Impact of Recombinant Human Interleukin-7 (CYT107) on Tumor Clearance and Immune Reconstitution in Multiple Myeloma Patients After Autologous Hematopoietic Cell Transplant

The Washington University

Status and phase: Enrolling; Phase 1

Conditions: Multiple Myeloma

Treatments: Procedure: Autologous hematopoietic cell transplant; Drug: Melphalan; Drug: Recombinant glycosylated human interleukin-7

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06523699

202412127

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

CYT107 + Melphalan + AHCT

Experimental group

Description:

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.

Treatment:

Drug: Recombinant glycosylated human interleukin-7

Drug: Melphalan

Procedure: Autologous hematopoietic cell transplant

Melphalan + AHCT

Active Comparator group

Description:

All patients on this protocol will be treated with standard of care melphalan conditioning followed by autologous hematopoietic stem cell transplant (AHCT).

Treatment:

Drug: Melphalan

Procedure: Autologous hematopoietic cell transplant