This Phase 1 clinical study is designed to examine the safety and feasibility of using
anti-CD3/CD28 activated marrow infiltrating lymphocytes (MILs) as treatment of relapse after
allogeneic hematopoietic cell transplantation (alloHCT) for patients with hematologic
malignancies with bone marrow involvement of their relapsed disease. These MILs will be
derived from the bone marrow of the relapsed patient who had previously received
post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis
(PTCy-MILs). A bone marrow aspiration will be performed on the patient to collect ~200ml of
marrow for ex vivo expansion. During this expansion process, T cells will be activated and
expanded by co-stimulation with anti-CD3/anti-CD28 monoclonal antibodies covalently attached
to super-paramagnetic microbeads. Patients will be treated with salvage therapy while this
ex vivo expansion is ongoing. After the simultaneous salvage therapy and ex vivo expansion,
the activated PTCy-MILs will be reinfused. Patients will be monitored with the primary
objective being the feasibility of expanding to targeted dose levels activated PTCy-MILs
that do not cause grade III-IV acute GVHD within the first 90 days after PTCy-MIL infusion.
- Age ≥18 years old
- Bone marrow relapse of a hematologic malignancy ≥6 months after alloHCT using PTCy
- Donor CD3+ chimerism ≥ 30% measured in peripheral blood or bone marrow
- ECOG performance status ≤ 2 or Karnofsky performance scale ≥ 70%.
- Off all immunosuppressive drugs for 2 weeks prior to the PTCy-MILs collection.
- Expectation of ability to safely undergo salvage treatment appropriate for the
patient's malignant disease type as determined by the treating hematologist/
- Most recent alloHCT not utilizing PTCy.
- Active GVHD requiring treatment.
- Immunosuppression use within 28 days of PTCy-MIL infusion if prior grade II-IV acute
- Creatinine ≥ 2.5, total bilirubin > 3 times the upper limit of normal (ULN), or
AST/ALT > 3 times the ULN.
- HIV-1/2 or HTLV-1/2 positivity.
- Life expectancy ≤ 90 days even with aggressive treatment, as determined by the
treating hematologist/oncologist, which would preclude assessment of toxicity of