Clinical trial NCT02244125 (phase 2, status: unknown status)
Conditions: multiple myeloma, first relapse
ICD codes: C90.01, C90.02, C90.00
Drugs: pcd
SMILES: NC1=CC=CC2=C1C(=O)N(C1CCC(=O)NC1=O)C2=O
Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have been treated in first line within the IFM/DFCI 2009 trial to be
             treated within the PCD trial in second line

          2. Must be able to understand and voluntarily sign an informed consent form

          3. Must be able to adhere to the study visit schedule and other protocol requirements

          4. Age: 18-70 years

          5. Life expectancy >6 months

          6. Patients must have progressive (+/- symptomatic) Myeloma as defined by the IMWG
             criteria with increase of ≥25% from lowest response value in any one or more of the
             following:

               -  Serum M-component and/or (the absolute increase must be ≥0.5 g/dl)

               -  Urine M-component and/or (the absolute increase must be ≥200 mg/24h)

               -  Only in patients without measurable serum and urine M-protein levels: the
                  difference between involved and uninvolved FLC levels. The absolute increase must
                  be >10 mg/dl

               -  Bone marrow plasma cell percentage; the absolute percentage 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 hypercalcaemia (corrected serum calcium >11.5 mg/dl or 2.65mmol/l)
                  that can be attributed solely to the plasma cell proliferative disorder.

          7. 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 and in the
                  absence of renal failure: when the absolute serum FreeLightChain (sFLC) is
                  ≥100mg/l and an abnormal sFLC K/λ ratio (<0.26 or>1.65) is found.

          8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

          9. Adequate bone marrow function, documented within 96 hours prior to treatment without
             transfusion or growth factor support, defined as:

               -  Absolute neutrophils ≥1000/mm3

               -  Platelets ≥75000/mm3

               -  Hemoglobin ≥8.5g/dl

         10. Adequate organ function, documented within 96 hours prior to treatment, defined as:

               -  Serum SGOT/AST or SGPT/ALT <3.0 X Upper Limit of Normal (ULN)

               -  Serum creatinine clearance (Cockcroft-Gault formula) ≥50 ml/min

               -  Serum total bilirubin <2.0 mg/dl

         11. Wash out period of at least 2 weeks from previous antitumor therapy or any
             investigational treatment.

         12. Able to take antithrombotic medicines such as low molecular weight heparin or aspirin.

         13. Subjects affiliated with an appropriate social security system

         14. Agree to abstain from donating blood while taking study drug therapy and for at least
             28 days following discontinuation of study drug therapy

         15. Agree not to share study medication with another person and to return all unused study
             drug to the investigator

         16. Female subjects of childbearing potential (*) must:

               -  Understand the potential teratogenic risk to the unborn child

               -  Understand the need and agree to use, and be able to comply with, two reliable
                  forms of contraception simultaneously or to practice complete abstinence from
                  heterosexual contact during the following time periods related to this study:

                    1. for at least 28 days before starting study drug;

                    2. while participating in the study;

                    3. dose interruptions; and

                    4. for at least 28 days after study treatment discontinuation.

             The two methods of reliable contraception must include one highly effective method and
             one additional effective (barrier) method. Females of childbearing potential 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

                    -  Cervical Cap

             Because of the increased risk of venous thromboembolism in patients with multiple
             myeloma taking pomalidomide and cyclophosphamide and dexamethasone, combined oral
             contraceptive pills are not recommended. If a female subject is currently using
             combined oral contraception the patient should switch to another one of the highly
             effective methods listed above. The risk of venous thromboembolism continues for 4-6
             weeks after discontinuing combined oral contraception. The efficacy of contraceptive
             steroids may be reduced during co-treatment with dexamethasone.

             Implants and levonorgestrel-releasing intrauterine devices are associated with an
             increased risk of infection at the time of insertion and irregular vaginal bleeding.
             Prophylactic antibiotics should be considered particularly in patients with
             neutropenia.

             o Agree to have pregnancy testing based on the frequency outlined below.

             Medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/ml must be
             performed for females of childbearing potential, including females of childbearing
             potential who commit to complete abstinence:

               -  Before starting study drug: females of childbearing potential must have two
                  negative pregnancy tests prior to starting study drug. The first pregnancy test
                  must be performed within 10-14 days prior to the start of study drug and the
                  second pregnancy test must be performed within 24 hours prior to the start of
                  study drug. The patient may not receive study drug until the study doctor has
                  verified that the results of these pregnancy tests are negative.

               -  During study participation and for 28 days following study drug discontinuation:

             Females of childbearing potential with regular or no menstrual cycles must agree to
             have pregnancy tests weekly for the first 28 days of study participation and then
             every 28 days while on study, at study discontinuation, and at day 28 following study
             drug discontinuation.

             If menstrual cycles are irregular, the pregnancy testing must occur weekly for the
             first 28 days and then every 14 days while on study, at study discontinuation, and at
             days 14 and 28 following study drug discontinuation.

             *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).

         17. Male subjects must:

               -  Practice complete abstinence or agree to use a condom during sexual contact with
                  a pregnant female or a female of childbearing potential while participating in
                  the study, during dose interruptions and for at least 28 days following study
                  drug discontinuation, even if he has undergone a successful vasectomy.

               -  Agree not to donate semen or sperm during study drug therapy and for at least 28
                  days following discontinuation of study drug.

        Exclusion Criteria:

          1. Any other uncontrolled medical condition or comorbidity that might interfere with
             subject's participation

          2. Primary amyloidosis or myeloma complicated by amyloidosis

          3. Pregnant or breast feeding females

          4. Use of any other experimental drug or therapy within 2 weeks before study treatment
             initiation (except local radiotherapy and/or corticosteroid until dose of
             dexamethasone 160mg)

          5. Known positive for HIV or Active infectious hepatitis, type B or C

          6. Patients with non-secretory MM

          7. Prior history of malignancies within 10 years

          8. Evidence of Central Nervous System (CNS) involvement

          9. Any >grade 2 toxicity unresolved

         10. Peripheral neuropathy >grade 2

         11. Known hypersensitivity to thalidomide, lenalidomide, cyclophosphamide or dexamethasone

         12. Ongoing active infection, especially ongoing pneumonitis

         13. Participant with clinical signs of heart or coronary failure, or evidence of Left
             Ventricular Ejection Fraction (LVEF) inferior to 40%.

             Participant with myocardial infarction within 6 months prior to enrolment or have New
             York Heart Association (NYHA) Class III or IV heart failure, and controlled angina,
             severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities

         14. Inability or unwillingness to comply with birth control requirements

         15. Unable to take antithrombotic medicines at study entry

         16. Unable to take corticotherapy at study entry

         17. Scheduled vaccination with a live agent such as yellow fever vaccine

         18. Individually deprived of liberty or placed under the authority of a tutor