A Phase 1 interventional study of Irinotecan and Pevonedistat in Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm and Recurrent Primary Central Nervous System Neoplasm, sponsored by Children's Oncology Group. Completed at 20 sites in United States. Open to participants aged 6 Months to 21 Years. Per ClinicalTrials.gov, last updated 2024-10-22.
Sponsored by Children's Oncology Group · Phase 1, Interventional, and Treatment
This phase I trial studies the side effects and best dose of pevonedistat when given together with irinotecan hydrochloride and temozolomide in treating patients with solid tumors, central nervous system (CNS) tumors, or lymphoma that have come back after a period of improvement (recurrent) or that do not respond to treatment (refractory). Pevonedistat and irinotecan may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, 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. Giving pevonedistat, irinotecan hydrochloride, and temozolomide may work better in treating patients with solid tumors, central nervous system (CNS) tumors, or lymphoma compared to irinotecan and temozolomide alone.
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of pevonedistat administered as an intravenous infusion on days 1, 8, 10, and 12 of a 28-day cycle (cycle 1), and on days 1, 3, and 5 of a 21-day cycle (cycle 2 and beyond) in combination with irinotecan (administered as an intravenous infusion on days 8-12 of cycle 1 and days 1-5 of cycles 2+) and temozolomide (administered orally on days 8-12 in cycle 1 and days 1-5 of cycles 2+) in children with recurrent or refractory solid tumors, including central nervous system (CNS) tumors and lymphoma.
II. To define and describe the toxicities of pevonedistat administered on this schedule.
III. To characterize the pharmacokinetics of pevonedistat in children with recurrent or refractory cancer.
SECONDARY OBJECTIVES:
I. To preliminarily define the antitumor activity of pevonedistat within the confines of a phase 1 study.
II. To assess the biologic activity of pevonedistat.
OUTLINE: This is a dose escalation study of pevonedistat.
Patients receive pevonedistat intravenously (IV) over 60 minutes on days 1, 8, 10, and 12, temozolomide orally (PO) daily on days 8-12, and irinotecan IV over 90 minutes on days 8-12 of cycle 1. Beginning cycle 2, patients receive pevonedistat IV over 60 minutes on days 1, 3, and 5, temozolomide PO daily on days 1-5, and irinotecan IV over 90 minutes on days 1-5. Treatment repeats every 28 days for cycle 1 and 21 days for subsequent cycles for up to 17 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
3,018 studies on the registry are indexed under Lymphoma; 434 are open to participants now.
This study's enrollment of 30 is below the median of 43 across 2,319 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →Children's Oncology Group is the lead sponsor of 448 studies on the registry; 36 are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required time frame, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
Stem cell Infusions (with or without total body irradiation [TBI]):
For patients with solid tumors without known bone marrow involvement:
or radioisotope (GFR) >= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
Exclusion Criteria:
Patients with known cardiopulmonary disease are not eligible; cardiopulmonary disease is defined as:
arrhythmia:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive pevonedistat IV over 60 minutes on days 1, 8, 10, and 12, temozolomide PO daily on days 8-12, and irinotecan IV over 90 minutes on days 8-12 of cycle 1. Beginning cycle 2, patients receive pevonedistat IV over 60 minutes on days 1, 3, and 5, temozolomide PO daily on days 1-5, and irinotecan IV over 90 minutes on days 1-5. Treatment repeats every 28 days for cycle 1 and 21 days for subsequent cycles for up to 17 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Irinotecan · Drug: Pevonedistat · Drug: Temozolomide
Given IV
Given IV
Also known as: MLN4924, Nedd8-Activating Enzyme Inhibitor MLN4924
Given PO
Also known as: CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temizole, Temodal, Temodar, Temomedac, TMZ
MTD/RP2D of Pevonedistat in Combination With Irinotecan and Temozolomide
The maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) will be the maximum dose at which fewer than one-third of patients experience dose limiting toxicities.
Time frame: Up to 28 days
Number of Participants With Grade 3 or Greater Toxicities Associated With Pevonedistat in Combination With Irinotecan and Temozolomide
Frequency of patients who experience at least one grade 3 or higher toxicity that is at least possibly attributable to pevonedistat using the Common Terminology Criteria for Adverse Events version 5.0 by dose level stratified by study part and dose level.
Time frame: Up to 3 years 8 months
Half-life of Pevonedistat in Combination With Irinotecan and Temozolomide
Median (Range) for the time required for the serum concentration to fall to 50% of its starting dose by dose level stratified by study part and dose level.
Time frame: Up to 10 days
T Max of Pevonedistat in Combination With Irinotecan and Temozolomide
Median (Range) for the time at which the maximum (peak) serum concentration occurs by dose level stratified by study part and dose level.
Time frame: Up to 10 days
C Max of Pevonedistat in Combination With Irinotecan and Temozolomide
Median (Range) for the maximum (peak) serum concentration by dose level stratified by study part and dose level.
Time frame: Up to 10 days
AUC of Pevonedistat in Combination With Irinotecan and Temozolomide
Median (range) of the area under the drug concentration over time (pre-dose and then 0, 1, 2, 4, 6-8, and 24-hours post-dose infusion) curve stratified by study part and dose level.
Time frame: Up to 10 days
Clearance of Pevonedistat in Combination With Irinotecan and Temozolomide
Median (Range) for the rate of elimination of the drug by dose level stratified by study part and dose level.
Time frame: Up to 10 days
Anti-tumor Activity of Pevonedistat in Combination With Irinotecan and Temozolomide
Frequency of disease response (best overall response of partial or complete response) assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR by dose level.
Time frame: Up to 4 years
| Milestone | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 |
|---|---|---|---|---|---|
| Started | 6 | 6 | 6 | 6 | 6 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 6 | 6 | 6 | 6 | 6 |
| Withdrew: Lack of efficacy | 5 | 5 | 6 | 5 | 5 |
| Withdrew: Physician decision | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 1 | 1 | 0 | 1 | 0 |
The maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) will be the maximum dose at which fewer than one-third of patients experience dose limiting toxicities.
| mg/m^2 | Treatment (Pevonedistat, Temozolomide, Irinotecan) |
|---|---|
| MTD/RP2D of Pevonedistat in Combination With Irinotecan and Temozolomide | 35 |
Frequency of patients who experience at least one grade 3 or higher toxicity that is at least possibly attributable to pevonedistat using the Common Terminology Criteria for Adverse Events version 5.0 by dose level stratified by study part and dose level.
| Participants | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 |
|---|---|---|---|---|---|
| Number of Participants With Grade 3 or Greater Toxicities Associated With Pevonedistat in Combination With Irinotecan and Temozolomide | 5 | 4 | 6 | 2 | 4 |
Median (Range) for the time required for the serum concentration to fall to 50% of its starting dose by dose level stratified by study part and dose level.
| hours | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 |
|---|---|---|---|---|---|
| Half-life of Pevonedistat in Combination With Irinotecan and Temozolomide | 5.3 (4.7 to 7.4) | 5 (4.1 to 6.0) | 5.2 (4.0 to 5.5) | 4.7 (4.0 to 6.7) | 6.1 (3.9 to 7.9) |
Median (Range) for the time at which the maximum (peak) serum concentration occurs by dose level stratified by study part and dose level.
| hours | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 |
|---|---|---|---|---|---|
| T Max of Pevonedistat in Combination With Irinotecan and Temozolomide | 1. (1.0 to 1.6) | 1 (1.0 to 2.5) | 1 (0.9 to 1.4) | 1.1 (1.0 to 1.1) | 1.1 (1.0 to 1.5) |
Median (Range) for the maximum (peak) serum concentration by dose level stratified by study part and dose level.
| ng/mL | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 |
|---|---|---|---|---|---|
| C Max of Pevonedistat in Combination With Irinotecan and Temozolomide | 156 (87.9 to 208.0) | 218.5 (170.5 to 335.0) | 303.5 (174.0 to 365.5) | 419 (238.0 to 689.0) | 363.8 (214.0 to 2367.0) |
Median (range) of the area under the drug concentration over time (pre-dose and then 0, 1, 2, 4, 6-8, and 24-hours post-dose infusion) curve stratified by study part and dose level.
| hr*ng/mL | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 |
|---|---|---|---|---|---|
| AUC of Pevonedistat in Combination With Irinotecan and Temozolomide | 803 (608.0 to 1010.0) | 973.5 (865.0 to 1928.0) | 1340 (990.0 to 1890.0) | 2018.5 (1505.0 to 2535.0) | 1957 (1583.0 to 5733.0) |
Median (Range) for the rate of elimination of the drug by dose level stratified by study part and dose level.
| L/hr/m^2 | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 |
|---|---|---|---|---|---|
| Clearance of Pevonedistat in Combination With Irinotecan and Temozolomide | 18.8 (14.8 to 24.7) | 20.8 (10.6 to 23.3) | 18.9 (13.2 to 25.4) | 17.5 (13.8 to 23.3) | 17.9 (10.2 to 22.1) |
Frequency of disease response (best overall response of partial or complete response) assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR by dose level.
| Participants | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 |
|---|---|---|---|---|---|
| Anti-tumor Activity of Pevonedistat in Combination With Irinotecan and Temozolomide | 1 | 1 | 0 | 0 | 0 |
Collected over Up to 4 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part A Dose Level 1: 15 mg/m^2 | 0/6 (0%) | 5/6 (83.3%) | 6/6 (100%) |
| Part A Dose Level 2: 20 mg/m^2 | 0/6 (0%) | 4/6 (66.7%) | 6/6 (100%) |
| Part A Dose Level 3: 25 mg/m^2 | 0/6 (0%) | 6/6 (100%) | 6/6 (100%) |
| Part A Dose Level 4: 35 mg/m^2 | 0/6 (0%) | 2/6 (33.3%) | 6/6 (100%) |
| Part A PK Dose Level 4: 35 mg/m^2 | 0/6 (0%) | 4/6 (66.7%) | 6/6 (100%) |
| Event | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 |
|---|---|---|---|---|---|
| Lymphocyte count decreasedInvestigations | 5/6 | 0/6 | 2/6 | 1/6 | 3/6 |
| White blood cell decreasedInvestigations | 5/6 | 0/6 | 1/6 | 1/6 | 1/6 |
| Neutrophil count decreasedInvestigations | 3/6 | 1/6 | 2/6 | 2/6 | 1/6 |
| Alanine aminotransferase increasedInvestigations | 0/6 | 2/6 | 1/6 | 0/6 | 1/6 |
| HyperglycemiaMetabolism and nutrition disorders | 0/6 | 0/6 | 2/6 | 0/6 | 0/6 |
| HypokalemiaMetabolism and nutrition disorders | 0/6 | 0/6 | 2/6 | 0/6 | 1/6 |
| Abdominal painGastrointestinal disorders | 0/6 | 0/6 | 0/6 | 0/6 | 1/6 |
| AnemiaBlood and lymphatic system disorders | 0/6 | 1/6 | 0/6 | 1/6 | 0/6 |
| AnorexiaMetabolism and nutrition disorders | 1/6 | 0/6 | 1/6 | 0/6 | 0/6 |
| Aspartate aminotransferase increasedInvestigations | 0/6 | 0/6 | 1/6 | 0/6 | 0/6 |
| Event | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 |
|---|---|---|---|---|---|
| AnemiaBlood and lymphatic system disorders | 6/6 | 4/6 | 6/6 | 6/6 | 5/6 |
| Aspartate aminotransferase increasedInvestigations | 1/6 | 6/6 | 5/6 | 2/6 | 4/6 |
| DiarrheaGastrointestinal disorders | 4/6 | 4/6 | 6/6 | 3/6 | 2/6 |
| NauseaGastrointestinal disorders | 6/6 | 5/6 | 4/6 | 3/6 | 4/6 |
| Platelet count decreasedInvestigations | 3/6 | 4/6 | 4/6 | 1/6 | 6/6 |
| White blood cell decreasedInvestigations | 5/6 | 6/6 | 5/6 | 6/6 | 5/6 |
| Alanine aminotransferase increasedInvestigations | 4/6 | 5/6 | 5/6 | 4/6 | 3/6 |
| FatigueGeneral disorders | 4/6 | 3/6 | 2/6 | 3/6 | 5/6 |
| HypoalbuminemiaMetabolism and nutrition disorders | 3/6 | 0/6 | 4/6 | 2/6 | 5/6 |
| VomitingGastrointestinal disorders | 5/6 | 4/6 | 4/6 | 2/6 | 5/6 |
| Age, Categorical(Participants) | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 | Total |
|---|---|---|---|---|---|---|
| <=18 years | 6 | 6 | 4 | 6 | 6 | 28 |
| Between 18 and 65 years | 0 | 0 | 2 | 0 | 0 | 2 |
| >=65 years | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 | Total |
|---|---|---|---|---|---|---|
| Median | 14.5 (6 to 18) | 12 (1 to 17) | 11 (2 to 21) | 7 (5 to 15) | 16.5 (4 to 18) | 13 (1 to 21) |
| Sex: Female, Male(Participants) | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 | Total |
|---|---|---|---|---|---|---|
| Female | 1 | 2 | 4 | 1 | 3 | 11 |
| Male | 5 | 4 | 2 | 5 | 3 | 19 |
| Ethnicity (NIH/OMB)(Participants) | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 | Total |
|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 1 | 2 | 2 | 5 |
| Not Hispanic or Latino | 5 | 6 | 5 | 4 | 4 | 24 |
| Unknown or Not Reported | 1 | 0 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB)(Participants) | Part A Dose Level 1: 15 mg/m^2 | Part A Dose Level 2: 20 mg/m^2 | Part A Dose Level 3: 25 mg/m^2 | Part A Dose Level 4: 35 mg/m^2 | Part A PK Dose Level 4: 35 mg/m^2 | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 1 | 0 | 0 | 1 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 2 | 0 | 3 | 6 |
| White | 5 | 3 | 3 | 5 | 2 | 18 |
| More than one race | 0 | 0 | 1 | 0 | 0 | 1 |
| Unknown or Not Reported | 1 | 1 | 0 | 1 | 0 | 3 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Jan 2018 to primary completion in Sep 2021, 44 months.
Results were first posted in Sep 2022, 11 months after primary completion.
Of 138 non-industry phase 1 interventional studies under Lymphoma, half reached primary completion within 64 months of starting (the median), counting those still running; a quarter within 39 and three quarters within 88. This study's 44 months is below that.
Counting every sponsor, half of 281 studies reached it within 53 months; a quarter within 34 and three quarters within 77.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Oct 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Irinotecan · Pevonedistat · Temozolomide