Hematological NeoplasmsPhase 1NCT02223052

Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

A Phase 1 study testing CC-486 and Vidaza in people with Hematological Neoplasms and Non-Hodgkin's Lymphoma, run by Celgene at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a Phase 1, open-label, multicenter, randomized, 2-stage crossover study consisting of 2 phases: Stage I - Pharmacokinetics (Bioequivalence), with an Extension Stage II - Pharmacokinetics (Food Effect) with an Extension This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hematological Neoplasms, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma
What is being tested?: CC-486 and Vidaza
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 89 participants
Where: 10 sitesUnited States
Study dates: 27 Oct 2014to 18 Dec 2018
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects must satisfy the following criteria to be enrolled in the study:
Age ≥ 18 years of age at the time of signing the informed consent document.
Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
Documented diagnosis of any of the following:
Myelodysplastic Syndrome (MDS) according to the World Health Organization (WHO) 2008 classification
Acute myeloid leukemia (AML)

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Multiple myeloma (MM), limited to those patients for whom standard curative or palliative treatments do not exist or are no longer effective
Non-Hodgkin's lymphoma (NHL), limited to those patients for whom standard curative or palliative treatment do not exist or are no longer effective,
Hodgkin's lymphoma (HL), limited to those patients for whom standard curative or palliative treatment do not exist or are no longer effective
Metastatic or inoperable solid tumors* (except gastrointestinal tumors or tumors that originated or metastasized to the liver) for which no standard treatment exists, or have progressed or recurred following prior therapy.
Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population.
Patients with a history of treated brain metastases should be clinically stable for ≥ 4 weeks prior to signing the informed consent. Glucocorticoid therapy for central nervous system (CNS) edema is permitted if ≤ 20 mg of prednisolone (or equivalent).
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
Have a life expectancy of ≥ 3 months.
Have stable renal function without dialysis for at least 2 months prior to Investigational Product (IP) administration defined by:
Serum creatinine < 2.5 x the upper limit of normal (ULN)
An average calculated creatinine clearance > 30 mL/min/1.73 m^2
Have organ and marrow function at the screening and pre-dose visits as defined by:
Hemoglobin ≥ 8 g/dL
Absolute neutrophil count (ANC) ≥ 0.75 x 10^3/uL without treatment with a myeloid growth factor within 3 days prior to first dose of IP
Platelets ≥ 30 x 10^3/uL
Total bilirubin ≤ 1.5 x Upper Limits of Normal (ULN)
Aspartate aminotransferase (AST) ≤ 2 x ULN
Alanine aminotransferase (ALT) ≤ 2 x ULN
Have a 12-lead Electrocardiogram (ECG) that is not clinically significant at screening, as determined by the investigator
Females of childbearing potential (FCBP) may participate, providing the subject meets the following conditions:
Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) or agree to practice true abstinence throughout the study, and for 3 months following the last dose of IP; and
Negative serum pregnancy test at screening (sensitivity of at least 25 mIU/mL); (Note that the screening serum pregnancy test can be used as the test prior to starting IP in the pharmacokinetics phase if it is performed within the 72-hour timeframe), and
Negative serum or urine pregnancy test (investigator's discretion; sensitivity of at least 25 mIU/mL) within 72 hours prior to starting IP in the extension phase. (Note: subjects must have negative serum or urine pregnancy test prior to dosing on Day 1 of each treatment cycle in the extension phase.)
Male subjects must:
Practice true abstinence* or agree to the use of at least two physician-approved contraceptive methods throughout the course of the study and should avoid fathering a child during the course of the study for at least 3 months following the last dose of IP.
True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception].
Able to adhere to the study visit schedule and other protocol requirements.

Who cannot join

Women who are pregnant or nursing (lactating).
Gastrointestinal tumors, tumors that have originated or metastasized to the liver, or other tumors known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
Had chemotherapy or radiotherapy within 4 weeks prior to the first day of Investigational Product (IP) administration.
Have been treated with an investigational agent within 4 weeks prior to the first day of IP administration.
Have ongoing clinically significant adverse event(s) due to prior treatments administered as determined by the investigator.
Significant active cardiac disease within the previous 6 months, including:

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New York Heart Association (NYHA) class IV congestive heart failure
Significant cardiac arrhythmia or unstable angina or angina requiring surgical or medical intervention; and/or
Myocardial infarction
Have known or suspected hypersensitivity to azacitidine or any other ingredient used in the manufacturing of Azacitidine.
Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
History of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis), celiac disease, prior gastrectomy, gastric bypass, upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity.
Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
Any condition that confounds the ability to interpret data from the study
Impaired ability to swallow oral medication
Any condition that confounds the ability to interpret data from the study

Trial locations and contacts

10 sites in 1 country.

City, postcode or hospital

10 sites in 1 country

United States10 sites

Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Henry Ford Health System
Detroit, Michigan, 48202-268
Greenville Hospital System
Greenville, South Carolina, 29605
The Methodist Hospital Research Institute l
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
Vanderbilt- Ingram Cancer Center
Nashville, Tennessee, 37232-6307
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Scottsdale Healthcare Research Institute
Scottsdale, Arizona, 85258
Mayo Clinic - Arizona
Scottsdale, Arizona, 85259
University of Arizona Cancer Center
Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Multicenter, Randomized, 2-Period, Crossover Study to Evaluate the Bioequivalence and Food Effect Bioavailability of CC-486 (Oral Azacitidine) Tablets in Adult Cancer Subjects

This is a Phase 1, open-label, multicenter, randomized, 2-stage crossover study consisting of 2 phases:

Stage I - Pharmacokinetics (Bioequivalence), with an Extension Stage II - Pharmacokinetics (Food Effect) with an Extension

This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver for which no standard treatment exists or have progressed or recurred following prior therapy. Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population. Approximately 23 sites in the US and 2 in Canada will participate in this study.

Read the detailed description

Stage I - Pharmacokinetics (Bioequivalence)

Subjects will be randomized to receive CC-486 300 mg orally on each of the two pharmacokinetic (PK) study days based on the dosing sequences they are randomized to:

Dosing Sequence 1: 2x150 mg tablets followed by 1x30 mg tablet. Dosing Sequence 2: 1x300 mg tablet followed by 2x150 mg tablets. Each dose will be administered in the clinic at least 48 hours apart between PK dosing day 1 and PK dosing day 2 over a period no longer than 10 days under fasted conditions.

Stage II - Pharmacokinetics (Food Effect)

Subjects will be randomized to receive CC-486 300 mg orally on each of the two PK study days based on the dosing sequences they are randomized to:

Dosing Sequence 1: 1x300 mg tablet under fasted condition followed by 1x300 mg tablet under fed condition.

Dosing Sequence 2: 1x300 mg tablet under fed condition followed by 1x300 mg tablet under fasted condition.

Each dose will be administered in the clinic at least 48 hours apart between PK dosing day 1 and PK dosing day 2 over a period no longer than 10 days. The sponsor will generate the randomization scheme and assign subjects upon enrollment to the appropriate sequence for dosing:

Fasted condition: following an overnight fast of at least 10 hours, subjects will ingest oral Azacitidine with 240 mL of room temperature water. Subjects must fast for a minimum of 4 hours following oral Azacitidine administration. Subjects may drink water as desired, except for 1 hour before and 1 hour after oral Azacitidine administration.

Fed condition: following an overnight fast of at least 10 hours and following the performance of all required pre-dose assessments, subjects randomized to receive test medication in a fed state will begin ingesting a breakfast meal 30 (±5) minutes prior to the planned administration of oral Azacitidine. They will continue the entire meal within 20 to 25 minutes (no less than 20 minutes) from the time the meal is served. Subjects will then ingest oral Azacitidine with 240 mL of room temperature water. Subjects must fast a minimum of 4 hours following oral Azacitidine administration. Subjects may drink water as desired, except for 1 hour before and 1 hour after administration of oral Azacitidine.

Extension Phase (for subjects who have completed PK Stage I or Stage II) Subjects continuing beyond the pharmacokinetics phase (Stage I or Stage II) will enter the extension phase of the study at the discretion of the investigator to receive < 6 (four-week) cycles of Vidaza 75 mg/m2 IV or SC daily for 7 days in the clinic and repeat every 4 weeks per prescribed label at the discretion of the investigator for ≤ 6 (four-week) cycles.

Conditions: Hematological Neoplasms, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoma, Multiple Myeloma, Acute Myeloid Leukemia
Being tested: CC-486, Vidaza
Keywords: CC-486, Oral Azacitidine, Soli Tumor Malignancy, Hematological Malignancy, Leukemia, Lymphoma, Multiple Myeloma, Acute Myeloid Leukemia, Myelodysplastic Syndromes, Neoplasms, Melanoma, Breast Cancer, Metastatic Breast Cancer, Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Renal Cell Carcinoma, Glioblastoma Multiforme, Brain Cancer, Kidney Cancer, Lung cancer
Medical subject headings: Hematologic Neoplasms, Lymphoma, Non-Hodgkin, Hodgkin Disease, Lymphoma, Multiple Myeloma, Leukemia, Myeloid, Acute, Leukemia, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CC-486Drug
Also called Oral Azacitdine
Arm 1: Two 150-mg tablets of CC-486 on Day 1 and 1 x 300 mg CC-486 on Day 2 Arm 2: 1 x 300mg tablet of CC 486 on Day 1 and 2 x 150mg CC-486 on Day 2
VidazaDrug
Also called Azacitidine for Injection, AZA
75mg/m^2 IV or SC daily x 7 days every 4 weeks for ≤ 6 (four-week) cycles

Study groups in NCT02223052
Study group	Role	What they receive
CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1	Experimental	Two 150-mg tablets of CC-486 under fasting condition on PK dosing Day 1, followed by one 300-mg tablet of CC-486 on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered. Receives: Drug: CC-486; Drug: Vidaza
CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 1	Experimental	One 300-mg tablet of oral CC-486 under fasting condition on PK dosing Day 1, followed by one 300-mg tablet of oral CC-486 under fed condition on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered. Receives: Drug: CC-486; Drug: Vidaza
CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 2	Experimental	One 300-mg tablets of CC-486 under fasting condition on PK dosing Day 1, followed by two 150-mg tablets on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered. Receives: Drug: CC-486; Drug: Vidaza
CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 2	Experimental	One 300-mg tablet of oral CC-486 under fed condition on PK dosing Day 1, followed by one tablet of 300-mg oral CC-486 under fasted conditions on PK dosing Day 2; if PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine of Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered. Receives: Drug: CC-486; Drug: Vidaza

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacokinetics Cmax - Stage I (Bioequivalence)
The observed maximum concentration
Measured: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Pharmacokinetics Tmax - Stage I (Bioequivalence)
The observed time to first maximum concentration
Measured: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Pharmacokinetics AUC-t - Stage I (Bioequivalence)
Area under the concentration-time curve from time zero to the last quantifiable time point calculated by the linear trapezoidal rule
Measured: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Pharmacokinetics AUC-infinity - Stage I (Bioequivalence)
Area under the concentration time-curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity. It will be calculated as AUC∞ = [AUCt + Ct/λz]. Ct is the last quantifiable concentration
Measured: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Pharmacokinetics λz (Terminal Rate) - Stage I (Bioequivalence)
Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear concentration-time curve
Measured: Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.3.5, 4, 6, and 8 hours post-dose
Pharmacokinetics Terminal Half-Life (t½) - Stage I (Bioequivalence)
Terminal phase half-life, calculated according to the following equation: t½ = 0.693/λz
Measured: Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Pharmacokinetics Apparent total clearance (CL/F) - Stage I (Bioequivalence)
Apparent total clearance, calculated as Dose/AUC∞
Measured: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Pharmacokinetics Apparent volume of distribution (Vd/F) - Stage I (Bioequivalence)
Apparent volume of distribution, calculated according to the equation: Vd/F = (CL/F) / λz
Measured: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Pharmacokinetics Cmax - Stage II (Food Effect Bioavailability)
The observed maximum concentration
Measured: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Pharmacokinetics Tmax - Stage II (Food Effect Bioavailability)
The observed time to first maximum concentration
Measured: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Pharmacokinetics AUC-t - Stage II (Food Effect Bioavailability)
Area under the concentration-time curve from time zero to the last quantifiable time point calculated by the linear trapezoidal rule.
Measured: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Pharmacokinetics AUC-infinity - Stage II (Food Effect Bioavailability)
Area under the concentration time-curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity. It will be calculated as AUC∞ = [AUCt + Ct/λz]. Ct is the last quantifiable concentration.
Measured: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Pharmacokinetics λz (Terminal Rate) - Stage II (Food Effect Bioavailability)
Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear concentration-time curve
Measured: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Pharmacokinetics Terminal Half-Life (t½) - Stage II (Food Effect Bioavailability)
Terminal phase half-life, calculated according to the following equation: t½ = 0.693/λz
Measured: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Pharmacokinetics Apparent total clearance (CL/F) - Stage II (Food Effect Bioavailability)
Apparent total clearance, calculated as Dose/AUC∞
Measured: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Pharmacokinetics Apparent volume of distribution (Vd/F) - Stage II (Food Effect Bioavailability)
Apparent volume of distribution, calculated according to the equation: Vd/F = (CL/F) / λz
Measured: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.

Secondary outcomes (1)

Adverse Events (AEs)
Adverse Event (AE) is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a pre-existing condition) should be considered an AE.
Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Oct 201418 Dec 2018

First posted22 Aug 2014 (estimated)
Study start27 Oct 2014
Primary completion11 Jun 2018
Study completion18 Dec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Hematological NeoplasmsStudies of the same condition, open and under way.
More trials run by CelgeneThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 89 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02223052
Sponsor's protocol ID: CC-486-CAGEN-001
Status last verified: May 2020
First submitted: 20 Aug 2014
Last updated: 12 May 2020
Results posted: No
Data monitoring committee: No
Expanded access: Available

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 12 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-label, Multicenter, Randomized, 2-Period, Crossover Study to Evaluate the Bioequivalence and Food Effect Bioavailability of CC-486 (Oral Azacitidine) Tablets in Adult Cancer Subjects
ClinicalTrials.gov ID: NCT02223052
Acronym / sponsor ID: CC-486-CAGEN-001
Conditions: Hematological Neoplasms, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoma, Multiple Myeloma, Acute Myeloid Leukemia
Keywords: CC-486, Oral Azacitidine, Soli Tumor Malignancy, Hematological Malignancy, Leukemia, Lymphoma, Multiple Myeloma, Acute Myeloid Leukemia
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 89 participants (actual)
Lead sponsor: CelgeneIndustry (pharma, biotech, devices)
Study start: 27 Oct 2014 (actual)
Primary completion: 11 Jun 2018 (actual)
Study completion: 18 Dec 2018 (actual)
First posted: 22 Aug 2014 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This is a Phase 1, open-label, multicenter, randomized, 2-stage crossover study consisting of 2 phases:

Stage I - Pharmacokinetics (Bioequivalence), with an Extension Stage II - Pharmacokinetics (Food Effect) with an Extension

Detailed description

Stage I - Pharmacokinetics (Bioequivalence)

Subjects will be randomized to receive CC-486 300 mg orally on each of the two pharmacokinetic (PK) study days based on the dosing sequences they are randomized to:

Stage II - Pharmacokinetics (Food Effect)

Subjects will be randomized to receive CC-486 300 mg orally on each of the two PK study days based on the dosing sequences they are randomized to:

Dosing Sequence 1: 1x300 mg tablet under fasted condition followed by 1x300 mg tablet under fed condition.

Dosing Sequence 2: 1x300 mg tablet under fed condition followed by 1x300 mg tablet under fasted condition.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1	Experimental	Drug: CC-486, Drug: VidazaTwo 150-mg tablets of CC-486 under fasting condition on PK dosing Day 1, followed by one 300-mg tablet of CC-486 on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.
CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 1	Experimental	Drug: CC-486, Drug: VidazaOne 300-mg tablet of oral CC-486 under fasting condition on PK dosing Day 1, followed by one 300-mg tablet of oral CC-486 under fed condition on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.
CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 2	Experimental	Drug: CC-486, Drug: VidazaOne 300-mg tablets of CC-486 under fasting condition on PK dosing Day 1, followed by two 150-mg tablets on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.
CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 2	Experimental	Drug: CC-486, Drug: VidazaOne 300-mg tablet of oral CC-486 under fed condition on PK dosing Day 1, followed by one tablet of 300-mg oral CC-486 under fasted conditions on PK dosing Day 2; if PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine of Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (33 listed)

Subjects must satisfy the following criteria to be enrolled in the study:

Key exclusion criteria (17 listed)

Women who are pregnant or nursing (lactating).
Gastrointestinal tumors, tumors that have originated or metastasized to the liver, or other tumors known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
Had chemotherapy or radiotherapy within 4 weeks prior to the first day of Investigational Product (IP) administration.
Have been treated with an investigational agent within 4 weeks prior to the first day of IP administration.
Have ongoing clinically significant adverse event(s) due to prior treatments administered as determined by the investigator.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CC-486Also: Oral AzacitdineArm 1: Two 150-mg tablets of CC-486 on Day 1 and 1 x 300 mg CC-486 on Day 2 Arm 2: 1 x 300mg tablet of CC 486 on Day 1 and 2 x 150mg CC-486 on Day 2	Drug	CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1, CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 2, CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 1, CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 2
VidazaAlso: Azacitidine for Injection, AZA75mg/m^2 IV or SC daily x 7 days every 4 weeks for ≤ 6 (four-week) cycles	Drug	CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1, CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 2, CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 1, CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 2

Primary outcome

Pharmacokinetics Cmax - Stage I (Bioequivalence)
Time frame: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
The observed maximum concentration
Pharmacokinetics Tmax - Stage I (Bioequivalence)
Time frame: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
The observed time to first maximum concentration
Pharmacokinetics AUC-t - Stage I (Bioequivalence)
Time frame: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Area under the concentration-time curve from time zero to the last quantifiable time point calculated by the linear trapezoidal rule
Pharmacokinetics AUC-infinity - Stage I (Bioequivalence)
Time frame: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Area under the concentration time-curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity. It will be calculated as AUC∞ = [AUCt + Ct/λz]. Ct is the last quantifiable concentration
Pharmacokinetics λz (Terminal Rate) - Stage I (Bioequivalence)
Time frame: Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.3.5, 4, 6, and 8 hours post-dose
Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear concentration-time curve
Pharmacokinetics Terminal Half-Life (t½) - Stage I (Bioequivalence)
Time frame: Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Terminal phase half-life, calculated according to the following equation: t½ = 0.693/λz
Pharmacokinetics Apparent total clearance (CL/F) - Stage I (Bioequivalence)
Time frame: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Apparent total clearance, calculated as Dose/AUC∞
Pharmacokinetics Apparent volume of distribution (Vd/F) - Stage I (Bioequivalence)
Time frame: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Apparent volume of distribution, calculated according to the equation: Vd/F = (CL/F) / λz
Pharmacokinetics Cmax - Stage II (Food Effect Bioavailability)
Time frame: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
The observed maximum concentration
Pharmacokinetics Tmax - Stage II (Food Effect Bioavailability)
Time frame: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
The observed time to first maximum concentration
Pharmacokinetics AUC-t - Stage II (Food Effect Bioavailability)
Time frame: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Area under the concentration-time curve from time zero to the last quantifiable time point calculated by the linear trapezoidal rule.
Pharmacokinetics AUC-infinity - Stage II (Food Effect Bioavailability)
Time frame: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Area under the concentration time-curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity. It will be calculated as AUC∞ = [AUCt + Ct/λz]. Ct is the last quantifiable concentration.
Pharmacokinetics λz (Terminal Rate) - Stage II (Food Effect Bioavailability)
Time frame: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear concentration-time curve
Pharmacokinetics Terminal Half-Life (t½) - Stage II (Food Effect Bioavailability)
Time frame: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Terminal phase half-life, calculated according to the following equation: t½ = 0.693/λz
Pharmacokinetics Apparent total clearance (CL/F) - Stage II (Food Effect Bioavailability)
Time frame: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Apparent total clearance, calculated as Dose/AUC∞
Pharmacokinetics Apparent volume of distribution (Vd/F) - Stage II (Food Effect Bioavailability)
Time frame: PK Dosing Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose.
Apparent volume of distribution, calculated according to the equation: Vd/F = (CL/F) / λz

1 secondary outcome

Adverse Events (AEs)
Time frame: Up to 18 months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2020.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Du Lam, MD study director

Celgene

10 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CC-486 and Vidaza in people with Hematological Neoplasms and Non-Hodgkin's Lymphoma, run by Celgene at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics Cmax - Stage I (Bioequivalence) (time frame: Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02223052.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2020.