A Study Evaluating the Safety and Efficacy of KITE-585 in Subjects With Relapsed/Refractory Multiple Myeloma

Overview

About this study

To evaluate the safety and tolerability of KITE-585, an autologous engineered CAR T-cell product targeting a protein commonly found on myeloma cells called BCMA. Patients will be given a 3 day course of chemotherapy followed by a single infusion of KITE-585.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  1. Measurable relapsed or refractory myeloma as defined by the International Myeloma Working Group (IMWG) Consensus Criteria following treatment with at least 3 lines of therapy including with both a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or progressive myeloma that is refractory to a regimen containing both a PI and an IMiD.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  3. Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
    • Absolute neutrophil count (ANC) ≥ 1,000/µL
    • Platelet count ≥ 75,000/µL
    • Absolute lymphocyte count ≥ 100/µL
    • Creatinine clearance above limits set in the protocol for each cohort
    • Normal cardiac function as assessed by electrocardiogram (ECG) and echocardiogram
    • Baseline oxygen saturation > 92% on room air and no clinically significant pleural effusion

Exclusion Criteria:

  1. Plasma cell leukemia
  2. Non-secretory multiple myeloma
  3. History of CNS involvement by MM
  4. Prior CAR therapy or other genetically modified T cells
  5. Inadequate washout from prior therapy
  6. Autologous stem cell transplant within 6 weeks before enrollment or any history of allogenic transplant
  7. History of active autoimmune disease
  8. History of deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment
  9. Recent history of other (non multiple myeloma) cancer
  10. Active viral, fungal, bacterial or other infection

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

  • Despite advances in treatment, most patients with multiple myeloma (MM) will relapse, and long-term survival remains poor. B-cell maturation antigen (BCMA) is an ideal therapeutic target as it is expressed throughout the disease course with normal tissue expression limited to plasma and some B-cell lineages. This phase 1, multicenter, first-in-human study evaluated the safety and efficacy of KITE-585, an autologous anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory MM (RRMM). Key eligibility criteria included measurable MM and progression, defined by the International Myeloma Working Group Consensus Criteria within 60 days of the last treatment. Patients underwent leukapheresis and subsequently received a 3-day conditioning therapy regimen (cyclophosphamide [300 mg/m/day] and fludarabine [30 mg/m/day]). Patients then received a flat dose of 3 × 10 to 1 × 10 KITE-585 CAR T cells in a 3+3 dose-escalation design. The primary endpoint was incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs). Key secondary and exploratory endpoints included efficacy outcomes, incidence of AEs, levels of KITE-585 in blood, serum cytokines, and incidence of anti-BCMA CAR antibodies. Seventeen patients were enrolled, and 14 received KITE-585 with a median follow-up of 12.0 months. The median age of patients was 56 years, 41.2% had an Eastern Cooperative Oncology Group performance status of 1, 92.9% had baseline BCMA expression on plasma cells, and median number of prior therapies was 5.5. No patients experienced a DLT, all patients experienced ≥ 1 grade ≥ 3 treatment-emergent AE (TEAE), and no grade 5 TEAEs were observed. There were no grade ≥ 3 events of cytokine release syndrome, neurologic events, or infections; all were grade 1 or 2, and each occurred in 21.4% of patients. Among all patients infused with KITE-585, 1 patient who received 3 × 10 anti-BCMA CAR T cells experienced a partial response. Median peak CAR T-cell expansion was low (0.98 cells/μL), as were median peak serum levels of CAR-associated cytokines, including interferon-γ (61.45 pg/mL) and interleukin-2 (0.9 pg/mL). KITE-585 demonstrated a manageable safety profile; however, the limited CAR T-cell expansion and associated lack of anti-tumor response in patients with RRMM treated with KITE-585 is consistent with the minimal CAR T-cell activity observed. Read More on PubMed

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

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