Activated Immune Cells in Treating Patients with Hematologic Cancers That Have Relapsed after Donor Stem Cell Transplant

This phase I trial studies a type of biological therapy that uses activated immune cells, called activated marrow infiltrating lymphocytes (aMILs), to treat patients with cancers of the blood or bone marrow that have returned after a stem cell transplant from a donor. aMILs are blood and bone marrow cells that are stimulated to react to certain proteins and grow and expand in the laboratory. This may cause the cells to target and kill cancer cells.

Inclusion Criteria

• INCLUSION CRITERIA FOR ENROLLMENT: Active relapse involving the bone marrow of a hematologic malignancy >= 6 months after allogeneic hematopoietic cell transplant (alloHCT) employing PTCy as GVHD prophylaxis
• INCLUSION CRITERIA FOR ENROLLMENT: Donor cluster of differentiation (CD)3+ chimerism >= 30% measured in peripheral blood or bone marrow
• INCLUSION CRITERIA FOR ENROLLMENT: Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky performance scale (KPS) >= 70%
• INCLUSION CRITERIA FOR ENROLLMENT: The patient has been off all immunosuppression for at least 2 weeks at the time of PTCy-MILs collection
• INCLUSION CRITERIA FOR ENROLLMENT: Expectation of ability to safely undergo salvage treatment appropriate for the patient’s malignant disease type
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Confirmation of active relapse involving the bone marrow of a hematologic malignancy >= 6 months after alloHCT employing PTCy as GVHD prophylaxis and more than 90 days after PTCy-MILs infusion
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Donor CD3+ chimerism >= 30% measured in peripheral blood or bone marrow
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky performance scale (KPS) >= 70%
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: No active acute infections
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: No requirement for systemic steroids
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: White blood cell count (WBC) >= 2,000/uL
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Absolute neutrophil count (ANC) >= 1,500/uL
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Platelets >= 100,00/uL (transfusions are permitted)
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Hemoglobin >= 9.0 g/dL (transfusions are permitted)
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: AST (aspartate aminotransferase) =< 3 x ULN
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: ALT (alanine aminotransferase) =< 3 x ULN
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Bilirubin =< 1.5 x ULN
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Serum creatinine =< 1.5 x ULN or creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula)
• INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Expectation of ability to safely undergo salvage treatment appropriate for the patient’s malignant disease type

Exclusion Criteria

• EXCLUSION CRITERIA FOR ENROLLMENT: Most recent alloHCT performed did not utilize PTCy GVHD prophylaxis
• EXCLUSION CRITERIA FOR ENROLLMENT: The presence of active GVHD requiring treatment
• EXCLUSION CRITERIA FOR ENROLLMENT: The use of immunosuppression for grade II-IV acute GVHD within 28 days prior to the infusion of PTCy-MILs
• EXCLUSION CRITERIA FOR ENROLLMENT: Creatinine >= 2.5 times the upper limit of normal (ULN)
• EXCLUSION CRITERIA FOR ENROLLMENT: Total bilirubin > 3 times the ULN
• EXCLUSION CRITERIA FOR ENROLLMENT: AST (aspartate aminotransferase)/ALT (alanine aminotransferase) > 3 times the ULN
• EXCLUSION CRITERIA FOR ENROLLMENT: Human immunodeficiency virus (HIV)-1/2 or human T-cell lymphotropic virus (HTLV)-1/2 positivity
• EXCLUSION CRITERIA FOR ENROLLMENT: The patient’s life expectancy is =< 90 days even with aggressive treatment and/or supportive care, as determined by the treating hematologist/oncologist
• EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: More than 2 years have elapsed since the patient’s initial PTCy-MILs infusion
• EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Most recent alloHCT performed did not utilize PTCy GVHD prophylaxis
• EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: The presence of active GVHD requiring treatment
• EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: The use of immunosuppression for grade II-IV acute GVHD within 28 days prior to the infusion of PTCy-MILs
• EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Creatinine >= 2.5
• EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Total bilirubin > 3 times the upper limit of normal (ULN)
• EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: AST (aspartate aminotransferase)/ALT (alanine aminotransferase) > 3 times the ULN
• EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: HIV-1/2 or HTLV-1/2 positivity
• EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: The patient’s life expectancy is =< 90 days even with aggressive treatment and/or supportive care, as determined by the treating hematologist/oncologist

PRIMARY OBJECTIVES:

I. Feasibility of generating activated marrow infiltrating lymphocytes (MILs) from patients previously treated with post-transplantation cyclophosphamide (PTCy) (PTCy-MILs) who have relapsed disease involving the bone marrow.

SECONDARY OBJECTIVES:

I. Determination of an optimal safe dose for PTCy-MILs.

II. Immunologic characterization of the PTCy-MIL product before and after expansion.

III. Immune reconstitution after treatment with PTCy-MILs.

IV. Incidence and severity of chronic graft-versus-host disease (GVHD).

V. Clinical responses (complete remissions, partial remissions, stable disease) as measured by criteria specific for the particular disease type.

VI. Progression-free and overall survival.

OUTLINE:

Patients receive PTCy aMILs intravenously (IV) on day 14 after salvage therapy. Beginning at day 90, patients that are found to be in relapse may receive a second dose of PTCy aMILs IV.

After completion of study treatment, patients are followed up at 9, 15, 18, 21, and 24 months.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Leo Luznik

• Primary ID J1484
• Secondary IDs NCI-2015-00990
• Clinicaltrials.gov ID NCT02342613