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A PK Study of Melphalan During Treatment With Melphalan Flufenamide (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 : May 4, 2021
Sponsor:
Information provided by (Responsible Party):
Oncopeptides AB

Tracking Information
First Submitted Date  ICMJE August 14, 2018
First Posted Date  ICMJE August 21, 2018
Last Update Posted Date May 4, 2021
Actual Study Start Date  ICMJE August 6, 2018
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A PK Study of Melphalan During Treatment With Melphalan Flufenamide (Melflufen) and Dex in RRMM Pat With Impaired Renal Function
Official Title  ICMJE A Study of the Pharmacokinetics of Melphalan During Treatment With Melflufen and Dexamethasone in Patients With Relapsed Refractory Multiple Myeloma and Impaired Renal Function
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 2 - 4 prior lines of therapy and a renal function (creatinine clearance by Cockcroft-Gault formula) between ≥30 mL/min to <45 mL/min in Cohort 1,and ≥15 mL/min to <30 mL/min in Cohort 2.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Renal Impairment
  • RRMM
Intervention  ICMJE
  • Drug: Melphalan flufenamide (melflufen)
    intravenous infusion
  • Drug: Dexamethasone
    oral tablets
Study Arms  ICMJE Experimental: Single arm

Cohort 1A Melphalan flufenamide 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.

Cohort 1B Melphalan flufenamide 30 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.

Cohort 2A Melphalan flufenamide 20 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.

Cohort 2B Melphalan flufenamide 30 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.

Interventions:
  • Drug: Melphalan flufenamide (melflufen)
  • Drug: Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 19, 2021)
35
Original Estimated Enrollment  ICMJE
 (submitted: August 20, 2018)
25
Estimated Study Completion Date  ICMJE September 30, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 1A and 1B, between ≥15 mL/min to < 30 mL/min for cohort 2A and 2B.
  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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: VP Head of Clinical development +4686152040 trials@oncopeptides.se
Listed Location Countries  ICMJE Czechia,   Greece,   Poland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03639610
Other Study ID Numbers  ICMJE OP-107
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Oncopeptides AB
Study Sponsor  ICMJE Oncopeptides AB
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Oncopeptides AB
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP