Overview

Cyclophosphamide With Biochemical Progression During Lenalidomide-Dexamethasone Treatment for Relapsed/Refractory Multiple Myeloma (MM)

Status:
Completed
Trial end date:
2018-07-01
Target enrollment:
0
Participant gender:
All
Summary
This study evaluates the efficacy of the addiction of Cyclophosphamide to Revlimid-low dose dexamethasone (Rd) in relapsed/refractory Multiple Myeloma patients, who experienced a biochemical progression, without CRAB, during Rd treatment.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Fondazione EMN Italy Onlus
Fondazione Neoplasie Sangue Onlus
Treatments:
BB 1101
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Thalidomide
Criteria
Inclusion Criteria:

- Patient with relapse/refractory multiple myeloma who experienced biochemical
progression, without CRAB, during treatment with Rd. CRAB means the presence of organ
damage, multiple myeloma related (renal impairment and/or anemia and/or new bone
lesions and/or hypercalcemia). It is sufficient one of the previous signs for defining
the presence of CRAB. Biochemical progression means: positivization of serum/urine
immunofixation for patients who reached a complete remission with Rd treatment or at
least 25% increment of monoclonal component in serum/urine for patients who reached at
least a stable disease (SD).

- Patient exposed to previous therapy included Lenalidomide, Thalidomide, Bortezomib
and/or autologous stem cell transplantation (ASCT) and in treatment with Rd.

- Patient is, in the investigator(s) opinion, willing and able to comply with the
protocol requirements.

- Patient has given voluntary written informed consent before performance of any
study-related procedure not part of normal medical care, with the understanding that
consent may be withdrawn by the patient at any time without prejudice to their future
medical care.

- Female patient is either post-menopausal or surgically sterilized or, if at
childbearing potential, must: understand that the study medication could have an
expected teratogenic risk.

- Agree to use, and be able to comply with, effective contraception without
interruption, 4 weeks before starting study drug, throughout study drug therapy
(including dose interruptions) and for 4 weeks after the end of study drug therapy,
even if she has amenorrhea. This applies unless the subject commits to absolute and
continued abstinence confirmed on a monthly basis. The following are effective methods
of contraception*:

- Implant**

- Levonorgestrel-releasing intrauterine system (IUS)**

- Medroxyprogesterone acetate depot

- Tubal sterilisation

- Sexual intercourse with a vasectomised male partner only; vasectomy must be
confirmed by two negative semen analyses

- Ovulation inhibitory progesterone-only pills (i.e., desogestrel)

- Combined oral contraceptive pills are not recommended. If a subject was using combined
oral contraception, she must switch to one of the methods above. The increased risk of
venous thromboembolism (VTE) continues for 4 to 6 weeks after stopping combined oral
contraception.

- **prophylactic antibiotics should be considered at the time of insertion particularly
in patients with neutropenia due to risk of infection.

- Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25
mills International Units on milliliter (mIU/ml) not more than 3 days before the start
of study medication once the subject has been on effective contraception for at least
4 weeks. This requirement also applies to women of childbearing potential who practice
complete and continued abstinence.

- Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks
after the end of study treatment, except in the case of confirmed tubal sterilization.
These tests should be performed not more than 3 days before the start of next
treatment. This requirement also applies to women of childbearing potential who
practice complete and continued abstinence.

- † A female subject or a female partner of a male subject is considered to have
childbearing potential unless she meets at least one of the following criteria: Age

≥50 years and naturally amenorrhoeic for ≥ 1 year (amenorrhoea following cancer
therapy does not rule out childbearing potential), premature ovarian failure confirmed
by a specialist gynaecologist, previous bilateral salpingooophorectomy or
hysterectomy, xy genotype, Turner's syndrome or uterine agenesis.

- Male subjects must:

- Agree to use condoms throughout study drug therapy, during any dose interruption
and for one week after cessation of study therapy if their partner is of
childbearing potential and has no contraception.

- Agree not to donate semen during study drug therapy and for one week after end of
study drug therapy.

- All subjects must:

- Agree to abstain from donating blood while taking study drug therapy and for one
week following discontinuation of study drug therapy.

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

- Patient who obtain at least a SD with Rd treatment and experienced a biochemical
progression without CRAB, during the treatment itself.

- Patient has a Karnofsky performance status ≥ 60%.

- Patient has a life-expectancy > 6 months.

- Patients must have a adequate cardiac function.

- Patients must have adequate pulmonary function.

- Patient has the following laboratory values within 14 days before Baseline (day 1 of
the Cyclophosphamide):

- Platelet count ≥ 50 x 109/L or ≥ 25 109/L if bone marrow involvement is ≥ 50% of
plasma cells in bone marrow biopsy.

- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L or ≥ 0,5 109/L x if bone marrow
involvement is ≥ 50% of plasma cells in bone marrow biopsy.

- Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L).

- Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal (ULN).

- Alanine transaminase (ALT): ≤ 2.5 x the ULN.

- Total bilirubin: ≤ 1.5 x the ULN.

- Calculated or measured creatinine clearance: ≥ 30 mL/minute.

Exclusion Criteria:

- Patients with newly diagnosed multiple myeloma.

- Patients who relapsed from multiple myeloma with signs of organ damage related to
disease (CRAB).

- Any serious medical condition, including the presence of laboratory abnormalities,
which places the subject at an unacceptable risk if he or she participates in this
study or confounds the experimental ability to interpret data from the study.

- Pregnant or lactating females.

- Prior history of malignancies, other than multiple myeloma, unless the subject has
been free of the disease for ≥ 3 years. Exceptions include the following: Basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the
cervix, carcinoma in situ of the breast, incidental histological finding of prostate
cancer (TNM stage of T1a or T1b).