Impact of Recombinant Human Interleukin-7 (CYT107) on Tumor Clearance and Immune Reconstitution in Multiple Myeloma Patients After Autologous Hematopoietic Cell Transplant
- Conditions
- Interventions
- Registration Number
- NCT06523699
- Lead Sponsor
- Washington University School of Medicine
- 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 reconstitu...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
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Histologically confirmed diagnosis of multiple myeloma.
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Patient must be in first CR (including CR or sCR) or have PR or VGPR per IMWG criteria.
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Patient must be candidate for melphalan and AHCT in the opinion of the treating physician.
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At least 18 years of age.
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ECOG performance status ≤ 2
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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
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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.
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Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
- High doses of corticosteroids (greater than 5 mg prednisone equivalent daily) within 2 weeks of Day -2.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CYT107 + Melphalan + AHCT Recombinant glycosylated human interleukin-7 All patients on this protocol will be treated with standard of care melphalan conditioning followed by autologous hematopoietic stem cell transplant (AHCT). After AHCT, if patients are randomized to the experimental arm, CYT107 will be initiated and will continue for 4 weeks. CYT107 will be administered subcutaneously starting on D+1. Two doses will be given during the first week, and then CYT107 will be administered weekly for 3 more weeks for a total of 5 doses. CYT107 + Melphalan + AHCT Melphalan All patients on this protocol will be treated with standard of care melphalan conditioning followed by autologous hematopoietic stem cell transplant (AHCT). After AHCT, if patients are randomized to the experimental arm, CYT107 will be initiated and will continue for 4 weeks. CYT107 will be administered subcutaneously starting on D+1. Two doses will be given during the first week, and then CYT107 will be administered weekly for 3 more weeks for a total of 5 doses. CYT107 + Melphalan + AHCT Autologous hematopoietic cell transplant All patients on this protocol will be treated with standard of care melphalan conditioning followed by autologous hematopoietic stem cell transplant (AHCT). After AHCT, if patients are randomized to the experimental arm, CYT107 will be initiated and will continue for 4 weeks. CYT107 will be administered subcutaneously starting on D+1. Two doses will be given during the first week, and then CYT107 will be administered weekly for 3 more weeks for a total of 5 doses. Melphalan + AHCT Melphalan All patients on this protocol will be treated with standard of care melphalan conditioning followed by autologous hematopoietic stem cell transplant (AHCT). Melphalan + AHCT Autologous hematopoietic cell transplant All patients on this protocol will be treated with standard of care melphalan conditioning followed by autologous hematopoietic stem cell transplant (AHCT).
- Primary Outcome Measures
Name Time Method Rate of non-hematologic grade ≥3 treatment-related AEs (excluding expected transplant-related AEs) 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 Outcome Measures
Name Time Method 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.
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
...Rate of ≥ grade 3 infections Through day 365 Absolute lymphocyte count (ALC) recovery from pre-AHCT Through Day 30 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.
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States