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

NCT02342613 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: J1484IRB00039074P01CA153962
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematologic Malignancies; Graft-Versus-Host Disease

Outcome Measures

Primary Outcomes (1)

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

  Feasibility is measured as the number of participants who achieve: 1) The successful obtaining of PTCy-MILs; 2) The expansion of PTCy-MILs to at least 70% of the assigned dose level; 3) Successful infusion of PTCy-MILs; 4) The absence of grade III-IV acute graft-versus-host-disease (GVHD) for 90 days after PTCy-MILs infusion. Acute GVHD is defined by the Modified Keystone Criteria.

  90 days

Secondary Outcomes (6)

• Optimal safe dose for PTCy-MILs

  90 days

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

  up to 3 years

• Number of participants who experience chronic GVHD

  up to 2 years post-transplant

• Clinical Response

  up to 3 years

• Progression-Free Survival

  up to 3 years

Study Arms (1)

MILs treatment

EXPERIMENTAL

Patients treated with the activated PTCy-MILs

Biological: Activated PTCy-MILs

Interventions

Activated PTCy-MILs 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.

MILs treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Graft vs Host Disease

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases

Study Officials

• Philip Imus, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2015
• First Posted: January 21, 2015
• Study Start: May 28, 2015
• Primary Completion: November 29, 2023
• Study Completion: March 31, 2024
• Last Updated: January 7, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)