Clinical trial NCT02342613: 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
Official title: Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes Derived From Patients With Bone Marrow Relapse of Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide Graft-Versus-Host Disease Prophylaxis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hematologic Malignancies
Graft-Versus-Host Disease
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2015-01-21
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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
timeFrame: 90 days
Secondary outcomes:
measure: Optimal safe dose for PTCy-MILs
timeFrame: 90 days
measure: Immunologic characterization of the PTCy-MIL product before and after expansion
timeFrame: up to 3 years
measure: Number of participants who experience chronic GVHD
timeFrame: up to 2 years post-transplant
measure: Clinical Response
timeFrame: up to 3 years
measure: Progression-Free Survival
timeFrame: up to 3 years
measure: Overall Survival
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Philip Imus, MD
role: PRINCIPAL_INVESTIGATOR
References: