A Study of VLX1570 and Dexamethasone in Myeloma Patients

Phase 1

Conditions: Multiple Myeloma
MedDRA version: 19.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864
MedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-004282-31-FI

Lead Sponsor: Vivolux AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 62

Inclusion Criteria

1. Diagnosis of relapsed or relapsed and refractory multiple myeloma, or intolerant to established therapy following at least 2 prior therapies. Prior therapies must include at least one immunomodulatory drug (e.g., thalidomide, lenalidomide or pomalidomide) and one proteasome inhibitor (e.g., bortezomib or carfilzomib); i.e., regimens known to provide clinical benefits.
2. Measurable disease defined by 1 or more of the following:
a. Serum monoclonal protein = 0.5 g/dL
b. Urine monoclonal protein >200 mg/24 hour
c. Serum immunoglobulin free light chain >10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65)
3. Estimated glomerular filtration rate (GFR) =30 mL/min as assessed by CKD-epi, MDRD, or the Cockcroft-Gault Equation (Appendix 4).
4. Age =18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
6. Females of child-bearing potential* must have a negative pregnancy test.
* A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
7. Males and females of childbearing potential must be willing to use an effective form of contraception (see below) during chemotherapy treatment and for at least six months thereafter.
Such methods include: (if using hormonal contraception this method must be supplemented with a barrier method, preferably male condom).
o combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
o oral
o intravaginal
o transdermal
o progestogen-only hormonal contraception associated with inhibition of ovulation:
o oral
o injectable
o implantable
o intrauterine device (IUD)
o intrauterine hormone-releasing system ( IUS)
o bilateral tubal occlusion
o vasectomised partner
o true sexual abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.
8. Absolute neutrophil count (ANC) =1.0 x 109 /L, hemoglobin =8 g/dL (transfusion permitted provided the anemia is judged to be disease related), and platelet count = 75 x 109/L.
9. Adequate hepatic function, with bilirubin < 1.5 x the ULN, and AST and ALT < 2.5 x ULN.
10. Patient has or is willing to have a central venous catheter (e.g., PICC, Port-A-Cath®, Hickman® catheter) for drug administration.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 31
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion Criteria

1. Any concurrent treatment that would compromise the study including but not limited to:
a. Planned concurrent treatment for multiple myeloma other than bisphosphonates
b. Ongoing corticosteroids for indications other than multiple myeloma allowed as long as the dose does not exceed 10 mg of prednisone per day or equivalent
c. Persisting effects of any previous or ongoing treatment = grade 1 that might compromise delivery of study treatment or assessment of adverse events (except alopecia or neuropathy = grade 2 without pain)
2. Any cytotoxic or biologic therapy less than 2 weeks prior to initiation of therapy.
3. Pregnant or breast feeding females.
4. Hypertension or diabetes not adequately controlled with current medication, defined as a need for dose adjustment or implementation of new or additional drugs as judged by the Investigator.
5. Known active hepatitis B or C infection or HIV infection.
6. Significant cardiovascular disease with NYHA Class III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia.
7. QTc interval >460 msec (males) or >470 msec (females); or repeated demonstration of a QTc interval >450 msec.
8. A history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT syndrome).
9. The use of concomitant medications that prolong the QT/QTc interval.
10. Uncontrolled intercurrent illness including but not limited to psychiatric illness/social situations that, in the opinion of the Investigator, would compromise compliance of study requirements or put the patient at unacceptable risk.
11. Active infection requiring systemic treatment within one week prior to first dose.
12. Major surgery within 1 month prior to enrollment.
13. Use of any investigational agent within the last 28 days. For classes of investigational agents that are not known to have prolonged toxicities the wash-out time may be decreased to 14 days after agreement with the Medical Monitor.
14. History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) except if the patient has been free of symptoms and without active therapy for at least 2 years.
15. Known intolerance to steroids or H1/H2-antagonists.
16. Serum calcium (corrected for albumin) level above the ULN range (treatment of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal with standard treatment).
17. Diagnosed with plasma cell leukemia, POEMS syndrome or amyloidosis.
18. Patients with a history of central nervous system (CNS) myeloma or other CNS malignancy.