 2HG on MRS and disease is stable or improved, then the patient will continue on treatment for a maximum of 11 additional 28 day cycles.

IDH1 mutations are thought to be among the earliest mutations occurring during transformation of glial cells into gliomas and dependence on the IDH-2HG pathway for survival and growth may be most relevant during the indolent phase of low grade tumor growth. However, the preclinical workup of IDH inhibitors was technically unable to assess low grade gliomas because the cells do not grow in vitro and so cannot be cultured, and the cells have such a low proliferation rate that they do not grow in mouse in vivo models. Despite this, Dr. Maher and colleagues have studied low grade metabolism in low grade gliomas in vivo, in patients undergoing surgical resection and infused with 13C-glucose or 13C-acetate. 13C-labeled tumor can be studied by 13C-nuclear magnetic resonance (NMR) ex vivo. 13C-NMR data from IDH-mutated low grade gliomas demonstrate that these tumors are highly metabolically active, capable of oxidizing both glucose and acetate while these substrates also contribute carbon to actively making 2HG (manuscript in preparation). These data strongly suggest that the low grade tumors may be dependent on the IDH pathway for maintaining the altered metabolic state of the cell and altered epigenome necessary for tumor growth. Treating low grade gliomas during the period of indolent growth poses a challenge in terms of evaluating a molecular targeted therapy for response and survival. Standard MRI assessment for low grade gliomas based on T2/FLAIR signal can be difficult to quantitate and reflects additional non-specific changes in the tumor microenvironment including edema and reactive gliosis. This is exacerbated by the natural history of these tumors for which there may be no change in tumor size over years. Added to this is the uncertainty that a drug was able to penetrate the blood brain barrier, enter the tumor and inhibit the target. To date, there is no non-invasive way to determine target inhibition, leaving the patients on a drug that may not inhibit the target and the investigator unsure if data being obtained reflects true activity. The current clinical trial addresses these challenges through a neoadjuvant clinical trial that combines non-invasive evaluation of 2HG by MRS to assess target inhibition within 1 week of study entry and direct tumor tissue analysis after 6 weeks on study in the surgical cohort. The comprehensive planned tissue analysis is designed to assess the impact of IDH305 on metabolic pathways, the epigenome and transcriptome, in addition to standard assessment of cellular proliferation and cell kill. A second cohort of patients, the non-surgical cohort, will include patients with a presumptive diagnosis of IDH-mutated glioma based on elevated 2HG on screening 2HG MRS but without a surgical resection planned because of perceived high risk of the procedure. It is anticipated that \~ 93% of these patients will have an IDH1 mutation and thus treatment with the IDH1 selective inhibitor will knockdown 2HG. For patients with an IDH2 mutation (\~7-8%), we anticipate that there will be no change in 2HG. These patients will come off study, sparing them any potential toxicity without potential benefit.

Phase 2 Study of IDH305 in Low Grade Gliomas

A Phase 2 Study of the IDH1 Inhibitor, IDH305, for the Treatment of IDH1 Mutated Low Grade Glioma Patients Who Have Measurable 2HG by MR Spectroscopy

Number of participants treated with IDH305 leads to sustained knockdown of 2HG by MR spectroscopy from Baseline.

Number of participants with radiographic and clinical response to knockdown of 2HG by IDH305 compared to Baseline.

University of Texas Southwestern Medical Center

Cholangiocarcinoma

Glioblastoma

Preleukemia

Myelodysplastic Syndromes

Astrocytoma

Oligodendroglioma

Bile Duct Cancer

A Phase I study of IDH305 in patients with advanced malignancies that harbor IDH1R132 mutations.

A Study of IDH305 in Patients With Advanced Malignancies That Harbor IDH1R132 Mutations

A Phase I Study of IDH305 in Patients With Advanced Malignancies That Harbor IDH1R132 Mutations

To estimate the maximum tolerated dose/recommended dose for expansion (MTD/RDE)

To characterize the safety and tolerability of IDH305

To assess any preliminary anti-tumor activity of IDH305

Oligoastrocytoma

study drug used to inhibit IDH1 mutation in these tumors, resulting in anti-tumor activity.

Andrew S Chi, MD, PhD

The purpose of this study is to found out if the drug IDH305 is safe and effective in subjects with IDH1 mutant grade II or III glioma that has progressed after observation or radiation therapy.

IDH305 is an orally available, brain-penetrant, mutant-selective allosteric IDH1 inhibitor that blocks mutant IDH1-dependent production of 2-HG.

Trial of IDH305 in IDH1 Mutant Grade II or III Glioma

Phase 2 Study of IDH305 in Subjects With IDH1 Mutant Grade II or III Glioma That Has Progressed After Observation or Radiation Therapy

The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) 4.03

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Dose Finding Study of IDH305 With Standard of Care in IDH1 Mutant Acute Myeloid Leukemia	NCT02826642	Acute Myeloid L...	IDH305	18 Years -	Novartis
Phase 2 Study of IDH305 in Low Grade Gliomas	NCT02987010	Glioma	IDH305	18 Years -	University of Texas Southwestern Medical Center
Phase 2 Study of IDH305 in Low Grade Gliomas	NCT02987010	Glioma	IDH305	18 Years -	University of Texas Southwestern Medical Center
A Study of IDH305 in Patients With Advanced Malignancies That Harbor IDH1R132 Mutations	NCT02381886	Advanced Malign...	IDH305	18 Years -	Novartis
A Dose Finding Study of IDH305 With Standard of Care in IDH1 Mutant Acute Myeloid Leukemia	NCT02826642	Acute Myeloid L...	IDH305	18 Years -	Novartis
A Study of IDH305 in Patients With Advanced Malignancies That Harbor IDH1R132 Mutations	NCT02381886	Advanced Malign...	IDH305	18 Years -	Novartis
Trial of IDH305 in IDH1 Mutant Grade II or III Glioma	NCT02977689	Glioma	IDH305	18 Years -	NYU Langone Health
Trial of IDH305 in IDH1 Mutant Grade II or III Glioma	NCT02977689	Glioma	IDH305	18 Years -	NYU Langone Health

Spots Global Cancer Trial Database for idh305

Every month we try and update this database with for idh305 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 idh305

Every month we try and update this database with for idh305 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 idh305 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.