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

NCT01348919 | Completed Phase 1 Results

• 2 other identifiers: C18770/20492010-020910-27
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 8

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

Cancer; Multiple myeloma; CEP-18770; Lenalidomide; Dexamethasone

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR) in Participants Treated at the (Maximum Tolerated Dose) MTD, as Assessed Using International Myeloma Working Group (IMWG) Criteria

  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

  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 Outcomes (6)

• Duration of Response (DOR) for Participants Treated With CEP-18770 at the MTD, as Assessed Using IMWG Criteria

  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

  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)

  From the first administration of CEP-18770 up to approximately 1.5 years

• Maximum Observed Plasma Concentration (Cmax) of CEP-18770

  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

  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

Study Arms (3)

CEP-18770 Dose A

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone

CEP-18770 Dose B

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone

CEP-18770 Dose C

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

CEP-18770 DRUG

CEP-18770 will be administered per dose and schedule specified in the arm description.

Also known as: Delanzomib

CEP-18770 Dose A; CEP-18770 Dose B; CEP-18770 Dose C

Lenalidomide DRUG

Lenalidomide will be administered per dose and schedule specified in the arm description.

CEP-18770 Dose A; CEP-18770 Dose B; CEP-18770 Dose C

Dexamethasone DRUG

Dexamethasone will be administered per dose and schedule specified in the arm description.

CEP-18770 Dose A; CEP-18770 Dose B; CEP-18770 Dose C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (8)

Teva Investigational Site 1

Augusta, Georgia, 30912, United States

Location

Teva Investigational Site 3

Lexington, Kentucky, 40536, United States

Location

Teva Investigational Site 2

Houston, Texas, 77030, United States

Location

Teva Investigational Site 201

Auckland, 1640, New Zealand

Location

Teva Investigational Site 204

Auckland, 92024, New Zealand

Location

Teva Investigational Site 200

Christchurch, 8011, New Zealand

Location

Teva Investigational Site 206

Hamilton, 3204, New Zealand

Location

Teva Investigational Site 205

Newtown, 6021, New Zealand

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms

Interventions

delanzomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products R&D, Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Teva Medical Expert

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2011
• First Posted: May 6, 2011
• Study Start: August 3, 2011
• Primary Completion: March 14, 2013
• Study Completion: March 14, 2013
• Last Updated: June 28, 2023
• Results First Posted: June 28, 2023

Record last verified: 2023-05

Locations

US (3); NZ (5)