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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by HealthCare Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
HealthCare Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01711671
First received: October 18, 2012
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Multiple Myeloma
Drug: DKN-01 300 mg
Drug: DKN-01 600 mg
Drug: Standard of Care
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of DKN-01 and Lenalidomide (Revlimid®)/Dexamethasone Versus Lenalidomide/Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by HealthCare Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Fluorine F18 sodium fluoride positron emission tomography (NaF-PET/CT) standard uptake value (SUV) [ Time Frame: Pre-study to after 6 months of therapy ] [ Designated as safety issue: No ]
    SUV as measured by NaF-PET/CT in both myeloma bone lesions and normal bone

  • Fluorine F18 sodium fluoride positron emission tomography (NaF-PET/CT) influx constant (Ki) [ Time Frame: Pre-study to after 6 months of therapy ] [ Designated as safety issue: No ]
    Ki as measured by NaF-PET/CT in both myeloma bone lesions and normal bone

  • F18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) standard uptake value (SUV) [ Time Frame: Pre-study to after 6 months of therapy ] [ Designated as safety issue: No ]
    SUV as measured by FDG-PET/CT in both myeloma bone lesions and normal bone

  • Number of patients with treatment emergent adverse events [ Time Frame: Baseline to study completion (approximately 7 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: Baseline to study completion (approximately 7 months) ] [ Designated as safety issue: No ]
  • Progression free survival (PFS) [ Time Frame: Baseline to study completion (approximately 7 months) ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Baseline to study completion (approximately 7 months) ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Baseline to study completion (approximately 7 months) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: area under the concentration - time curve (AUC) of a single dose of DKN-01 [ Time Frame: Dosing interval of 2 weeks following the first dose in Cycle 1 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: maximum plasma concentration (Cmax) of a single dose of DKN-01 [ Time Frame: Dosing interval of 2 weeks following the first dose in Cycle 1 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: trough DKN-01 concentrations on Cycle 2 and Cycle 3 [ Time Frame: Cycle 2 Day 1 Pre-dose, Cycle 3 Day 1 Pre-dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: May 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DKN-01 300mg
DKN-01 plus lenalidomide (Revlimid)/dexamethasone
Drug: DKN-01 300 mg
300 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone
Experimental: DKN-01 600mg
DKN-01 plus lenalidomide (Revlimid)/dexamethasone
Drug: DKN-01 600 mg
600 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone
Active Comparator: Standard of Care
Lenalidomide (Revlimid)/dexamethasone
Drug: Standard of Care
Current approved standard of care
Other Names:
  • Lenalidomide
  • Revlimid
  • Dexamethasone

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed or refractory Multiple Myeloma (MM)

    a. Treated with at least 1 prior regimen for myeloma

    1. Prior treatment with bortezomib (Velcade) is acceptable with a wash-out of 2 weeks
    2. Treatment with prior autologous transplant is permitted
    3. 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) :

    1. Second line or greater/Refractory/Relapsed, Stage I, Stage II, Stage III
    2. 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:

    1. Hematologic:

      1. Absolute neutrophil count (ANC) greater than or equal to (≥) 1000/microliter
      2. Platelet (PLT) count ≥ 75,000/microliter
      3. Hemoglobin (Hgb) ≥ 8.0 g/dL
    2. Acceptable coagulation status:

      1. Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.2 x the upper limit of normal (ULN) unless receiving anticoagulation therapy. If receiving anticoagulation therapy, eligibility will be based upon International Normalization Ratio (INR)
      2. International normalized ratio (INR) less than or equal to (≤) 1.6 (unless receiving anticoagulation therapy)

        • If receiving warfarin: INR ≤ 3.0 (and no active bleeding, [i.e., no bleeding within 14 days prior to first dose of study therapy])
    3. Hepatic:

      1. Bilirubin ≤ 1.5 x ULN
      2. Alanine Transaminase (ALT) and Aspartate Transaminase (AST) ≤ 2.5 x ULN (if liver metastases are present, then ≤ 5 x ULN is allowed)
    4. Renal:

      1. Calculated creatinine clearance ≥ 45 mL using the Cockcroft and Gault Method
  • Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 10 to 14 days and again within 24 hours of starting study drug

    1. WCBP must agree to have pregnancy tests monthly (every 14 days for women with irregular cycles) while on study drug and 4 weeks after the last dose of study drug
    2. Men must also agree to use a condom if their partner is of child bearing potential, even if they have had a successful vasectomy
    3. Males and females with reproductive potential must agree to use medically approved contraceptive precautions starting 4 weeks prior to initiation of the therapy and during the trial and for 18 months following the last dose of study drug
    4. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Provide written informed consent prior to any study-specific procedures
  • Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

Exclusion Criteria:

  • 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
  • History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are considered clinically significant or may have an impact on the interpretation of the scan. Degenerative changes of the hip joint are not exclusionary
  • 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)
  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: NCT01711671

Contacts
Contact: Diana Todd Diana.Todd@TheoremClinical.com

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Jacob Laubach, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Andrew Yee, MD         
Sponsors and Collaborators
HealthCare Pharmaceuticals, Inc.
Investigators
Study Director: Diana Todd Theorem Clinical Research
  More Information

No publications provided

Responsible Party: HealthCare Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01711671     History of Changes
Other Study ID Numbers: DEK-DKK1-P101, DKN-01, LY2812176
Study First Received: October 18, 2012
Last Updated: June 26, 2014
Health Authority: United States: Food and Drug Administration

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
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
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 22, 2014