Clinical Trials /

Pilot Study of Blinatumomab in Combination With Salvage Autologous Stem Cell Transplantation for Patients With Refractory Multiple Myeloma

NCT03173430

Description:

This study involves receiving blinatumomab after high-dose melphalan and ASCT for multiple myeloma. The main purpose of this study is to: - To determine whether blinatumomab is safe and feasible to administer after ASCT in patients with advanced multiple myeloma. - To assess how long multiple myeloma remains under control when blinatumomab is administered after second ASCT.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Terminated

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study of Blinatumomab in Combination With Salvage Autologous Stem Cell Transplantation for Patients With Refractory Multiple Myeloma
  • Official Title: Pilot Study of Blinatumomab in Combination With Salvage Autologous Stem Cell Transplantation for Patients With Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: UPCC 56416
  • NCT ID: NCT03173430

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
BlinatumomabArm 1

Purpose

This study involves receiving blinatumomab after high-dose melphalan and ASCT for multiple myeloma. The main purpose of this study is to: - To determine whether blinatumomab is safe and feasible to administer after ASCT in patients with advanced multiple myeloma. - To assess how long multiple myeloma remains under control when blinatumomab is administered after second ASCT.

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalAn evaluable subject is any subject who completes two 28-day cycles of blinatumomab or discontinues blinatumomab after completion of less than one cycle due to toxicity.
  • Blinatumomab

Eligibility Criteria

        Inclusion Criteria:

          -  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
             criteria49.

               -  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
                  inclusion/exclusion criteria.

               -  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
                       lenalidomide.

          -  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
             following:

               -  Estimated or measured creatinine clearance of ≥60 mL/min. CKD-EPI equation will
                  be used for estimation of creatinine clearance
                  (http://www.kidney.org/professionals/kdoqi/gfr_calculator).

               -  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
                  scan.

               -  Adequate pulmonary function with FEV1, FVC, TLC, and DLCO (after appropriate
                  adjustment for lung volume and hemoglobin concentration) ≥40% of predicted
                  values.

               -  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
             study entry.

          -  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
             failure.

          -  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
             range.

          -  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.

        Exclusion Criteria:

          -  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
             principal investigator.

          -  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
             Classification.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Adverse Events
Time Frame:18 months
Safety Issue:
Description:

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

Last Updated

April 12, 2019