Adoptive Immunotherapy With Activated Marrow Infiltrating Lymphocytes and Cyclophosphamide Graft-Versus-Host Disease Prophylaxis in Patients With Relapse of Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation

NCT ID: NCT02342613

Last Updated: 2025-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-28
• Study Completion Date: 2024-03-31

Brief Summary

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.

Detailed Description

Primary Objectives:

1. Feasibility of generating activated PTCy-MILs in patients with relapsed disease involving the bone marrow.

2. Toxicity of PTCy-MILs, specifically the rate of grade III-IV acute GVHD within the first 90 days after PTCy-MIL infusion.

Secondary Objectives

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

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

3. Immune reconstitution after treatment with PTCy-MILs.

4. Incidence and severity of chronic GVHD.

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

6. Progression-free and overall survival.

Conditions

Hematologic Malignancies; Graft-Versus-Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MILs treatment

Patients treated with the activated PTCy-MILs

Group Type: EXPERIMENTAL

Activated PTCy-MILs

Intervention Type: BIOLOGICAL

The activated PTCy-MILs will be infused through standard blood tubing containing a 170-260 micron filter without an additional leukoreduction filter into a central IV site. Each of the bags will be infused at a rate of approximately 10 ml per minute. The IV line will be flushed with normal saline immediately after completion of PTCy-MILs infusion to ensure that all product has been infused into the patient.

Interventions

Activated PTCy-MILs

The activated PTCy-MILs will be infused through standard blood tubing containing a 170-260 micron filter without an additional leukoreduction filter into a central IV site. Each of the bags will be infused at a rate of approximately 10 ml per minute. The IV line will be flushed with normal saline immediately after completion of PTCy-MILs infusion to ensure that all product has been infused into the patient.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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/ oncologist.

Exclusion Criteria

• 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 GVHD.
• 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 PTCy-MILs

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip Imus, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

IRB00039074

Identifier Type: OTHER

Identifier Source: secondary_id

P01CA153962

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

J1484

Identifier Type: -

Identifier Source: org_study_id