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

June 6, 2023 updated by: Teva Branded Pharmaceutical Products R&D, Inc.

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 participant 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. Participants 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. Participants experiencing clinical benefit may continue to receive additional treatment at the investigator's discretion and following sponsor notification. In part 2 of the study, participants 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. Participants 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • New Zealand
      • Auckland, New Zealand, 1640
        • Teva Investigational Site 201
      • Auckland, New Zealand, 92024
        • Teva Investigational Site 204
      • Christchurch, New Zealand, 8011
        • Teva Investigational Site 200
      • Hamilton, New Zealand, 3204
        • Teva Investigational Site 206
      • Newtown, New Zealand, 6021
        • Teva Investigational Site 205
  • United States
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Teva Investigational Site 1
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Teva Investigational Site 3
    • Texas
      • Houston, Texas, United States, 77030
        • Teva Investigational Site 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • The participant is a man or woman at least 18 years of age with documented multiple myeloma.
  • The participant has relapsed or progressive disease after receiving at least 1 previous chemotherapy treatment but no more than 5 previous therapies.
  • The participant has measurable disease defined as 1 of the following:
  • serum M-protein 0.5 grams (g)/deciliter (dL) or greater
  • urine M-protein 200 mg/24 hours or greater
  • The participant has a life expectancy of more than 3 months.
  • Written informed consent is obtained.
  • The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • The participant has adequate hepatic and renal function and hematologic assessments as specified by the study protocol
  • The participant 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 participant has been independent of platelet transfusions for 1 week at the time of screening.
  • The participant may have received an allogeneic and/or autologous transplant.
  • The participant 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 (for example, intrauterine device [IUD], non-combination hormonal contraception, tubal ligation, or partner's vasectomy) and one additional method (for example, 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 participant may not donate blood, semen or sperm while taking lenalidomide or for 4 weeks after the last administration of lenalidomide.
  • The participant may not breastfeed while taking lenalidomide or for 4 weeks after the last administration of lenalidomide.

Exclusion Criteria:

  • The participant 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 participant could not tolerate previous lenalidomide or low-dose dexamethasone treatment.
  • The participant had previous treatment with CEP-18770.
  • The participant 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 participant has plasma cell leukemia or primary amyloidosis.
  • The participant received chemotherapy with approved or investigative anticancer therapeutics within 3 weeks before the first dose of study drug.
  • The participant received radiation therapy or immunotherapy within 4 weeks or localized radiation therapy within 1 week prior to the first dose of study drug.
  • The participant had major surgery within 3 weeks before the first dose of study drug.
  • The participant 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 participant had an acute infection requiring systemic antibiotics, antiviral agents, or antifungal agents within 2 weeks before the first dose of study drug.
  • The participant 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 participant has myelodysplastic or myeloproliferative syndrome.
  • The participant has significant neuropathy (at least grade 2, or grade 1 with pain).
  • The participant is a pregnant or lactating woman.
  • The participant has known hypersensitivity to CEP-18770, lenalidomide, thalidomide, dexamethasone, mannitol, or hydroxypropyl betadex.
  • The participant received glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last 2 weeks prior to the first dose of study drug.
  • The participant 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 participant has known central nervous system (CNS) involvement.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CEP-18770 Dose A
Participants will receive CEP-18770 Dose A intravenously (IV) on Days 1, 8, and 15 in each 28-day cycle. In addition, participants will receive a fixed dose of 25 mg oral lenalidomide on Days 1 through 21 and a fixed dose of 40 mg oral dexamethasone on Days 1, 8, 15, and 22 of each 28-day cycle.
Drug: CEP-18770
CEP-18770 will be administered per dose and schedule specified in the arm description.
Other Names:
  • Delanzomib
Drug: Lenalidomide
Lenalidomide will be administered per dose and schedule specified in the arm description.
Drug: Dexamethasone
Dexamethasone will be administered per dose and schedule specified in the arm description.
Experimental: CEP-18770 Dose B
Participants will receive CEP-18770 Dose B IV on Days 1, 8, and 15 in each 28-day cycle. In addition, participants will receive a fixed dose of 25 mg oral lenalidomide on Days 1 through 21 and a fixed dose of 40 mg oral dexamethasone on Days 1, 8, 15, and 22 of each 28-day cycle.
Drug: CEP-18770
CEP-18770 will be administered per dose and schedule specified in the arm description.
Other Names:
  • Delanzomib
Drug: Lenalidomide
Lenalidomide will be administered per dose and schedule specified in the arm description.
Drug: Dexamethasone
Dexamethasone will be administered per dose and schedule specified in the arm description.
Experimental: CEP-18770 Dose C
Participants will receive CEP-18770 Dose C IV on Days 1, 8, and 15 in each 28-day cycle. In addition, participants will receive a fixed dose of 25 mg oral lenalidomide on Days 1 through 21 and a fixed dose of 40 mg oral dexamethasone on Days 1, 8, 15, and 22 of each 28-day cycle.
Drug: CEP-18770
CEP-18770 will be administered per dose and schedule specified in the arm description.
Other Names:
  • Delanzomib
Drug: Lenalidomide
Lenalidomide will be administered per dose and schedule specified in the arm description.
Drug: Dexamethasone
Dexamethasone will be administered per dose and schedule specified in the arm description.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) in Participants Treated at the (Maximum Tolerated Dose) MTD, as Assessed Using International Myeloma Working Group (IMWG) Criteria
Time Frame: From the first administration of CEP-18770 up to approximately 1.5 years
The ORR is defined as percentage of participants who achieve a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) during the study. sCR: negative immunofixation in serum and urine; disappearance of any soft tissue plasmacytomas; < 5% plasma cells in bone marrow; normal free light chain (FLC) ratio; and absence of clonal cells in bone marrow. CR: negative immunofixation in serum and urine; disappearance of any soft tissue plasmacytomas; and <5% plasma cells in bone marrow. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis; 90% or greater reduction in serum M-protein level and urine M-protein level less than 100 milligrams (mg)/24 hours. PR: ≥50% reduction in serum M-protein level; ≥90% reduction in 24-hour urinary M-protein level or reduction to less than 200 mg per 24 hours; and ≥50% reduction in the size of any soft tissue plasmacytomas present at baseline.
From the first administration of CEP-18770 up to approximately 1.5 years
Maximum Tolerated Dose of CEP-18770
Time Frame: Cycle 1 (28 days)
MTD was based on the assessment of dose-limiting toxicity (DLT) during cycle 1 only and was defined as the highest dose at which fewer than one-third of participants in a cohort experience DLT. A DLT was defined as any of the following drug-related toxicities occurring during Cycle 1: Hematologic adverse events (AEs) (Grade 4 hematologic AEs, Grade 3 hematologic AEs with sequelae); Grade 3 nonhematologic AEs; Neuropathy (Grade 2 neuropathy, Grade 1 neuropathy with pain, worsening grade of neuropathy or new symptoms of pain associated with neuropathy); Any other toxicity that, in the judgment of the principal investigator, was a DLT; If a participant cannot receive 75% of the planned dose for any of the 3 agents (missing >1 dose of CEP-18770, or >5 doses of lenalidomide, or >1 dose of dexamethasone [either consecutively or separately]), due to a drug-related AE, the event was considered a DLT, even if the grade of toxicity was lower than specified DLT determination as described above.
Cycle 1 (28 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax) of CEP-18770
Time Frame: Before and immediately after end of infusion (EOI) and at approximately 2, 4, and 8 hours after the EOI on Days 1 and 15 of Cycle 1
Before and immediately after end of infusion (EOI) and at approximately 2, 4, and 8 hours after the EOI on Days 1 and 15 of Cycle 1
Time to Reach Cmax (Tmax) of CEP-18770
Time Frame: Before and immediately after end of infusion (EOI) and at approximately 2, 4, and 8 hours after the EOI on Days 1 and 15 of Cycle 1
Before and immediately after end of infusion (EOI) and at approximately 2, 4, and 8 hours after the EOI on Days 1 and 15 of Cycle 1
Area Under the Plasma Concentration-Time Curve From Time 0 to t (AUC0-t) of CEP-18770
Time Frame: Before and immediately after end of infusion (EOI) and at approximately 2, 4, and 8 hours after the EOI on Days 1 and 15 of Cycle 1
Before and immediately after end of infusion (EOI) and at approximately 2, 4, and 8 hours after the EOI on Days 1 and 15 of Cycle 1
Duration of Response (DOR) for Participants Treated With CEP-18770 at the MTD, as Assessed Using IMWG Criteria
Time Frame: From the date of first response to the date of disease progression (up to approximately 1.5 years)
DOR was defined as the time interval from the date of first response (sCR, CR, VGPR, or PR) to the date of disease progression. sCR, CR, VGPR, and PR as defined in outcome measure 1. Disease progression was defined as any 1 or more of the following: Increase of 25% or more from lowest response level in any 1 or more of the following: - serum M-component (absolute increase must be ≥0.5 grams [g]/deciliter [dL]), - urine M-component (absolute increase must be ≥200 mg/24 hours), bone marrow plasma cell percentage ≥10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; and development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that could be attributed solely to the plasma cell proliferation disorder.
From the date of first response to the date of disease progression (up to approximately 1.5 years)
Time to Progression (TTP) for Participants Treated With CEP-18770 at the MTD, as Assessed Using IMWG Criteria
Time Frame: From the date of first dose of study drug to the date of disease progression (up to approximately 1.5 years)
TTP was defined as the time interval from the date of first dose to the date of disease progression. Disease progression was defined as any 1 or more of the following: Increase of 25% or more from lowest response level in any 1 or more of the following: - serum M-component (absolute increase must be ≥0.5 g/dL), - urine M-component (absolute increase must be ≥200 mg/24 hours), bone marrow plasma cell percentage ≥10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; and development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that could be attributed solely to the plasma cell proliferation disorder.
From the date of first dose of study drug to the date of disease progression (up to approximately 1.5 years)
Number of Participants With Adverse Events (AEs)
Time Frame: From the first administration of CEP-18770 up to approximately 1.5 years
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
From the first administration of CEP-18770 up to approximately 1.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Teva Medical Expert, Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 3, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 14, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 14, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 4, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2011

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 6, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 28, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 6, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • C18770/2049
  • 2010-020910-27 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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