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A PK Study of Melphalan During Treatment With Melflufen and Dex in RRMM Pat With Impaired Renal Function

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ClinicalTrials.gov Identifier: NCT03639610
Recruitment Status : Recruiting
First Posted : August 21, 2018
Last Update Posted : September 27, 2019
Sponsor:
Information provided by (Responsible Party):
Oncopeptides AB

Brief Summary:
This is a multicenter, PK study of Melphalan during treatment with Melflufen and Dexamethasone in patients with RRMM and impaired renal function. Received 1 - 4 prior lines of therapy and a renal function (creatinine clearance by Cockcroft-Gault formula) between ≥30 mL/min to <45 mL/min.

Condition or disease Intervention/treatment Phase
Renal Impairment RRMM Drug: Melflufen Drug: Dexamethasone Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study of the Pharmacokinetics of Melphalan During Treatment With Melflufen and Dexamethasone in Patients With Relapsed Refractory Multiple Myeloma and Impaired Renal Function
Actual Study Start Date : August 6, 2018
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020


Arm Intervention/treatment
Experimental: Single arm
Melflufen 40 mg iv Day 1 of each 28 day cycle Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle. If > 75 years of age 20 mg.
Drug: Melflufen
intravenous infusion

Drug: Dexamethasone
oral tablets




Primary Outcome Measures :
  1. Pharmakokinetics tmax [ Time Frame: Cycle 1 and 2 - three measurements post infusion. At Day 1 of each cycle (28 days cycles) ]

    Primary objective is to evaluate the relationship between renal function and the PK. Several PK parameters will be assessed.

    • Time of maximum observed concentration (tmax)


  2. Pharmakokinetics Cmax [ Time Frame: Cycle 1 and 2 - three measurements post infusion. At Day 1 of each cycle (28 days cycles) ]
    • Maximum observed concentration (Cmax)

  3. Pharmakokinetics AUC0-t [ Time Frame: Cycle 1 and 2 - three measurements post infusion. At Day 1 of each cycle (28 days cycles) ]
    • Area under the concentration versus time curve between 0h and end of drug infusion (AUC0-t)

  4. Pharmakokinetics AUCinf [ Time Frame: Cycle 1 and 2 - three measurements post infusion. At Day 1 of each cycle (28 days cycles) ]
    • Area under the concentration versus time curve from 0h to infinity (AUCinf)

  5. Pharmakokinetics t1/2 [ Time Frame: Cycle 1 and 2 - three measurements post infusion. At Day 1 of each cycle (28 days cycles) ]
    • Elimination phase half-life (t½)

  6. Pharmakokinetics CL [ Time Frame: Cycle 1 and 2 - three measurements post infusion. At Day 1 of each cycle (28 days cycles) ]
    • Clearance (CL) parameters for melphalan during treatment with melflufen

  7. Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) [ Time Frame: From screening to 30 days after last dose ]
    Primary objective is to assess the safety and tolerability of melflufen in patients with moderate renal impairment


Secondary Outcome Measures :
  1. ORR [ Time Frame: From initiation of therapy until disease progression. For an average patient this is achieved within 6 months. ]
    To assess the best tumor response as well as overall response rate

  2. PFS [ Time Frame: From initiation of therapy until disease progression or initiation of new therapy. For an average patient thius is reached after 6 month. ]
    To assess progression free survival

  3. DOR [ Time Frame: From confirmed response until disease progression. For an average patient this last for approximatel 8-9 months. ]
    To assess duration of response (DOR) in patients with ≥ PR (stringent complete response (sCR), complete response (CR), very good partial response (VGPR), PR) as best response

  4. CBR [ Time Frame: During treatment, for an average patient this is approximately 6 months ]
    To assess clinical benefit rate (CBR) and duration of clinical benefit (i.e., proportion of patients with ≥ MR) as best response

  5. TTR [ Time Frame: From initiation of therapy until documented disease response. For an average patient this is achieved within 6 months. ]
    To assess time to response (TTR) in patients with a PR or better



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 MM with documented disease progression
  3. 2 - 4 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 MM 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. Renal function: Estimated eGFR by CKD-EPI formula between ≥30 mL/min to <45 mL/min at screening and at Cycle 1 Day 1 for cohort 1, between ≥15 mL/min to < 30 mL/min for cohort 2.
  11. The following laboratory results must be met during screening 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 study therapy)
    • Platelet count ≥ 75,000 cells/mm3 (75 x 109/L) (without transfusions during the 10 days prior to initiation of study therapy)
    • Hemoglobin ≥ 8.0 g/dL (red blood cell [RBC] transfusions are permitted)
    • Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), or higher in patients diagnosed with Gilberts syndrome that have been reviewed and approved by the medical monitor.
    • AST/SGOT and ALT/SGPT ≤ 3.0 x ULN.
  12. 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 platelet transfusion refractory (platelet count fails to increase by > 10,000 cells/mm3 [10.0 x 109/L] after a 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 MM 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 corticosteroids within 14 days prior to initiation of study therapy. Other investigational therapies and monoclonal antibodies within 4 weeks of initiation of study therapy. Prednisone up to but no more than 10 mg orally 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 study therapy. Plasmapheresis is not permitted within 14 days of initiation of therapy.
  12. Residual side effects to previous therapy > Grade 1 prior to enrollment (Alopecia any grade and/or neuropathy Grade 2 without pain are permitted)
  13. Prior peripheral stem cell transplant within 12 weeks of initiation of study 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 the initiation of study therapy (this does not include limited course of radiation used for management of bone pain to be completed within 7 days of initiation of study therapy).
  16. Known intolerance to steroid therapy
  17. Prior renal transplant
  18. Currently in need of renal dialysis

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): NCT03639610


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

Locations
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Czechia
University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology Recruiting
Brno, Czechia
Contact: Ludek Pour         
University Hospital Hradec Kralove, 4th Internal Clinic of Hematology Recruiting
Kralovice, Czechia
Contact: Vladimir Maisnar         
University Hospital Olomouc, Clinic of Hemato-Oncology Recruiting
Olomouc, Czechia
Contact: Jiri Minarik         
General University Hospital in Prague, 1st Internal Clinic - Clinic of Hematology Recruiting
Praha, Czechia
Contact: Ivan Spicka         
Greece
General Hospital of Athens "Evangelismos" Recruiting
Athens, Greece
Contact: Sosana Delimpasi         
General Hospital of Athens Alexandra, Therapeutic Clinic Not yet recruiting
Athens, Greece
Contact: Meletios-Athanasios Dimopoulos         
University General Hospital of Patras Recruiting
Patra, Greece
Contact: Anargyros Symeonidis         
General Hospital of Thessaloniki "G. Papanikolaou" Recruiting
Thessaloníki, Greece
Contact: Ioanna Sakellari         
Theageneio Anticancer Hospital of Thessaloniki Not yet recruiting
Thessaloníki, Greece
Contact: Eirini Katodritou         
Poland
Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka Recruiting
Toruń, Torun, Poland
Contact: Marcin Rymko         
Maria Sklodowska-Curie Institute of Oncology, Branch in Gliwice, Department of Bone Marrow Transplantation and Hematologic Oncology Recruiting
Gliwice, Poland
Contact: Jacek Najda         
Independent Public Healthcare Facility Municipal Hospitals, Department of Hematology Recruiting
Katowice, Poland
Contact: Sebastian Grosicki         
Independent Public Teaching Hospital No.1 in Lublin, Department of Hematooncology, Bone Marrow Transplantation and Chemotherapy Recruiting
Lublin, Poland
Contact: Wojciech Legiec         
Oncology Center of Warmia and Mazury in Olsztyn, Teaching Department of Hematology Recruiting
Olsztyn, Poland
Contact: Janusz Halka         
Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz, Department of Haematology and Subdepartment of Chemotherapy - Teaching Department of Haematology Recruiting
Łódź, Poland
Contact: Tadeusz Robak         
Sponsors and Collaborators
Oncopeptides AB

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Responsible Party: Oncopeptides AB
ClinicalTrials.gov Identifier: NCT03639610     History of Changes
Other Study ID Numbers: OP-107
First Posted: August 21, 2018    Key Record Dates
Last Update Posted: September 27, 2019
Last Verified: September 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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Renal Insufficiency
Kidney Diseases
Urologic Diseases
Dexamethasone
Dexamethasone acetate
Melphalan
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors