Multiple Myeloma
Conditions
Keywords
Myeloma, Immune reconstitution, IL-7, Cytokine, Autologous, Transplant
Brief summary
This is a two-arm, open-label, randomized, single-site, pilot study testing the addition of CYT107 following autologous hematopoietic cell transplant (AHCT) in patients with multiple myeloma (MM). The hypothesis of this study is that recombinant human CYT107 can be safely administered after AHCT and will promote quantitative and qualitative T cell reconstitution, which will be associated with enhanced tumor cell clearance and reduced infectious complications. Patients will be randomized to either the intervention arm that will receive CYT107 + standard of care melphalan and AHCT or to the control arm that will receive standard of care melphalan and AHCT only.
Interventions
DRUGRecombinant glycosylated human interleukin-7
Provided by RevImmune
DRUGMelphalan
Standard of care
Standard of care
Sponsors
Washington University School of Medicine
Revimmune
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized 2:1 to receive CYT107 + standard of care melphalan and AHCT or standard of care melphalan and AHCT alone.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of multiple myeloma per IMWG criteria. * Patient must be in first CR (including CR or sCR) or have PR or VGPR per IMWG criteria. * Patient must be candidate for melphalan and AHCT in the opinion of the treating physician. * At least 18 years of age. * ECOG performance status ≤ 2 * Adequate bone marrow and organ function as defined below: * Total bilirubin ≤ 2 x IULN * AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN * Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault * The effects of CYT107 on the developing human fetus are unknown. For this reason and also because many alkylating agents such as melphalan are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for one year post-transplant. Should a woman become pregnant or suspect she is pregnant, or a male suspect he has fathered a child during this time frame, s/he must inform the treating physician immediately. * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion criteria
* High doses of corticosteroids (greater than 5 mg prednisone equivalent daily) within 2 weeks of Day -2, with exception of premedication as needed for mobilization regimen. * A history of T-cell malignancy, plasma cell leukemia, or amyloidosis, or history of any other malignancy with the exceptions of in situ carcinomas, non-melanoma skin cancers, and malignancies for which all treatment was completed at least 2 years before Day -2 and the patient has no evidence of disease. * Currently receiving any other investigational agents. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CYT107, melphalan, or other agents used in the study. * Azathioprine, methotrexate, and anti-tumor necrosis factor agents within 2 weeks of Day -2. * A history of congenital immunodeficiency syndrome or autoimmune disease. Patients with autoimmune disorders adequately controlled with medication (5 mg prednisone equivalent or less) are allowed. * A history of clinically-significant pulmonary disorders, such as severe asthma, severe COPD, restrictive lung disease, pulmonary embolism within 3 months prior to study enrollment, or active or prior interstitial lung disease/pneumonitis. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. * Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of Day -2. * Patients without a backup autologous stem cell graft available.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of non-hematologic grade ≥3 CYT107 treatment-related AEs (excluding expected transplant-related AEs or AEs attributed to melphalan and ASCT) according to CTCAE v5 | Through day 365 | Treatment-related AEs will be defined as AEs occurring that are at least possibly related to the CYT107 treatment, or the combination of melphalan, AHCT, and CYT107. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of minimal residual disease (MRD) | At Day 100 | For the purposes of this study, a patient will be considered as having minimal residual diseases if a positive result (per 10-5 threshold) is obtained using the Adaptive Clonoseq MRD testing. |
| Rate of response by IMWG of ≥ complete response (CR) | At Day 100 | * Stringent complete response (sCR): * CR as defined below * Normal free light chain ratio (0.26-1.65) * Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence * Complete response (CR): * Negative immunofixation on the serum and urine * \<5% plasma cells in the bone marrow aspirate * Disappearance of any soft tissue plasmacytomas |
| Rate of ≥ grade 3 infections | Through day 365 | — |
| Days from transplant until absolute neutrophil count (ANC) engraftment | Through Day 30 | Neutrophil engraftment is defined as the first day of 3 consecutive days of ANC ≥ 500 following the post-transplant nadir. |
| Feasibility of treatment schedule | 1 month post-transplant (transplant is on Day 0) | The study will be feasible if 20% of patients are able to receive all 5 doses of CYT107 within the first month post-transplant. |
| Absolute lymphocyte count (ALC) recovery from pre-AHCT | Through Day 30 | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDilan A Patel, M.D.
Washington University School of Medicine
Outcome results
None listed