Daratumumab in treatment of resistant or refractory Multiple myeloma

Phase 1

• Conditions: Multiple Myeloma resistant or refractory to Bortezomib and Lenalidomide and Pomalidomide; Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 18.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864

• Registration Number: EUCTR2015-002221-19-FR
• Lead Sponsor: CHRU of Lille

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-08-06
• Last Update Posted: 2 June 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1.Must be able to understand and voluntarily sign an informed consent form
2.Must be able to adhere to the study visit schedule and other protocol requirements
3.Age ³ 18 years
4.Life expectancy > 6 months
5.Patients must have relapsed myeloma, and previously treated with Bortezomib, Lenalidomide, and Pomalidomide treatment, and being resistant or refractory to Bortezomib and Lenalidomide and Pomalidomide treatment. 6.Patients must have a clearly detectable and quantifiable monoclonal M-component value:
?IgG (serum M-component > 10g/l)
?IgA (serum M-component >5g/l)
?IgD (serum M-component > 0.5g/l)
?Light chain (serum M-component >1g/l or Bence Jones > 200mg/24H)
?In patients without measurable serum and urine M-protein levels when the absolute serum FreeLight chain (sFLC) is =100 mg/l and an abnormal sFLC K/? ratio (<0.26 and >1.65) is found (Dispenzieri, 2008).
7.Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
8.Adequate bone marrow function within 5 days prior to 1st drug intake (cycle1, day 1, C1D1), without transfusion nor growth factor support within 5 days prior to 1st drug intake , defined as:
?Absolute neutrophils = 1000/mm3
?Platelets = 50000/mm3
?Haemoglobin = 8.5g/dl
9.Adequate organ function defined as:
?Serum creatinine clearance (Cockcroft-Gault formula) =30 ml/min
?Serum SGOT or SGPT < 3.0 X upper limit of normal (ULN)
?Serum total bilirubin < 2.0 mg/dL
10.Wash out period of at least 2 weeks from previous antitumor therapy or any investigational treatment or 5 half-lives from previous antibodies.
11.Women who are partners of men and of childbearing potential must be practicing one of the following methods of birth control: subcutaneous hormonal implant, levonorgestrel releasing intra-uterine system, medroxyprogesterone acetate depot, tubal sterilization, ovulation inhibitory progesterone only pills, or sexual intercourse with a vasectomized male partner (vasectomy must be confirmed by 2 negative semen analyses). Or women will commit to absolute and continuous abstinence confirmed to her physician on a monthly basis. Childbearing potential*. Contraception will start during therapy including dose interruptions, for 4 months after discontinuation of Daratumumab.
*: Criteria for women of childbearing potential :
This protocol defines a female of childbearing potential as a sexually mature woman who:
1) has not undergone a hysterectomy or bilateral oophorectomy or
2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months)

12.A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 28 days prior to dosing and the second within 48 hours prior to dosing, and remain on a highly effective method of birth control. The two methods of reliable contraception must include one highly effective method and one additional effective (barrier) method. FCBP must be referred to a qualified provider of contraceptive methods if needed. The following are examples of highly effective and additional effective methods of contraception:
•Highly effective methods:
oIntrauterine device (IUD)
oHormonal (birth control pills, injections, implants)
oTubal ligation
oPartner’s vasectomy
•Additional effective methods:
o

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not eligible to enrol in this study:
1.Target disease exceptions:
oSolitary bone/solitary extramedullary plasmocytoma
oPatients with non-secretory MM and non-measurable MM
oEvidence of central nervous system (CNS) involvement

2.Medical history and Concurrent disease:
oSubjects with prior (= 5 years) or concurrent invasive malignancies except the following:
?Adequately treated basal cell or squamous cell skin cancer
?Incidental finding of low grade (Gleason 3+3 or less) prostate cancer
?Any cancer from which the subject has been disease free for at least 3 years.
oSubject with known/underlying medical conditions that, in the investigator’s opinion would make the administration of the study drug hazardous (ie: uncontrolled diabetes or uncontrolled coronary artery disease)
oAny uncontrolled or severe cardiovascular or pulmonary disease determined by the investigator including:
?NYHA functional classification III or IV congestive heart failure
?LVEF ( Left Ventricular Ejection Fraction) =45%
?Uncontrolled angina, hypertension or arrhythmia
?Myocardial infarction in the past 6 months
oSubjects with grade 2 or greater peripheral neuropathy (as per NCI-CTCAEv4.0)
oSubject is a woman who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 4 months after the last dose of any component of the treatment regimen. Or, subject is a man who plans to father a child while enrolled in this study or within 4 months after the last dose of any component of the treatment regimen.
oKnown positive for HIV or active hepatitis B or C.
oSubjects with psychiatric illnesses or social situations that would preclude them understanding the informed consent, study compliance or the ability to tolerate study procedures and/or study therapy
oSubjects with known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) < 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal.
oSubjects with a history of moderate or severe persistent asthma within the past 2 years (see appendix), or with uncontrolled asthma of any classification at the time of screening (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
3.Physical and laboratory test findings:
oPatients on dialysis or with a Creatinine clearance < 30mL/min
oSGOT or SGPT >3ULN
4.Prohibited prior therapies
oPrior local irradiation within two weeks before first dose
oPrevious anti-CD38 therapy.
5.Allergies and Adverse Drug Reaction:
oHypersensitivity to Dexamethasone that would prohibit treatment with study therapy
6.Refusal to consent or protected by a legal regime (guardianship, trusteeship)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified