Informations générales (source: ClinicalTrials.gov)
A Multicentre Open-label Phase II Study of Ixazomib -Daratumumab Without Dexamethasone (IDara) in Elderly Relapse Refractory Multiple Myeloma (IDARA)
Interventional
Phase 2
University Hospital, Caen (Voir sur ClinicalTrials)
février 2019
décembre 2025
29 juin 2024
Multiple myeloma is an incurable hematological malignancy that affects older patients.
Currently, despite recent progress, the disease relapses more or less quickly after
initial treatment and requires the resumption of treatment with new drugs associated with
cortisone, whose side effects are important. The investigators propose to conduct a phase
2 testing the combination ixazomib - daratumumab without dexamethasone.
Etablissements
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CHU CAEN Dept of Hematology - 14033 - Caen - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Must be able to understand and voluntarily sign an informed consent form
- Must be able to adhere to the study visit schedule and other protocol requirements
- Age >= 65 years
- Subjects affiliated with an appropriate social security system.
- Life expectancy > 6 months
- Patients must have relapsed myeloma, and have been previously treated with
Bortezomib, Melphalan and Prednisone (VMP) or Lenalidomide and Dexamethasone (Rd),
or both:
- One or two line(s) of prior therapies
- Patients must have Progressive Disease as defined by the IMWG as one of the
following (Kumar, 2016): Increase of 25% from lowest response value in any one
or more of the following:
- Serum M-component (absolute increase must be ≥ 0.5 g/100 ml) and/or Urine
M-component (absolute increase must be ≥ 200 mg per 24 h) and/or
- Only in patients without measurable serum and urine M-protein levels: the
difference between involved and uninvolved FLC levels (absolute increase
must be > 10 mg/l).
- Bone marrow plasma cell percentage (absolute % must be ≥ 10%)
- Definite development of new bone lesions or soft tissue plasmacytomas or
definite increase in the size of existing bone lesions or soft tissue
plasmacytomas
- Development of hypercalcemia (corrected serum calcium > 11.5 mg/100 ml)
that can be attributed solely to the plasma cell proliferative disorder
- Patients must have undergone prior treatment with VMP or Rd:
- They must have received at least two cycles of therapy
- Either at diagnosis or relapse
- 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 > 200
mg/24H) In patients without measurable serum and urine M-protein levels when the
absolute serum Free Light chain (sFLC) is ≥100 mg/l and an abnormal sFLC K/λ ratio
(<0.26 and >1.65) is found (Dispenzieri, 2008).
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- 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
- Adequate organ function defined as: Serum creatinine clearance (MDRD formula) ≥30
ml/min ; Serum SGOT or SGPT < 3.0 X upper limit of normal (ULN) ; Serum total
bilirubin < 1.5 ULN
- Wash out period of at least 2 weeks from previous antitumor therapy or any
investigational treatment or 5 half-lives from previous antibodies.
- 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 Ixazomib and 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)
- 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: Intrauterine device (IUD) ; Hormonal (birth
control pills, injections, implants) ; Tubal ligation ; Partner's
vasectomy
- Additional effective methods: Male condom ; Diaphragm CervicalCap
- Serum (urine in the case where serum is not possible in a timely manner)
pregnancy test to be performed for all women of childbearing potential
regularly during the study, In addition, a pregnancy test may be done at any
time during the study at the discretion of the investigator if a subject misses
a period or has unusual menstrual bleeding.
- A woman of childbearing potential must remain on a highly effective method of
birth control. Contraception must begin 4 weeks before initiating treatment
with Ixazomib and Daratumumab, during therapy, during dose interruptions and
continuing for 4 months following discontinuation of Ixazomib and Daratumumab.
Reliable contraception is indicated even where there has been a history of
infertility, unless due to hysterectomy.
- A man who has not had a vasectomy and who is sexually active with a woman of
childbearing potential must agree to use a barrier method of birth control eg,
condom with spermicidal foam/gel/film/cream/suppository, and all men must also
not donate sperm during the study, for 4 months following discontinuation of
Ixazomib and Daratumumab. The exception to this restriction is that if the
subject's female partner is surgically sterile, a second method of birth
control is not required.
- Must be able to understand and voluntarily sign an informed consent form
- Must be able to adhere to the study visit schedule and other protocol requirements
- Age >= 65 years
- Subjects affiliated with an appropriate social security system.
- Life expectancy > 6 months
- Patients must have relapsed myeloma, and have been previously treated with
Bortezomib, Melphalan and Prednisone (VMP) or Lenalidomide and Dexamethasone (Rd),
or both:
- One or two line(s) of prior therapies
- Patients must have Progressive Disease as defined by the IMWG as one of the
following (Kumar, 2016): Increase of 25% from lowest response value in any one
or more of the following:
- Serum M-component (absolute increase must be ≥ 0.5 g/100 ml) and/or Urine
M-component (absolute increase must be ≥ 200 mg per 24 h) and/or
- Only in patients without measurable serum and urine M-protein levels: the
difference between involved and uninvolved FLC levels (absolute increase
must be > 10 mg/l).
- Bone marrow plasma cell percentage (absolute % must be ≥ 10%)
- Definite development of new bone lesions or soft tissue plasmacytomas or
definite increase in the size of existing bone lesions or soft tissue
plasmacytomas
- Development of hypercalcemia (corrected serum calcium > 11.5 mg/100 ml)
that can be attributed solely to the plasma cell proliferative disorder
- Patients must have undergone prior treatment with VMP or Rd:
- They must have received at least two cycles of therapy
- Either at diagnosis or relapse
- 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 > 200
mg/24H) In patients without measurable serum and urine M-protein levels when the
absolute serum Free Light chain (sFLC) is ≥100 mg/l and an abnormal sFLC K/λ ratio
(<0.26 and >1.65) is found (Dispenzieri, 2008).
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- 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
- Adequate organ function defined as: Serum creatinine clearance (MDRD formula) ≥30
ml/min ; Serum SGOT or SGPT < 3.0 X upper limit of normal (ULN) ; Serum total
bilirubin < 1.5 ULN
- Wash out period of at least 2 weeks from previous antitumor therapy or any
investigational treatment or 5 half-lives from previous antibodies.
- 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 Ixazomib and 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)
- 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: Intrauterine device (IUD) ; Hormonal (birth
control pills, injections, implants) ; Tubal ligation ; Partner's
vasectomy
- Additional effective methods: Male condom ; Diaphragm CervicalCap
- Serum (urine in the case where serum is not possible in a timely manner)
pregnancy test to be performed for all women of childbearing potential
regularly during the study, In addition, a pregnancy test may be done at any
time during the study at the discretion of the investigator if a subject misses
a period or has unusual menstrual bleeding.
- A woman of childbearing potential must remain on a highly effective method of
birth control. Contraception must begin 4 weeks before initiating treatment
with Ixazomib and Daratumumab, during therapy, during dose interruptions and
continuing for 4 months following discontinuation of Ixazomib and Daratumumab.
Reliable contraception is indicated even where there has been a history of
infertility, unless due to hysterectomy.
- A man who has not had a vasectomy and who is sexually active with a woman of
childbearing potential must agree to use a barrier method of birth control eg,
condom with spermicidal foam/gel/film/cream/suppository, and all men must also
not donate sperm during the study, for 4 months following discontinuation of
Ixazomib and Daratumumab. The exception to this restriction is that if the
subject's female partner is surgically sterile, a second method of birth
control is not required.
- Target disease exceptions: Solitary bone/solitary extramedullary plasmocytoma ;
Patients with non-secretory MM and non-measurable MM ; Evidence of central nervous
system (CNS) involvement
- Medical history and Concurrent disease:
- Subjects 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.
- Subject 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)
- Any 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
- Subjects with grade 2 or greater peripheral neuropathy (as per NCI-CTCAEv4.0)
- Subject 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.
- Known positive for HIV or active hepatitis B or C.
- Subjects 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
- Subjects 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.
- Subjects 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).
- Known GI disease or GI procedure that could interfere with the oral absorption
or tolerance of Ixazomib including difficulty swallowing.
- Physical and laboratory test findings:
- Patients on dialysis or with a Creatinine clearance < 30mL/min
- SGOT or SGPT >3ULN
- Prohibited prior therapies
- Prior local irradiation within two weeks before first dose
- Previous anti-CD38 therapy.
- Previous Ixazomib therapy
- Allergies and Adverse Drug Reaction:Known allergy to any of the study medications,
their analogues, or excipients in the various formulations of any agent.
- Refusal to consent or protected by a legal regime (guardianship, trusteeship)