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Trial record 1 of 1 for:    NCT04412707
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A PK, Safety and Tolerability Study of Peripheral and Central Infusion of Melflufen in RRMM Patients (PORT)

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ClinicalTrials.gov Identifier: NCT04412707
Recruitment Status : Recruiting
First Posted : June 2, 2020
Last Update Posted : October 23, 2020
Sponsor:
Information provided by (Responsible Party):
Oncopeptides AB

Brief Summary:
This is a randomized, two-period, cross-over Phase 2 study, comparing PK, and assessing safety and tolerability and efficacy of peripheral and central intravenous administration of melflufen in patients with RRMM. It is an international study, enrolling patients in US and Europe. The study will enroll patients following at least 2 lines of prior therapy.

Condition or disease Intervention/treatment Phase
RRMM Drug: Melphalan-Flufenamide Drug: Dexamethasone Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Two-period, Cross-over, Ph 2 Study, Comparing Pharmacokinetics, and Assessing Safety and Tolerability of Peripheral and Central i.v. Administration of Melphalan Flufenamide (Melflufen) in RRMM Patients
Actual Study Start Date : August 4, 2020
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2022


Arm Intervention/treatment
Active Comparator: Arm A
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. Cycle 1 will be administered via a PVC and cycle 2 and onwards melflufen will be administered via a CVC.
Drug: Melphalan-Flufenamide
Peripheral versus central administration
Other Name: melflufen

Drug: Dexamethasone
Oral tablets

Active Comparator: Arm B
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. Cycle 1 will be administered via a CVC and cycle 2 will be administered via a PVC. From cycle 3 and onwards melflufen will be administered via CVC.
Drug: Melphalan-Flufenamide
Peripheral versus central administration
Other Name: melflufen

Drug: Dexamethasone
Oral tablets




Primary Outcome Measures :
  1. Peak Plasma Concentration for melflufen and melphalan [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle) ]
    To evaluate and compare the pharmacokinetic (PK) variable Cmax of melflufen and melphalan after central and peripheral intravenous infusion of melflufen.

  2. Area under the plasma concentration versus time curve AUC(0-t) of melflufen and melphalan [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle) ]
    To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melflufen and melphalan after central and peripheral intravenous infusion of melflufen.

  3. Area under the plasma concentration versus time curve AUC(0-inf) of melflufen and melphalan [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle) ]
    To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melflufen and melphalan after central and peripheral intravenous infusion of melflufen

  4. Frequency and Grade of local reactions including phlebitis at infusion site after peripheral intravenous administration [ Time Frame: 15 minutes and 4 hours after peripheral intravenous administration ]
    To assess the local tolerability of peripheral intravenous administration of melflufen


Secondary Outcome Measures :
  1. Peak Plasma Concentration for desethyl-melflufen [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle) ]
    To evaluate and compare the pharmacokinetic (PK) variable Cmax of desethyl-melflufen after central and peripheral intravenous infusion of melflufen.

  2. Area under the plasma concentration versus time curve AUC(0-t) of desethyl-melflufen [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle) ]
    To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of desethyl-melflufen after central and peripheral intravenous infusion of melflufen

  3. Area under the plasma concentration versus time curve AUC(0-inf) of desethyl-melflufen [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle) ]
    To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of desethyl-melflufen after central and peripheral intravenous infusion of melflufen

  4. Elimination half-life (t1/2) of melflufen, melphalan and desethyl-melflufen [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle) ]
    To evaluate elimination half-life (t½) for melflufen, melphalan and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.

  5. Frequency and Grade of Treatment emergent Adverse Events (TEAEs) [ Time Frame: From screening to 30 days after last dose ]
    To assess safety and general tolerability of melflufen

  6. Best Response (stringent complete response (sCR)) [ Time Frame: From initiation of therapy until disease progression. For an average patient this is achieved within 6 months. ]
    To assess best response during the study

  7. 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

  8. CBR [ Time Frame: During treatment, for an average patient this is approximately 6 months. ]
    To assess clinical benefit rate (CBR) i.e., proportion of patients that achieve a confirmed minimal response or better (sCR, CR, VGPR, PR and MR).

  9. DOR [ Time Frame: From confirmed response until disease progression. For an average patient this last for approximately 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.

  10. DOCB [ Time Frame: From first evidence of confirmed assessment of sCR, CR, VGPR, PR or MR to first confirmed disease progression, or to death due to any cause, assessed up to 2 years. . ]
    To assess duration of clinical benefit (DOCB) in patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), PR, or MR.

  11. 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 PR or better.

  12. TTP [ Time Frame: From date of randomization until documented disease progression. For an average patient this is achieved within 6 months. ]
    To assess time to progression(TTP).

  13. TTNT [ Time Frame: From randomization to the date of next anti-myeloma treatment. For an average patient this is achieved within 9 months. ]
    To assess time to next treatment (TTNT)

  14. PFS [ Time Frame: From initiation of therapy until documented disease progression or initiation of new therapy. For average this is reached after 6 months, ]
    To assess progression free survival



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. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol;
  3. A prior diagnosis of MM with documented disease progression in need of treatment at time of screening;
  4. Measurable disease defined as any of the following:

    • Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP)
    • ≥ 200 mg/24hr of monoclonal protein in the 24hour urine collection by electrophoresis (UPEP)
    • Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain (FLC) ratio
  5. Received at least 2 prior lines of therapy and is refractory to an IMiD and a PI. The definition of refractory includes intolerance to an IMiD/PI after at least two 28-day cycles of therapy, see Appendix 10 and Appendix 8.
  6. Adequate peripheral arm veins for repeated intravenous infusions
  7. Life expectancy of ≥ 6 months;
  8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, see Appendix 6. Patients with ECOG performance status > 2 solely based on bone pain secondary to MM may be eligible following consultation and approval of medical monitor;
  9. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec, see Appendix 11
  10. Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before study treatment 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 treatment)
    • Platelet count ≥ 75,000 cells/ mm3 (75 x 109/L) (without 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), except 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 glomerular filtration rate (eGFR) by CKD-EPI formula of ≥ 45 mL/min, see Appendix 12.
  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 [CVC]) and a PVC;
  12. a) Male patients: A male patient is eligible if he agrees to use contraception as detailed in Appendix 4 of this protocol during the treatment period and for at least 3 months after the last dose of study treatment and refrains from donating sperm during this period b) Female patients: A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: I. Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 or II. A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the treatment period and for at least 28 days after the last dose of study treatment

Exclusion Criteria:

  1. Primary refractory disease (i.e. never responded with at least MR to any prior therapy);
  2. Evidence of mucosal and/or internal bleeding or platelet transfusion refractory (platelet count fails to increase by > 10,000 cells/mm3 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 cardiac conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months);
  4. Known active infection that is uncontrolled or has required intravenous systemic therapy within 14 days of randomization. Patients that have required oral anti-infective treatment within 14 days of randomization should be discussed with the Medical Monitor;
  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. Human immunodeficiency virus (HIV) or active hepatitis B or C viral infection;
  9. Concurrent known or suspected amyloidosis or plasma cell leukemia;
  10. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes);
  11. Known central nervous system (CNS) or meningeal involvement of myeloma
  12. Any of the following treatments, within the specified timeframe

    • 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 or corticosteroids within 2 weeks prior to initiation of therapy.
    • Other investigational therapies and monoclonal antibodies within 4 weeks of initiation of 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 therapy.

    Other washout times may be considered following consultation with the medical monitor.

  13. 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);
  14. Prior stem cell transplant (autologous and/or allogenic) within 6 months of initiation of therapy;
  15. Prior allogeneic stem cell transplantation with active graft-versus-host-disease;
  16. Prior major surgical procedure or radiation therapy within 4 weeks of the initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy);
  17. Known intolerance to the required dose and schedule of steroid therapy, as determined by the investigator;
  18. Known hypersensitivity reaction to melphalan, melflufen or its excipients
  19. Prior treatment with melflufen

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): NCT04412707


Contacts
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Contact: VP Chief Operating Officer +4686152040 trials@oncopeptides.com

Locations
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United States, California
The Oncology Institute of Hope & Innovation - Glendale Recruiting
Glendale, California, United States, 91204
Contact: Amitabha Mazumder         
Bulgaria
University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Clinical Hematology Clinic Recruiting
Plovdiv, Bulgaria
Contact: Vasko Graklanov         
Multiprofile Hospital for Active Treatment - Sofia, part of Military Medical Academy, Clinic of Hematology and Oncology Recruiting
Sofia, Bulgaria
Contact: Julian Raynov         
Specialized Hospital for Active Treatment of Hematological Diseases, Sofia Recruiting
Sofia, Bulgaria
Contact: Kameliya Simeonova         
Multiprofile Hospital for Active Treatment "Sveta Marina", Varna Not yet recruiting
Varna, Bulgaria
Contact: Ilina Micheva         
Czechia
University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology Recruiting
Brno, Czechia, 62500
Contact: Ludek Pour         
University Hospital Olomouc, Clinic of Hemato-Oncology Recruiting
Olomouc, Czechia, 77900
Contact: Jiri Minarik         
Hungary
Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases, Department of Hematology and Stem Cell Transplantation Not yet recruiting
Budapest, Hungary
Contact: Gabor Mikala         
Semmelweis University, 3rd Department of Internal Medicine Recruiting
Budapest, Hungary
Contact: Tamas Masszi         
Ukraine
Public Non-Profit Enterprise "City Clinical Hospital #4" under Dnipro City Council, Regional Hematology Center Recruiting
Dnipro,, Ukraine
Contact: Hanna Usenko         
Public Non-Profit Enterprise "Kyiv City Clinical Hospital #9" under the Executive Body of Kyiv City Council, Hematology Department #1 Recruiting
Kyiv, Ukraine
Contact: Ulyana Melnyk         
Institute of Blood Pathology and Transfusion Medicine, Department of Hematology with Laboratory Group Recruiting
Lviv, Ukraine
Contact: Zvenyslava Masliak         
Communal Nonprofit Enterprise "Vinnytsia Regional Clinical Hospital named after N.I. Pirogov Vinnytsia Regional Council", Clinical Highly Specialized Hematology Department Recruiting
Vinnytsia, Ukraine
Contact: Hanna Oliynyk         
Sponsors and Collaborators
Oncopeptides AB
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Responsible Party: Oncopeptides AB
ClinicalTrials.gov Identifier: NCT04412707    
Other Study ID Numbers: OP-109
First Posted: June 2, 2020    Key Record Dates
Last Update Posted: October 23, 2020
Last Verified: October 2020
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
Keywords provided by Oncopeptides AB:
central intravenous administration
peripheral intravenous administration
Additional relevant MeSH terms:
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Dexamethasone
Melphalan
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
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors