A Study of DKN-01 and Lenalidomide/Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

NCT01711671 | Completed Phase 1

• 3 other identifiers: DEK-DKK1-P101DKN-01LY2812176
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

A study to evaluate the safety, efficacy and bone changes with combination therapy of intravenous (IV) infused DKN-01 and lenalidomide/dexamethasone, versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma (MM) patients

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• Fluorine F18 sodium fluoride positron emission tomography (NaF-PET/CT) standard uptake value (SUV)

  SUV as measured by NaF-PET/CT in both myeloma bone lesions and normal bone

  Pre-study to after 6 months of therapy

• Fluorine F18 sodium fluoride positron emission tomography (NaF-PET/CT) influx constant (Ki)

  Ki as measured by NaF-PET/CT in both myeloma bone lesions and normal bone

  Pre-study to after 6 months of therapy

• F18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) standard uptake value (SUV)

  SUV as measured by FDG-PET/CT in both myeloma bone lesions and normal bone

  Pre-study to after 6 months of therapy

• Number of patients with treatment emergent adverse events

  Baseline to study completion (approximately 7 months)

Secondary Outcomes (7)

• Overall response rate (ORR)

  Baseline to study completion (approximately 7 months)

• Progression free survival (PFS)

  Baseline to study completion (approximately 7 months)

• Duration of response

  Baseline to study completion (approximately 7 months)

• Overall survival

  Baseline to study completion (approximately 7 months)

• Pharmacokinetics: area under the concentration - time curve (AUC) of a single dose of DKN-01

  Dosing interval of 2 weeks following the first dose in Cycle 1

Study Arms (3)

DKN-01 300mg

EXPERIMENTAL

DKN-01 plus lenalidomide (Revlimid)/dexamethasone

Drug: DKN-01 300 mg

DKN-01 600mg

EXPERIMENTAL

DKN-01 plus lenalidomide (Revlimid)/dexamethasone

Drug: DKN-01 600 mg

Standard of Care

ACTIVE COMPARATOR

Lenalidomide (Revlimid)/dexamethasone

Drug: Standard of Care

Interventions

DKN-01 300 mg DRUG

300 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone

DKN-01 300mg

DKN-01 600 mg DRUG

600 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone

DKN-01 600mg

Standard of Care DRUG

Current approved standard of care

Also known as: Lenalidomide, Revlimid, Dexamethasone

Standard of Care

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed or refractory Multiple Myeloma (MM)
• a. Treated with at least 1 prior regimen for myeloma
• Prior treatment with bortezomib (Velcade) is acceptable with a wash-out of 2 weeks
• Treatment with prior autologous transplant is permitted
• If a transplant is used as consolidation following chemotherapy, without intervening disease progression, it will be considered 1 line of treatment with the preceding chemotherapy
• Diagnosis of symptomatic MM as defined by the International Myeloma Working Group (IMWG) :
• Second line or greater/Refractory/Relapsed, Stage I, Stage II, Stage III
• Measureable disease as indicated by monoclonal protein in the serum of greater than or equal to (≥) 1 grams per deciliter (g/dL), involved serum free light chain assay ≥10 mg/dL (≥100 mg/L) provided the serum free light chain ratio is abnormal; monoclonal light chain in the urine protein electrophoresis of ≥ 200 mg/24 hours, or measurable plasmacytoma
• At least 1 osteolytic bone lesion
• Disease-free of active second/secondary or prior malignancies for equal to or over 5 years with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the cervix or breast
• Ambulatory patients greater than or equal to (≥) 30 years of age
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Estimated life expectancy of ≥ 26 weeks
• Adequate organ function including:
• Hematologic:

You may not qualify if:

• Received treatment with an investigational drug, which has not received regulatory approval for any indication, within 28 days of study treatment with DKN-01
• Received any experimental non-drug therapy (e.g., donor leukocyte/mononuclear cell infusions) within 56 days of entry
• Previously treated with an anti-Dickkopf-1 (anti-DKK-1) or antibody therapy, or have had a significant allergy to a known pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the patient
• Received radiation therapy, surgery, or chemotherapy within 2 weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C)
• Received bisphosphonates (e.g., etidronate, clodronate, tiludronate, pamidronate, neridronate, olpadronate, alendronate, ibandronate, risedronate, zoledronate) within 2 weeks prior to study entry
• Symptomatic central nervous system (CNS) malignancy or metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic patients without a history of CNS metastases is not required
• Have a history of major organ transplant (for example: heart, lungs, liver, and kidney)
• Are pregnant or nursing
• Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb)
• Active, uncontrolled bacterial, viral, or fungal infections, including urinary tract infection, within 7 days of study entry requiring systemic therapy
• Serious cardiac condition such as myocardial infarction within the past 6 months, unstable angina, or Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA); have ECG abnormalities including baseline 12-lead ECG with Fridericia-corrected QT interval (QTcF) \> 470 msec (female) or \> 450 msec (male), a history of congenital long QT syndrome, or any ECG abnormality that, in the opinion of the Investigator, would preclude safe participation in the study
• Known concomitant disease(s) known to influence calcium metabolism including hyperparathyroidism, hyperthyroidism, Paget's disease of bone, or any other concurrent severe or uncontrolled concomitant medical condition that, in the opinion of the Investigator, would preclude participation in this study
• Patients who are currently receiving lithium chloride (LiCl)

Sponsors & Collaborators

• Leap Therapeutics, Inc.: lead

Study Sites (3)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Standard of Care; Lenalidomide; Dexamethasone

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)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; 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

Study Officials

• Cynthia Sirard

  Leap Therapeutics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 18, 2012
• First Posted: October 22, 2012
• Study Start: May 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: August 3, 2025

Record last verified: 2025-07

Locations

US (3)