Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Dose-escalation, LGH447 in combinatinon with BYL719

LGH447 + BYL719 (dosing according to MTD/RP2D from Phase Ib portion of the study)

LGH447 alone (dosing according to single-agent RDE)

LGH447

BYL719

Novartis Pharmaceuticals

This is a Phase Ib/II study with the primary purpose of the Phase Ib part being to estimate the MTD and/or recommended phase 2 dose (RP2D) of the combination of LGH447 and BYL719 when administered orally to adult patients with relapsed and refractory multiple myeloma. Once the MTD and/or RP2D is determined for the combination of LGH447 and BYL719, additional patients will be enrolled in the Phase II part to determine whether the combination of LGH447 and BYL719 exhibits improved anti-multiple myeloma activity compared to single agent LGH447. This trial never made it to the Phase II part of the this trial.

Study of the Safety and Effectiveness of LGH447 and BYL719 in Patients With Relapsed and Refractory Multiple Myeloma

A Phase Ib/II, Multi-center, Study of Oral LGH447 in Combination With Oral BYL719 in Patients With Relapsed and Refractory Multiple Myeloma

Using a Bayesian logistic regression model (BLRM) to guide dose escalation and predict MTD or determine the RP2D for LGH447 in combination with BYL719 in relapsed and refractory multiple myeloma. The frequency and characteristics of DLTs will be assessed.

The proportion of patients with a confirmed best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as assessed by Investigators using the International Myeloma Working group (IMWG) Criteria with modifications.

End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.

The ORR percent change between the two arms, LGH447 in combination with BYL719 and LGH447 alone, is the parameter of interest. Both observed and Bayesian estimates of ORR percent change along with 80% confidence intervals and credible intervals will be calculated. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.

Assessments consisted of recording all adverse events (AEs) and serious adverse events (SAEs), the regular monitoring of hematology, blood chemistry, urinalysis, and coagulation parameters, as well as electrocardiograms.

To determine the single and multiple dose PK profiles of the LGH447 and BYL719 combination (Phase Ib and II) and LGH447 alone (Phase II), by measuring plasma concentrations of LGH447 and BYL719 respectively at different timepoints prior and post study drug combination dosing on several days within cycle 1 and subsequent cycles for all patients in the Phase 1b and for the first 15 patients in each arm in the Phase 2 portion of the study. PK parameters including but not limited to Cmax, AUCinf, AUClast, AUCtau,T1/2, Tmax, Racc, CL/F, and Vz/F

Cycle 2 = 28 days; LGH447-mediated target modulation of the PIM pathway will be assessed from the collection of bone marrow biopsy and/or aspirates by flow cytometry, immunohistochemistry, or other methods as deemed appropriate. Decreases in the phosphorylation of markers (eg. S6RP and 4EBP1) will be measured in both pre- and post-dose bone marrow aspirate samples and peripheral blood samples.

Both observed and Bayesian estimates of absolute difference in ORR between the two arms will be calculated. The 80% confidence intervals and credible intervals for the difference will be provided. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.

Proportion of patients with a best overall response of sCR, CR, VGPR, PR, MR, or SD, using International Myeloma Working Group Criteria with modification. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.

Defined as the time from start of treatment to the date of event defined as the first documented PD/relapse, or death due to any cause, whichever comes first. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.

The time between date of randomization until first documented best overall response (sCR, CR, VPGR or PR). End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.

Defined as the duration from the first documented onset of PR or better response to the date of documented PD/relapse or death due to multiple myeloma. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.

Hematologic Neoplasms

This is a multi-center, open-label, dose escalation, Phase 1 study of oral LGH447 in Japanese patients with relapsed and/or refractory multiple myeloma for which no standard effective treatment options exist.

The study consists of a dose escalation part to estimate the maximum tolerated dose and/or the recommended dose for expansion and a dose expansion part to further assess safety and preliminary anti-cancer activity of LGH447 at the maximum tolerated dose and/or the recommended dose for expansion.

Dose Escalation Study of LGH447 in Japanese Patients With Relapsed and/or Refractory Hematologic Malignancies

A Multi-center, Open-label, Dose Escalation, Phase 1 Study of Oral LGH447 in Japanese Patients With Relapsed and/or Refractory Hematologic Malignancies

Estimate the maximum tolerated dose and/or recommended dose for expansion of LGH447 in Japanese patients

Adverse events, serious adverse events, changes in laboratory values, and electrocardiograms

PK parameters such as AUC, Cmax, Tmax, T1/2. Cycle = 28 days

Describe any preliminary anti-cancer activity associated with LGH447 based on International Myeloma Working group Criteria with modification.

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Midazolam

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Eligible patients will be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity.

Eligible patients will receive midazolam on two separate days, the first dose will be administered prior to the start of LGH447 and the second will be co-administered with LGH447. After that, the patients will continue to be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity.

midazolam

The primary purpose of this dose escalation study is to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LGH447 as a single agent when administered orally once daily to adult patients with Multiple Myeloma (MM).

A Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma

A Multi-Center, Open-Label, Dose Escalation, Phase 1 Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma

Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

Summary of PK parameters such as AUC, Cmax,

Changes between pre and post treatment levels in bone marrow aspirates and whole blood.

Overall Response Rate (ORR), Duration of Response (DOR), and Progression Free Survival (PFS) based on International Myeloma Working Group Response Criteria.

PK parameters of midazolam and 1-hydroxymidazolam, such as AUC and Cmax, as well as metabolic ratio of midazolam.

Symptoms and General Pathology

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

Midostaurin

Protein Kinase Inhibitors

Enzyme Inhibitors

LGH447 monotherapy in patients with AML or MDS

LGH447 + midostaurin in patients with AML

LGH447 + midostaurin

This study will assess the safety and preliminary efficacy of escalating doses of LGH447 monotherapy in AML and MDS and LGH447 in combination with midostaurin in AML.

A Safety and Efficacy Study of LGH447 in Patients With Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)

A Phase I, Multicenter, Open-label Study of Oral LGH447 in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Frequency and characteristics of dose limiting toxicities

Includes changes in hematology and blood chemistry values, assessments of physical examinations, vital signs, and electrocardiograms (ECGs)

LGH447 and midostaurin plasma concentrations and basic PK parameters

To assess any preliminary anti-tumor activity in AML or high risk MDS associated with LGH447

To assess any preliminary anti-tumor activity in AML or high risk MDS associated with LGH447 in combination with midostaurin

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of the Safety and Effectiveness of LGH447 and BYL719 in Patients With Relapsed and Refractory Multiple Myeloma	NCT02144038	Relapsed and Re...	LGH447 BYL719	18 Years -	Novartis
Dose Escalation Study of LGH447 in Japanese Patients With Relapsed and/or Refractory Hematologic Malignancies	NCT02160951	Multiple Myelom...	LGH447	18 Years -	Novartis
A Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma	NCT01456689	Multiple Myelom...	LGH447 midazolam	18 Years -	Novartis
A Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma	NCT01456689	Multiple Myelom...	LGH447 midazolam	18 Years -	Novartis
Study of the Safety and Effectiveness of LGH447 and BYL719 in Patients With Relapsed and Refractory Multiple Myeloma	NCT02144038	Relapsed and Re...	LGH447 BYL719	18 Years -	Novartis
A Safety and Efficacy Study of LGH447 in Patients With Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)	NCT02078609	AML and High Ri...	LGH447 LGH447 + midost...	18 Years -	Novartis

Spots Global Cancer Trial Database for lgh447

Every month we try and update this database with for lgh447 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 lgh447

Every month we try and update this database with for lgh447 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 lgh447 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.