Dovitinib Combined With Bortezomib and Dexamethasone for Relapsed/Refractory Multiple Myeloma

NCT01680796 | Withdrawn Phase 1 DMC

• 1 other identifier: CTKI258AU012T
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label phase I study in which dovitinib is given in combination with bortezomib and dexamethasone. Dovitinib dose escalation is planned in order to determine its maximum tolerated dose when given in this combination.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Relapsed Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety and dose-limiting toxicity of treatment with dovitinib in combination with bortezomib/ dexamethasone.

  Determination of the maximum tolerated dose of dovitinib will be based on Treatment Cycle 1 safety data for all subjects for whom all safety assessments during Treatment Cycle 1, as well as the pre-dosing safety assessments performed on Study Day 1 of Treatment Cycle 2, are completed and who do not receive alternate anti-neoplastic therapies during that period.

  Treatment Cycle 1 (three weeks) for each participant.

Secondary Outcomes (1)

• To assess the overall response rate for the combination dovitinib/bortezomib/ dexamethasone in patients receiving at least 4 cycles of therapy.

  Participants will be followed for up to one year.

Other Outcomes (1)

• Other Secondary Efficacy Objectives

  Up to 10 years

Study Arms (1)

Active Treatment

EXPERIMENTAL

Dovitinib will be given at up to four different dose levels beginning with dose level 1 on a 5 days on/2 days off dosing schedule of each 21-day cycle. Bortezomib will be given at two different dose levels intravenously on Days 1 and 8 of each 21-day cycle. Dexamethasone will be given orally on Days 1, 2, 8, and 9 of each 21-day cycle.

Drug: Dovitinib; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Dovitinib DRUG

Dose Level 0: 200 mg daily Dose Level 1: 300 mg daily Dose Level 2: 300 mg daily Dose Level 3: 400 mg daily Dose Level 4: 500 mg daily

Also known as: TKI258

Active Treatment

Bortezomib DRUG

Dose Level 0: 1.3 mg/m2 IV on days 1 and 8 Dose Level 1: 1.3 mg/m2 IV on days 1 and 8 Dose Level 2: 1.6 mg/m2 IV on days 1 and 8 Dose Level 3: 1.6 mg/m2 IV on days 1 and 8 Dose Level 4: 1.6 mg/m2 IV on days 1 and 8

Also known as: Velcade

Active Treatment

Dexamethasone DRUG

Dexamethasone 20 mg will be given orally on Days 1, 2, 8, and 9 of each 21-day cycle.

Also known as: Decadron

Active Treatment

Eligibility Criteria

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

You may qualify if:

• Diagnosis of multiple myeloma
• Karnofsky performance status ≥ 70
• Age ≥ 18 years old
• Evidence of relapsed or refractory disease as documented from the prior treatment history
• Have received at least 1, but not more than 3, prior treatment regimens for multiple myeloma including chemotherapy, autologous stem cell transplantation, immunotherapy, or other investigational agents. Prior allogeneic stem cell transplant and prior therapy with bortezomib (with no evidence of disease resistance to bortezomib) are permitted.
• Last dose of chemotherapy no less than 4 weeks prior to receipt of study medication and have recovered from the side effects of such therapy
• Last dose of biological therapy, or antibody, or other investigational agents, no less than 4 weeks prior to receipt of study medication
• Subjects must have the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin (Hgb) \> 9 g/dL
• Serum total bilirubin: ≤ 1.5 x ULN
• ALT and AST ≤ 3.0 x ULN
• Serum creatinine ≤ 1.5 x ULN
• Willing and able to undergo bone marrow aspirates as per protocol, with/without bone marrow biopsy according to the study center's practice. - Life expectancy of ≥ 12 weeks

You may not qualify if:

• Subjects with CNS (central nervous system) disease
• Subjects with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, or skin cancer
• Subjects who have received the last administration of an anticancer therapy including chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosurea, mitomycin-C, targeted therapy and radiation) ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
• Subjects who have had radiotherapy ≤ 4 weeks prior to starting study drug, or ≤ 2 weeks prior to starting study drug in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities
• Subjects who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or subjects who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
• Subjects with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• History or presence of serious uncontrolled ventricular arrhythmias
• Clinically significant resting bradycardia
• LVEF assessed by 2-D echocardiogram (ECHO) \< 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA) \< 45% or lower limit of normal (whichever is higher).
• Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)
• Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s),
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection),
• Cirrhosis, chronic active hepatitis or chronic persistent hepatitis,
• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory),

Sponsors & Collaborators

• University of Florida: lead
• Novartis Pharmaceuticals: collaborator

MeSH Terms

Conditions

Multiple Myeloma

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Bortezomib; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; 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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Jan S. Moreb, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2012
• First Posted: September 7, 2012
• Study Start: February 1, 2013
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: February 20, 2013

Record last verified: 2013-02