- Subjects must have undergone a prior ASCT for multiple myeloma and have progressed
within 365 days of stem cell infusion. Progression is defined according to IMWG
- Prior ASCT must have utilized melphalan conditioning at a dose of 200 mg/m2.
- Patients who underwent syngeneic transplant (i.e., transplant from an identical
twin donor) rather than autologous transplant are eligible if syngeneic stem
cells are available for use in the salvage transplant and syngeneic transplant
will be considered equivalent to ASCT for the purposes of these
- Patients in whom first progression is identified between days 366 and 450
(inclusive) after ASCT will be eligible if progression is identified on their
first evaluation for progression in this window and if they had not been
evaluated between days 270 and 365 for progression. This clause is to account for
practice patterns in which patients otherwise doing well are monitored
infrequently (every 3-6 months) for relapse after they recover from their first
ASCT. This will allow infrequently monitored patients to be included if
progression is identified on their "12 month follow-up evaluation" if this
appointment happens to be scheduled just outside the 365-day post-ASCT window.
- There is no requirement that patients must enroll within 365 days of prior ASCT,
and patients may be treated with other agents, including experimental agents,
following relapse/progression after prior ASCT before enrollment on this study.
- Subjects must have received as part of their initial therapy for multiple
myeloma, prior to first ASCT, a regimen containing either bortezomib or
- Subjects must have signed written, informed consent.
- Subjects must be ≥ 18 and ≤ 70 years of age.
- Subjects must have adequate vital organ function to undertake ASCT, defined as the
- Estimated or measured creatinine clearance of ≥60 mL/min. CKD-EPI equation will
be used for estimation of creatinine clearance
- SGOT ≤ 3x the upper limit of normal and total bilirubin ≤ 2.0 mg/dl (except for
patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome).
- Left ventricular ejection fraction ≥45% as measured by echocardiography or MUGA
- Adequate pulmonary function with FEV1, FVC, TLC, and DLCO (after appropriate
adjustment for lung volume and hemoglobin concentration) ≥40% of predicted
- Non-hematologic toxicities from prior therapies must have recovered to grade ≤2
according to CTCAE 4.0 criteria or the subject's prior baseline.
- Subjects must have measurable disease, as defined in the IMWG response criteria49, on
- Subjects must have an ECOG performance status of 0-2 unless a higher performance
status is due solely to bone pain.
- Subjects must have stored in usable condition for second ASCT, as judged by the
principal investigator, ≥3x106 CD34+ cells per kg of body weight (either autologous or
syngeneic) stored in at least two bags such that after administration of the minimum
dose of 2 x 106 CD34+ cells/kg required on this protocol that a separate aliquot of at
least 1 x 106 CD34+ cells/kg remains for rescue infusion in the event of graft
- Subjects must agree not to attempt to become pregnant or impregnate others (e.g.,
through sexual intercourse or sperm donation) between enrollment and completion of
blinatumomab therapy. Sexually active subjects with reproductive potential must agree
during the study to utilize a reliable method of contraception, which may include
condoms (male or female), diaphragm or cervical cap with spermicide, intrauterine
device, or hormonal contraceptive. Acceptable documentation of the absence of
reproductive potential may consist of any one of the following: (1) physician
report/letter, (2) operative report or other source documentation of surgical
sterilization, (3) laboratory report of azospermia (required to document successful
vasectomy), (4) follicle stimulating hormone measurement elevated in the menopausal
- Due to the potential for neurological events, including seizures, while receiving
blinatumomab, subjects must be willing and able to refrain from driving and engaging
in hazardous occupations or activities such as operating heavy or potentially
dangerous machinery during the periods of blinatumomab infusion.
- Pregnant or lactating. Female subjects of reproductive potential (women who have
reached menarche and who have had menses within the preceding 24 months or have not
undergone hysterectomy or bilateral oophorectomy) must have a negative serum pregnancy
test performed at the time of screening.
- Active and uncontrolled infection
- Positive serum testing for hepatitis B core antibody or hepatitis B surface antigen.
- Evidence of active hepatitis C or HIV infection (positive serology with appropriate
positive confirmatory testing, such as nucleic acid-based testing).
- Any condition that would preclude participation as outlined in the judgment of the
- Prior allogeneic stem cell transplantation.
- Prior receipt of >1 autologous stem cell transplantation.
- Clinically significant CNS pathology, including documented or suspected CNS myeloma.
Clinically insignificant clinical examination findings or imaging abnormalities (e.g.,
age-related changes) should not be cause for exclusions of potential subjects.
- Class III/IV cardiovascular disability according to the New York Heart Association