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Study of Melflufen + Dex With Bortezomib or Daratumumab in Patients With RRMM (ANCHOR)

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ClinicalTrials.gov Identifier: NCT03481556
Recruitment Status : Recruiting
First Posted : March 29, 2018
Last Update Posted : March 21, 2019
Sponsor:
Information provided by (Responsible Party):
Oncopeptides AB

Brief Summary:
This is an open-label Phase 1/2a study which will enroll patients that have relapsed or relapsed-refractory multiple myeloma following 1-4 lines of prior therapy. Patients will receive either melflufen+dexamethasone+bortezomib or melflufen+dexamethasone+daratumumab and are required to be PI refractory to be enrolled to the bortezomib regimen, and to not have any prior exposure to daratumumab or other antiCD-38 mAb to be enrolled to the daratumumab regimen.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Melflufen Drug: Dexamethasone Drug: Bortezomib Drug: Daratumumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Phase 1/2a Study of the Safety and Efficacy of Melflufen and Dexamethasone in Combination With Either Bortezomib or Daratumumab in Patients With Relapsed or Relapsed-Refractory Multiple Myeloma
Actual Study Start Date : April 16, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: A (melflufen+bortezomib+dex)
Melflufen 30 mg and 40 mg or 20 mg i.v. Day 1 of each 28-day cycle in combination with bortezomib at 1.3mg/m² S.Q. on Days 1, 4, 8, 11 and dexamethasone 20 mg (12 mg ≥ 75 years) Days 1, 4, 8, 11 and 40 mg (20 mg ≥ 75 years) on Day 15 and 22 of each 28-day cycle.
Drug: Melflufen
Intravenous infusion

Drug: Dexamethasone
Oral tablets
Other Names:
  • Dex
  • Fortecortin
  • Decadron

Drug: Bortezomib
Subcutaneous administration
Other Name: Velcade

Experimental: B (melflufen+daratumumab+dex)
Melflufen 30 mg and 40 mg or 20 mg i.v. Day 1 of each 28-day cycle in combination with daratumumab 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks until PD. Dexamethasone will be given day of and after daratumumab infusions, 20 mg i.v. pre daratumumab and 20 mg p.o. day after daratumumab (20 mg total for ≥ 75 years).
Drug: Melflufen
Intravenous infusion

Drug: Dexamethasone
Oral tablets
Other Names:
  • Dex
  • Fortecortin
  • Decadron

Drug: Daratumumab
Intravenous infusion
Other Names:
  • Dara
  • Darzalex




Primary Outcome Measures :
  1. Phase 1: The primary endpoint of Phase 1 is to monitor and analyze the frequency and grade of AEs occurring during Cycle 1 at each dose level to be tested. Each Regimen to be evaluated separately. [ Time Frame: During first cycle (28 days) of each cohort ]
    Dose-limiting toxicity to determine the optimal dose of melflufen, up to a maximum of 40 mg, given every 28 days in triple drug combination therapy

  2. Phase 2: The proportion of efficacy evaluable patients in each Regimen who achieve a confirmed sCR, CR, VGPR, or PR as their best response. Each Regimen to be evaluated separately. [ Time Frame: From start of treatment until best response achieved before confirmed progression. For an average patient this is achieved within 6 months. ]
    Investigators assessment of response according to IMWG criteria


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: From start of treatment until best response achieved before confirmed progression. For an average patient this is achieved within 6 months. ]
    To evaluate overall response rate according to IMWG, including CR, VGPR and PR.

  2. Duration of Response (DOR) [ Time Frame: From first evidence of response until confirmed progression, to be assessed up to 24 months ]
    To assess the DOR

  3. Time to Response (TTR) [ Time Frame: From start of dosing until time of response. For an average patient this is achieved within 6 months. ]
    To assess the TTR

  4. Progression-Free Survival (PFS) [ Time Frame: From start of dosing until confirmed progression, to be assessed up to 24 months ]
    To assess the PFS

  5. Overall Survival (OS) [ Time Frame: From start of dosing until end of study (2 years after confirmed progression) ]
    To assess the OS data

  6. Incidence of Treatment-Emergent Adverse Events [ Time Frame: From start of dosing until 30 days after last dose, to be assessed up to 24 months ]
    To assess the safety and tolerability through AE reporting following CTCAE v4



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, age 18 years or older
  2. A prior diagnosis of multiple myeloma with documented disease progression in need of treatment at time of screening
  3. One to four prior lines of therapy
  4. Measurable disease defined as any of the following:

    • Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP)
    • ≥ 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP)
    • Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio
  5. Life expectancy of ≥ 6 months
  6. ECOG performance status ≤ 2. (Patients with lower performance status based solely on bone pain secondary to multiple myeloma may be eligible following consultation and approval of the medical monitor)
  7. Patient is a female of childbearing potential (FCBP)* with a negative serum or urine pregnancy test prior to initiation of therapy and agrees to practice appropriate methods of birth control, or the patient is male and agrees to practice appropriate methods of birth control
  8. Ability to understand the purpose and risks of the study and provide signed and dated informed consent
  9. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec
  10. Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before study drug administration on Cycle 1 Day 1:

    • Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109/L) (Growth factors cannot be used within 10 days (14 days for pegfilgrastim) prior to initiation of therapy)
    • Platelet count ≥ 75,000 cells/mm3 (75 x 109/L) (without required transfusions during the 10 days prior to initiation of therapy)
    • Hemoglobin ≥ 8.0 g/dl (red blood cell (RBC) transfusions are permitted)
    • Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), or patients diagnosed with Gilbert's syndrome, that have been reviewed and approved by the medical monitor
    • AST/SGOT and ALT/SGPT ≤ 3.0 x ULN
    • Renal function: Estimated creatinine clearance by Cockcroft-Gault formula ≥ 45 mL/min and serum creatinine ≤ 2 mg/dL
  11. Must have, or be willing to have an acceptable central catheter. (Port a cath, peripherally inserted central catheter [PICC] line, or central venous catheter)

    • (FCBP) is any sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (not having menstrual cycles due to cancer therapy does not rule out childbearing potential) for at least 24 consecutive months.

Exclusion Criteria:

  1. Primary refractory disease (i.e. never responded with ≥ MR to any prior therapy)
  2. Evidence of mucosal or internal bleeding and/or are platelet transfusion refractory (i.e. platelet count fails to increase by > 10,000 cells/mm3 after transfusion of an appropriate dose of platelets)
  3. Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study. Examples of such conditions are: a significant history of cardiovascular disease (e.g., myocardial infarction, significant conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months)
  4. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of therapy
  5. Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance
  6. Pregnant or breast-feeding females
  7. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
  8. Known human immunodeficiency virus or active hepatitis B or C viral infection
  9. Concurrent symptomatic amyloidosis or plasma cell leukemia
  10. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
  11. Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to initiation of therapy. The use of live vaccines within 30 days before initiation of therapy. IMiDs, PIs and or corticosteroids within 2 weeks prior to initiation of therapy. Other investigational therapies and monoclonal antibodies (mAb) within 4 weeks of initiation of therapy Prednisone up to but no more than 10 mg orally once daily (q.d.) or its equivalent for symptom management of comorbid conditions is permitted but dose should be stable for at least 7 days prior to initiation of therapy
  12. Residual side effects to previous therapy > Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 1 without pain are permitted)
  13. Prior peripheral stem cell transplant within 12 weeks of initiation of therapy
  14. Prior allogeneic stem cell transplantation with active graft-versus-host- disease
  15. Prior major surgical procedure or radiation therapy within 4 weeks of initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy)
  16. Known intolerance to the required dose and schedule of steroid therapy as determined by the investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03481556


Contacts
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Contact: VP Head of Clinical Development +4686152040 trials@oncopeptides.se

Locations
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United States, Florida
University of Florida Health Cancer Center Not yet recruiting
Gainesville, Florida, United States, 32610
Contact: Jan Moreb         
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Paul Richardson         
United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Yvonne Efebera         
Czechia
Fakultní nemocnice Brno Recruiting
Brno, Czechia
Contact: Ludek Pour         
Fakultní nemocnice Hradec Králové Recruiting
Hradec Králové, Czechia
Contact: Vladimir Maisnar         
Fakultní nemocnice Ostrava Recruiting
Ostrava, Czechia
Contact: Roman Hajek         
Všeobecná fakultní nemocnice Recruiting
Praha, Czechia
Contact: Jan Straub         
France
Hôpital Morvan Not yet recruiting
Brest, France
Contact: Jean-Richard Eveillard         
Centre Jean Bernard - Clinique Victor Hugo Not yet recruiting
Le Mans, France
Contact: Katell Le Du         
Hôpital privé du Confluent Not yet recruiting
Nantes, France
Contact: Jacques Delaunay         
Centre Hospitalier Lyon Sud Not yet recruiting
Pierre-Bénite, France
Contact: Lionel Karlin         
Centre Hospitalier Universitaire Institut Gustave Roussy Not yet recruiting
Villejuif, France
Contact: Vincent Ribrag         
Spain
Hospital Universitai Germans Trias i Pujol Recruiting
Badalona, Spain
Contact: Albert Oriol         
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain
Contact: Miquel Granell         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain
Contact: Joaquín Martinez         
Complejo Hospitalario de Salamanca Recruiting
Salamanca, Spain
Contact: María-Victoria Mateos         
Hospital Universitario Marques de Valdecilla Recruiting
Santander, Spain
Contact: Enrique Ocio         
Sponsors and Collaborators
Oncopeptides AB

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Responsible Party: Oncopeptides AB
ClinicalTrials.gov Identifier: NCT03481556     History of Changes
Other Study ID Numbers: OP-104
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Bortezomib
Daratumumab
Melphalan
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists