Sirolimus pre-conditioning before a T-cell engaging antibody in multiple myeloma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a Phase Ib, single-arm study at a single center with an expansion cohort. It aims to establish the safety and physiological effects of sirolimus given before Teclistamab or Talquetamab therapy in relapsed/refractory multiple myeloma patients previously exposed to T-cell engagers. After the initial dose-escalation/cohort phase, an expansion cohort will explore whether sirolimus pre-conditioning increases the Teffector:Texhausted T-cell ratio, potentially enhancing anti-tumor activity. The trial examines safety, tolerability, and preliminary efficacy signals of this sequencing strategy. Participants receive sirolimus followed by a T-cell engaging bispecific antibody regimen as part of the treatment plan.

Why it matters

Who can join: the full rules

Inclusion Criteria:

To be eligible to participate in this study, an individual must meet all of the following criteria:

* Willingness and ability to provide signed and dated informed consent form.
* Stated willingness to comply with all study procedures and availability for the duration of the study.
* Aged 18 years of older.
* Diagnosis with multiple myeloma, per IMWG Consensus Criteria.20
* Planned for treatment with teclistamab, or talquetamab per standard of care, label indications.15
* Prior exposure to any of the following types of T-cell engaging therapies.

  1. Anti-BCMA x CD3 bispecific antibody (for example: teclistamab, elranatamab)
  2. Anti-GPRC5d x CD3 bispecific antibody (for example: talquetamab)
  3. Anti-GPRC5d x CD3 x CD38 trispecific antibody
  4. Anti-BCMA x CD3 x CD38 trispecific antibody
  5. Anti-BCMA x CD3 x GPRC5d trispecific antibody
  6. Anti-BCMA chimeric antigen T-cell (for example: idecabtagene vicleucel, ciltacabtagene autoleucel)
  7. Anti-FcRL5 x CD3 bispecific antibody
* Required clinical laboratory values during screening phase

Hematologic Parameters Hemoglobin ≥7.0 g/dL; Platelets ≥25 x 109/L; Absolute Lymphocyte Count ≥0.2 x 109/L

Chemistries AST/ALT \< 5 x the ULN; Total Bilirubin \< 3 x the ULN

* Ability to take oral medication and be willing to adhere to the sirolimus pre-conditioning regimen.
* ECOG performance status of 0, 1, or 2 (KPS of \>50).
* For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner per section5.3.
* Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

* Participants whose multiple myeloma is progressing at a rapid pace requiring immediate anti-myeloma therapy per assessment by the principal investigator or enrolling investigator are excluded.
* Excluded concomitant medication exposures:

  * Exposure to corticosteroids within 1 week of treatment start
  * Exposure to calcineurin inhibitor or mTOR inhibitors (tacrolimus, everolimus, temsirolimus, sirolimus)
  * Immunomodulatory monoclonal antibodies targeting tumor necrosis factor alpha (e.g. infliximab), interleukin 6 (e.g. siltuximab),
  * Janus kinase inhibitors (e.g. ruxolitinib)
  * Any other investigational drug within 28 days
* History of allogeneic hematopoietic cell transplantation.
* Excluded concurrent medical conditions:

  * Active uncontrolled infection within 7 days prior to treatment start
  * Uncontrolled thrombotic event within 3 months of treatment start
  * Acute myocardial infarction or acute coronary syndrome within 6 months of start of treatment
  * Uncontrolled inflammatory bowel disease
  * Active hepatitis B virus, hepatitis C virus, or Human Immunodeficiency Virus infection
  * Uncontrolled rheumatologic conditions
  * Use of ACE-inhibitor therapy within 1 week of treatment start

    * Patients found to be taking ace-inhibitor therapy during screening can be included if the ace-inhibitor is substituted for an angiotensin receptor blocking agent. (https://drug-interactions.medicine.iu.edu/main-table)
    * CYP3A4/p-gp inhibitors and inducers for 7 days prior to sirolimus doses and 7 days after sirolimus doses(see appendix A for list)
  * Any other current active malignancy or history of metastatic malignancy that has the potential to interfere with the safety or efficacy assessment of the investigational intervention
* Pregnancy or lactation.
* Known allergic reactions to study agent (sirolimus).

Where it's running

• University of Iowa Health Care
  Iowa City, Iowa, United States Recruiting

Study contacts

• Principal investigator: Christopher Strouse, MD — University of Iowa
• Study coordinator: Christopher Strouse, MD
• Email: christopher-strouse@uiowa.edu
• Phone: (319) 356-0489

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.