A research study that involves patients with a plasma cell cancer in the bone marrow. The study will determine the best dosing level with tolerable side effects of a new pharmaceutical compound with code CEP18770. The participating patients have had therapy but the disease came back and is now difficult to treat.

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2009-013778-41-BE
• Date of registration: 13/04/2010
• Prospective Registration: Yes
• Primary sponsor: Cephalon, Inc.
• Public title: A research study that involves patients with a plasma cell cancer in the bone marrow. The study will determine the best dosing level with tolerable side effects of a new pharmaceutical compound with code CEP18770. The participating patients have had therapy but the disease came back and is now difficult to treat.
• Scientific title: An Open-Label Study to Determine the Maximum Tolerated Dose and Evaluate the Efficacy and Safety of CEP-18770 in Patients With Relapsed Multiple Myeloma Refractory to the Most Recent Therapy.
• Date of first enrolment: 29/08/2011
• Target sample size: 86
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-013778-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Spain, United States

Contacts

• Name: Erik Peterson
• Affiliation: PPD Clinical

• Name: Erik Peterson
• Affiliation: PPD Clinical

Key inclusion & exclusion criteria

Inclusion criteria:
a- The patient has relapsed multiple myeloma that has progressed following therapies that included bortezomib and an IMiD (thalidomide or lenalidomide) either alone or in any combination.
b-The patient has multiple myeloma, which is refractory (ie, disease progression during or within 90 days of completing treatment) to the most recent therapy, bortezomib or IMiD, or any other chemotherapy, OR the patient did not tolerate and discontinued the most recent therapy for multiple myeloma but has recovered from its toxic effects.
c-The patient has measurable disease defined as 1 of the following:•serum M-protein = 0.5 g/dL•urine M-protein =200 mg/24 hours.
d-Written informed consent is obtained.
e-The patient is a man or woman at least 18 years of age.
f-The patient has a life expectancy of more than 3 months.
g-The patient has an ECOG performance status of 0, 1, or 2.
h-The patient has adequate hepatic organ function (<2.0 times the upper limit of normal [ULN] for total bilirubin, and <2.5 times ULN for [AST] and [ALT]).
i-The patient has an absolute neutrophil count (ANC) greater than 1 x 109/L, hemoglobin greater than 8.0 g/dL, and platelet count greater than 50 x 109/L.
j-The patient has been independent of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) support for more than 1 week.
k-The patient has been independent of platelet transfusion for more than 1 week.
l-The patient may have received an allogeneic and/or autologous transplant.
m-The patient has a creatinine clearance of 30 mL/minute or more as measured or as calculated based on the Cockcroft Gault method.
n-Women of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 3 months after participation in the study. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
o-The patient, if a man, is surgically sterile, or if sexually active with a woman of childbearing potential (as defined in criteria m above), is currently using an effective barrier method of contraception, and agrees to continue use of this method for the duration of the study and for 3 months after the last administration of study drug.
p-The patient must be willing and able to receive outpatient treatment and laboratory monitoring at the study center where study drug is administered.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66

Exclusion criteria:
a-The patient has nonmeasurable multiple myeloma, defined as less than 0.5 g/dL M-protein in serum and less than 200 mg/24 hours M-protein in urine.
b-The patient received glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last 2 weeks prior to the first dose of study drug.
c-The patient has POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy or monoclonal proliferative disorder, and skin changes [increased skin pigment, increased body hair, thickening of the skin, whitening of the nails, etc]).
d-The patient has plasma cell leukemia.
e1-The patient received chemotherapy with approved or investigative anticancer therapeutics within 2 weeks or within 5 drug half-lives (t1/2) or investigative anticancer therapeutics within 4 weeks or within 5 drug half-lives (t1/2) before the first dose of study drug, whichever time is greater
f-The patient received radiation therapy or immunotherapy in the 4 weeks or localized radiation therapy within 1 week prior to the first dose of study drug.
g-The patient received prior treatment with CEP 18770.
h-The patient has used a medication known to be a potent inducer of CYP2E1, CYP2D6 or CYP3A4/5 within 4 weeks prior to the first dose of study drug.
i-The patient has used a medication known to be a potent inhibitor of CYP2E1, CYP2D6 or CYP3A4/5 within 2 weeks prior to the first dose of study drug.
j-The patient had major surgery within 3 weeks before the first dose of study drug.
k-The patient has congestive heart failure (New York Heart Association Class III to IV) or had symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within the last 6 months.
l-The patient had an acute infection requiring systemic antibiotics, antiviral agents, or antifungal agents within 2 weeks before the first dose of study drug.
m-The patient has a known or suspected human immunodeficiency virus (HIV) infection on the basis of medical history.
n-The patient had a nonhematologic malignancy within the past 3 years except for the following: adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or breast, or prostate cancer (Gleason grade <6 with prostate specific antigen levels within the normal range).
o-The patient has myelodysplastic or myeloproliferative syndrome.
p-The patient has significant neuropathy (grade 3 or 4 or grade 2 with pain).
q-The patient is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
r-The patient has known central nervous system (CNS) involvement.
s-The patient has any serious psychiatric or medical condition that could interfere with treatment or study procedures, place the patient at unacceptable risk, or confound the ability of investigators to interpret study data.
t-The patient has known hypersensitivity to mannitol or hydroxypropyl betadex.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with relapsed multiple myeloma refractory to the most recent therapy.
MedDRA version: 14.1 Level: PT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: HLT Classification code 10028229 Term: Multiple myelomas System Organ Class: 10005329 - Blood and lymphatic system disorders

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Code: CEP-18770
Pharmaceutical Form: Powder for solution for injection
CAS Number: 847499-27-8
Current Sponsor code: CEP-18770
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Main Objective: The primary objective
part 1 : to determine the maximum tolerated dose of CEP-18770
part 2 : to evaluate the antitumor activity of CEP-18770 in patients treated at the MTD (2.1 mg/m2) including patients treated at the MTD (2.1 mg/m2) in part 1. The antitumor activity will be assessed by overall response rate (ORR) including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR), according to the International Myeloma Working Group criteria.

Primary end point(s): The primary efficacy measure is the patient’s best response to treatment with CEP 18770 during part 2 of the study (including patients treated at the MTD [2.1 mg/m2] in part 1).

Timepoint(s) of evaluation of this end point: N/A

Secondary Objective: The secondary objectives of the study are as follows:
• to evaluate the durability of response as determined by duration of response (DOR) to CEP 18770 (part 2 and patients treated at MTD [2.1 mg/m2] in part 1)
• to determine the time to response (TTR) to CEP 18770 (part 2 and patients treated at MTD [2.1 mg/m2] in part 1)
• to assess the time to progression (TTP) with CEP 18770 (part 2 and patients treated at MTD [2.1 mg/m2] in part 1)
• to further characterize the pharmacokinetics of CEP 18770 administered on days 1, 8, and 15 of a 28 day cycle
• to assess the exposure/response relationship of CEP-18770 and to assess whether there is a relationship between systemic exposure and relevant safety parameters
• to evaluate proteasome inhibition by CEP 18770
• to evaluate the safety of treatment with CEP 18770 administered intravenously on days 1, 8, and 15 of a 28 day cycle to patients with relapsed and refractory multiple myeloma.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy measures and endpoints for this study are as follows:
• the time from the date that criteria for response (sCR, CR, VGPR, or PR) to treatment with CEP 18770 are first met to the date of disease progression (duration of response [DOR])
• the time from the date of first dose of CEP 18770 to the date of first response (TTR) to treatment with CEP 18770
• the time from the date of first dose of CEP 18770 to the date of disease progression (TTP)

Timepoint(s) of evaluation of this end point: N/A

Secondary ID(s)

NCT01023880

C18770/2043

Source(s) of Monetary Support

Cephalon Inc