CEP-18770 in Combination With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier:
NCT01348919
First received: May 4, 2011
Last updated: August 30, 2013
Last verified: August 2013
  Purpose

The primary objective of the study is to determine the maximum tolerated dose (MTD) of CEP-18770 in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma.


Condition Intervention Phase
Multiple Myeloma
Drug: CEP-18770
Drug: Lenalidomide
Drug: Dexamethasone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Study to Determine the Maximum Tolerated Dose and Evaluate the Safety and Efficacy of CEP-18770 in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • The patient's best response to treatment with CEP-18770 in combination with lenalidomide and dexamethasone [ Time Frame: Baseline to endpoint (defined as a maximum of 1 year after first administration of CEP-18770 or until disease progression) ] [ Designated as safety issue: No ]
    The primary efficacy variable is the overall response rate (ORR) defined as the number of patients in the full analysis set achieving a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) during the study divided by the total number of patients in the full analysis set.

  • Determination of the maximum tolerated dose (MTD) of CEP-18770 in combination with lenalidomide and dexamethasone in patients with refractory or relapsed multiple myeloma [ Time Frame: Days 1 to 28 of cycle 1 ] [ Designated as safety issue: Yes ]
    The maximum tolerated dose will be determined based on the observation of dose limiting toxicities during cycle 1 of each dosing cohort.


Secondary Outcome Measures:
  • Time interval from the date of first response to the date of disease progression [ Time Frame: baseline to endpoint (defined as a maximum of 1 year after first administration of CEP-18770 or until disease progression) ] [ Designated as safety issue: No ]
  • Time interval from the date of first dose to the date of disease progression [ Time Frame: Baseline to endpoint (defined as a maximum of 1 year after first administration of CEP-18770 or until disease progression) ] [ Designated as safety issue: No ]
  • Evaluation of the safety and tolerability of CEP-18770 in combination with lenalidomide and dexamethasone [ Time Frame: During the entire study treatment period of approximately 48 weeks (twelve 28-day cycles) ] [ Designated as safety issue: Yes ]
    Assessed by the occurrence of adverse events, clinical laboratory test results, vital sign measurements, electrocardiogram (ECG) findings, physical examination findings, and concomitant medication usage.

  • Cmax pharmacokinetic parameter [ Time Frame: Cycle 1 days 1, 8, and 15 in Part 1 and Days 1, 3, 8, 15, and days 17 to 19 in Part 2 ] [ Designated as safety issue: No ]
    maximum observed drug concentration (Cmax)

  • tmax pharmacokinetic parameter [ Time Frame: Cycle 1 days 1, 8, and 15 in Part 1 and Days 1, 3, 8, 15, and days 17 to 19 in Part 2 ] [ Designated as safety issue: No ]
    time to maximum observed drug concentration (tmax)

  • AUC pharmacokinetic parameter [ Time Frame: Cycle 1 days 1, 8, and 15 in Part 1 and Days 1, 3, 8, 15, and days 17 to 19 in Part 2 ] [ Designated as safety issue: No ]
    area under the plasma concentration-time curve (AUC)


Enrollment: 11
Study Start Date: August 2011
Study Completion Date: May 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CEP-18770 in Combination With Lenalidomide and Dexamethasone Drug: CEP-18770
administered on days 1, 8, and 15 of each 28-day cycle
Drug: Lenalidomide
administered 25 mg on days 1 through 21 of each 28-day cycle
Drug: Dexamethasone
administered 40 mg on days 1, 8, 15, and 22 of each 28-day cycle

Detailed Description:

After cycle 1, the start of treatment in each cycle may occur within a 3-day window. In addition, after cycle 2, the start of treatment in cycle 3 may be delayed by 1 week if, in the opinion of the investigator, the delay is warranted. If a patient cannot receive 75% of the planned dose for any of the 3 agents (missing more than 1 dose of CEP-18770, or more than 5 doses of lenalidomide [either consecutively or separately], or more than 1 dose of dexamethasone [either consecutively or separately]), due to a drug-related adverse event, the event will be considered a dose limiting toxicity (DLT), even if the grade of toxicity is lower than specified DLT determination. Patients will receive intravenous (IV) CEP-18770 on days 1, 8, and 15, oral lenalidomide on days 1 through 21, and oral dexamethasone on days 1, 8, 15, and 22 of each 28-day cycle. Treatment with all 3 drugs will continue for up to 12 cycles (approximately 11 months), or until disease progression or intolerable toxicities. Patients experiencing clinical benefit may continue to receive additional treatment at the investigator's discretion and following sponsor notification. In part 2 of the study, patients will receive CEP-18770 as a slow IV bolus (approximately 1 milliliter per minute) at the maximum tolerated dose on days 1, 8, and 15 of every 28-day cycle. Patients who complete or discontinue study drug treatment and whose disease has not progressed will have study visits every 7-9 weeks during follow-up until disease progression, death, or until they have been monitored for 1 year after the first administration of study drug, whichever occurs first.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient is a man or woman at least 18 years of age with documented multiple myeloma.
  • The patient has relapsed or progressive disease after receiving at least 1 previous chemotherapy treatment but no more than 5 previous therapies.
  • The patient has measurable disease defined as 1 of the following:

    • serum M-protein 0.5 g/dL or greater
    • urine M-protein 200 mg/24 hours or greater
  • The patient has a life expectancy of more than 3 months.
  • Written informed consent is obtained.
  • The patient has an ECOG performance status of 0, 1, or 2.
  • The patient has adequate hepatic and renal function and hematologic assessments as specified by the study protocol
  • The patient has been independent of support with granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF) for more than 1 week at the time of screening.
  • The patient has been independent of platelet transfusions for 1 week at the time of screening.
  • The patient may have received an allogeneic and/or autologous transplant.
  • The patient must agree to register into the mandatory risk evaluation and mitigation program for receiving lenalidomide if required by local regulations.
  • Agreement by women of childbearing potential (not surgically sterile or 24 months postmenopausal) to use 2 medically accepted methods of contraception and must agree to continue use of these methods from 4 weeks prior to treatment to 4 weeks after treatment. Acceptable methods of contraception include at least one highly effective method (e.g., intrauterine device [IUD], non-combination hormonal contraception, tubal ligation, or partner's vasectomy) and one additional method (e.g., latex condom, diaphragm, or cervical cap).
  • Agreement by men who are sexually active with a woman of childbearing potential (as defined in the criterion above), to use a condom during any sexual contact for the duration of the study and for 4 weeks after the last administration of study drug. This requirement applies even if the man has had a vasectomy.
  • The patient may not donate blood, semen or sperm while taking lenalidomide or for 4 weeks after the last administration of lenalidomide.
  • The patient may not breastfeed while taking lenalidomide or for 4 weeks after the last administration of lenalidomide.

Exclusion Criteria:

  • The patient has nonmeasurable multiple myeloma, defined as less than 0.5 g/dL M-protein in the serum, and less than 200 mg/24 hours M-protein in the urine.
  • The patient could not tolerate previous lenalidomide or low-dose dexamethasone treatment.
  • The patient had previous treatment with CEP-18770.
  • 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]).
  • The patient has plasma cell leukemia or primary amyloidosis.
  • The patient received chemotherapy with approved or investigative anticancer therapeutics within 3 weeks before the first dose of study drug.
  • The patient received radiation therapy or immunotherapy within 4 weeks or localized radiation therapy within 1 week prior to the first dose of study drug.
  • The patient had major surgery within 3 weeks before the first dose of study drug.
  • 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.
  • The patient had an acute infection requiring systemic antibiotics, antiviral agents, or antifungal agents within 2 weeks before the first dose of study drug.
  • The patient has a known or suspected human immunodeficiency virus (HIV) infection, acute or chronic hepatitis B virus or hepatitis C virus on the basis of their medical history.
  • The patient has myelodysplastic or myeloproliferative syndrome.
  • The patient has significant neuropathy (at least grade 2, or grade 1 with pain).
  • The patient is a pregnant or lactating woman.
  • The patient has known hypersensitivity to CEP-18770, lenalidomide, thalidomide, dexamethasone, mannitol, or hydroxypropyl betadex.
  • 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.
  • The patient has a history of malignancy, other than multiple myeloma, within the last 5 years excluding adequately treated curable disease or indolent disease that is not likely to require therapy during the conduct of the study.
  • The patient has known central nervous system (CNS) involvement.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01348919

Locations
United States, Georgia
Teva Investigational Site 1
Augusta, Georgia, United States
United States, Kentucky
Teva Investigational Site 3
Lexington, Kentucky, United States
United States, Texas
Teva Investigational Site 2
Houston, Texas, United States
New Zealand
Teva Investigational Site 204
Auckland, New Zealand
Teva Investigational Site 201
Auckland, New Zealand
Teva Investigational Site 200
Christchurch, New Zealand
Teva Investigational Site 206
Hamilton, New Zealand
Teva Investigational Site 205
Newtown, New Zealand
Teva Investigational Site 202
Palmerston North, New Zealand
Teva Investigational Site 203
Takapuna, New Zealand
Sponsors and Collaborators
Cephalon
Investigators
Study Director: Sponsor's Medical Expert, Medical Director - Clinical Research Oncology Cephalon
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier: NCT01348919     History of Changes
Other Study ID Numbers: C18770/2049, 2010-020910-27
Study First Received: May 4, 2011
Last Updated: August 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Teva Pharmaceutical Industries:
Cancer
Multiple myeloma
CEP-18770
Lenalidomide
Dexamethasone

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Delanzomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents

ClinicalTrials.gov processed this record on October 21, 2014