Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Clarithromycin

Rifampin

Ketoconazole

Ixazomib

Glycine

Anti-Bacterial Agents

Enzyme Inhibitors

Cytochrome P-450 CYP3A Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Antibiotics, Antitubercular

Antitubercular Agents

Clotrimazole

Miconazole

Antifungal Agents

Hormones

Hormone Antagonists

HIV Protease Inhibitors

Protease Inhibitors

Neurotransmitter Agents

Ixazomib 2.5 milligram (mg), capsule B, orally, once on Day 1 and 15 along with ketoconazole 400 mg, tablets, orally, once daily from Day 12 to 25 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Ixazomib 4 mg, capsule A, orally, once on Day 1 followed by ixazomib 4 mg, capsule B once on Day 15 of Cycle 1 (28-day treatment cycle) or ixazomib 4 mg, capsule B, orally, once on Day 1 followed by ixazomib 4 mg, capsule A once on Day 15 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Ixazomib 4 mg, capsule B, orally, under fasted state, once on Day 1 followed by ixazomib 4 mg, capsule B, orally, under fed state, once on Day 15 of Cycle 1 (28-day treatment cycle) or ixazomib 4 mg, capsule B, orally, under fed state, once on Day 1 followed by ixazomib 4 mg, capsule B, orally, under fasted state, once on Day 15 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Ixazomib, 4 mg, capsule B, orally, once on Day 8 along with rifampin 600 mg, capsule, orally, once daily from Day 1 to 14 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Ixazomib, 2.5 mg, capsule B, orally, once on Day 6 along with clarithromycin, 500 mg, tablet, orally, twice daily from Day 1 to 16 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Ixazomib 2.5 mg

Ixazomib 4 mg Capsule A

Ixazomib 4 mg Capsule B (Cycle 2 and beyond )

Ixazomib 4 mg Capsule B

Ketoconazole 400 mg tablets (Cycle 1 only)

Clarithromycin 500 mg tablets (Cycle 1 only)

Ixazomib 4 mg Capsule B (Cycle 1 and beyond)

Medical Monitor

This is an open-label, multicenter, sequential, 5-arm, phase 1 study of oral IXAZOMIB designed to assess drug-drug interaction with ketoconazole (Arm 1), the relative bioavailability of 2 capsule formulations of IXAZOMIB (Arm 2), food effect (Arm 3), drug-drug interaction with rifampin (Arm 4), and drug-drug interaction with clarithromycin (Arm 5) in participants with advanced nonhematologic malignancies or lymphoma.

Pharmacokinetics Study of Oral IXAZOMIB in Participants With Advanced Nonhematologic Malignancies or Lymphoma

A Phase 1 Study of Oral IXAZOMIB (MLN9708) to Assess Relative Bioavailability, Food Effect, Drug-Drug Interaction With Ketoconazole, Clarithromycin or Rifampin; and Safety and Tolerability in Patients With Advanced Nonhematologic Malignancies or Lymphoma

Best overall response for a participant is best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1: Complete response (CR) was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (\<) 10 millimeter \[mm\]). No new lesions. Partial response (PR) was defined as greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease (SD) was defined as not qualifying for CR, PR, Progressive Disease (PD). An increase of \>=20% from the nadir (or baseline, if it represents the point at which the sum of target disease was lowest) represents PD.

Millennium Pharmaceuticals, Inc.

At each visit, investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment.

Ixazomib 2.5 mg, capsule B, orally, once on Day 1 and 15 along with ketoconazole 400 mg, tablets, orally, once daily from Day 12 to 25 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants received ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg

Ixazomib 4 mg, capsule A, orally, once on Day 1 followed by ixazomib 4 mg, capsule B once on Day 15 of Cycle 1 (28-day treatment cycle) or ixazomib 4 mg, capsule B, orally, once on Day 1 followed by ixazomib 4 mg, capsule A once on Day 15 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants received ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Arm 2: Ixazomib 4 mg Capsule A or B

Ixazomib 4 mg, capsule B, orally, under fasted state, once on Day 1 followed by ixazomib 4 mg, capsule B, orally, under fed state, once on Day 15 of Cycle 1 (28-day treatment cycle) or ixazomib 4 mg, capsule B, orally, under fed state, once on Day 1 followed by ixazomib 4 mg, capsule B, orally, under fasted state, once on Day 15 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants received ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Arm 3: Ixazomib 4 mg Fasted or Fed

Ixazomib, 4 mg, capsule B, orally, once on Day 8 along with rifampin 600 mg, capsule, orally, once daily from Day 1 to 14 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants received ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Arm 4: Ixazomib 4 mg + Rifampin 600 mg

Ixazomib, 2.5 mg, capsule B, orally, once on Day 6 along with clarithromycin, 500 mg, tablet, orally, twice daily from Day 1 to 16 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants received ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg

Ixazomib 2.5 milligram (mg), capsule B, orally, once on Day 1 and 15 along with ketoconazole 400 mg, tablets, orally, once daily from Day 12 to 25 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants received ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Height

Weight

The safety population included all participants who received at least one dose of any study drug.

Medical Director

Ixazomib 2.5 mg, capsule B, orally, once on Day 1 of Cycle 1 (28-day treatment cycle).

Arm 1: Ixazomib 2.5 mg

Ixazomib 2.5 mg, capsule B, orally, once on Day 15 along with ketoconazole 400 mg, tablets, orally, once daily from Day 12 to 25 of Cycle 1 (28-day treatment cycle).

Ixazomib 4 mg, capsule A, orally, once on Day 1 or 15 of Cycle 1 (28-day treatment cycle).

Arm 2: Ixazomib 4 mg Capsule A

Ixazomib 4 mg, capsule B, orally, once on Day 1 or 15 of Cycle 1 (28-day treatment cycle).

Arm 2: Ixazomib 4 mg Capsule B

Ixazomib 4 mg, capsule B, orally, under fasted conditions, once on Day 1 or 15 of Cycle 1 (28-day treatment cycle).

Arm 3: Ixazomib 4 mg Fasted

Ixazomib 4 mg, capsule B, orally, under fed conditions, once on Day 1 or 15 of Cycle 1 (28-day treatment cycle).

Arm 3: Ixazomib 4 mg Fed

Ixazomib, 4 mg, capsule B, orally, once on Day 8 along with rifampin 600 mg, capsule, orally, once daily from Day 1 to 14 of Cycle 1 (21-day treatment cycle).

Ixazomib, 2.5 mg, capsule B, orally, once on Day 6 along with clarithromycin, 500 mg, tablet, orally, twice daily from Day 1 to 16 of Cycle 1 (21-day treatment cycle).

The pharmacokinetic (PK)-evaluable population included all participants who received protocol-specified dose in Cycle 1 without dose reductions/interruptions, did not receive any excluded concomitant medication during PK sampling, and had sufficient concentration-time data to permit estimation of PK parameters by noncompartmental analysis methods.

Cmax: Maximum Observed Plasma Concentration for Ixazomib

The PK-evaluable population included all participants who received protocol-specified dose in Cycle 1 without dose reductions/interruptions, did not receive any excluded concomitant medication during PK sampling, and had sufficient concentration-time data to permit estimation of PK parameters by noncompartmental analysis methods.

AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib

TEAEs

SAEs

Ixazomib, 4 mg, capsule B, orally, once on Day 8 along with rifampin 600 mg, capsule, orally, once daily from Day 1 to 14 of Cycle 1 (21-day treatment cycle). Participant received ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Ixazomib, 2.5 mg, capsule B, orally, once on Day 6 along with clarithromycin, 500 mg, tablet, orally, twice daily from Day 1 to 16 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants received ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles (28-day treatment cycle), until disease progression or unacceptable toxicity.

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Blood and lymphatic system disorders

Investigations

Metabolism and nutrition disorders

Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities

Number of Participants With Clinically Significant Vital Sign Abnormalities

The response-evaluable population included participants who had measurable disease at baseline, received at least 1 dose of any study drug, and had at least 1 postbaseline response assessment.

Percentage of Participants With Best Overall Response

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

Overall Study

Vinorelbine

Tubulin Modulators

Antimitotic Agents

vinorelbine tartrate

George Tidmarsh, MD, PhD

The purpose of this study is to determine the safety of oral administration of vinorelbine once daily for at least 7 days. The study will be conducted in subjects with a non-hematologic malignancy for which there are no currently accepted therapies.

Safety Study of Oral Vinorelbine in Subjects With Non-Hematologic Malignancies

A Phase 1 Study of the Safety, Pharmacokinetics, and Biological Activity of Metronomic Dosing With Orally Administered Vinorelbine Tablets in Subjects With Non-Hematologic Malignancies For Which There Are No Currently Accepted Therapies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pharmacokinetics Study of Oral IXAZOMIB in Participants With Advanced Nonhematologic Malignancies or Lymphoma	NCT01454076	Nonhematologic ... Lymphoma	Ixazomib 2.5 mg Ixazomib 4 mg C... Ixazomib 4 mg C... Ketoconazole Rifampin Clarithromycin Ixazomib 4 mg C...	18 Years -	Takeda
Safety Study of Oral Vinorelbine in Subjects With Non-Hematologic Malignancies	NCT00641160	Nonhematologic ...	vinorelbine tar... vinorelbine tar... vinorelbine tar...	18 Years -	Metronome Therapeutics

Spots Global Cancer Trial Database for nonhematologic malignancies