Clinical trial · Interventional

Infusion of Allogeneic, 3rd Party CD19-specific T Cells

Infusion of Allogeneic, 3rd Party CD19-specific T Cells for Patients With Refractory CD19+ B-Lineage Lymphoid Malignancies

NCT02274506CI-TRIAL-00042930withdrawnPhase 1ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Why stopped (as posted): PI's response to ePAAC, has withdrawn the protocol acknowledging the PI's action.

Summary

Brief summary (as posted)

The goal of this clinical research study is to learn if researchers can successfully and safely give patients who have had a stem cell transplant an infusion of white blood cells (called T-cells) that have been collected from an unrelated person, and that have been genetically changed. The process of changing the DNA (genetic material) of these T-cells is called "gene transfer." The gene transfer involves drawing blood from an unrelated donor, separating out T cells using a machine, changing the cells' DNA in the laboratory, and returning the genetically changed cells back to the body. T-cells are a type of white blood cell that fight infection. The type of gene transfer being used in this study is designed to help your T-cells to better fight cancer by targeting a chemical marker that is found on certain cancer cells. Researchers want to learn if these genetically-changed T-cells can help to control B-cell leukemia or lymphoma after a stem cell transplant. Researchers want to find out the highest tolerable dose of these T-cells that can be given to patients with relapsed leukemia or lymphoma.

Conditions

Conditions (3)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Blood And Marrow Transplantation	—	UNRESOLVED	—
Leukemia	Leukemia	ONTOLOGY_EXACT	0.90
Lymphoma	Lymphoma	ONTOLOGY_EXACT	0.90

Interventions

Interventions (3)

Intervention	Type	Mapped drug	Match
Cyclophosphamide	Drug	Cyclophosphamide	ALIAS
Fludarabine	Drug	Fludarabine	ALIAS
T-Cell Infusion	Procedure	—	UNRESOLVED

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
T-Cell Administration
description
Cyclophosphamide 60 mg/kg by vein for 2 consecutive days, followed by Fludarabine at 25 mg/m2/day by vein for 5 consecutive days. Fludarabine dose calculated per adjusted ideal body weight. T-cell product divided into 2 portions. Up to 25% of the genetically modified cells given on first day, with plan to infuse up to 75% of the remaining T-cell dose no sooner than 24 hours after completion of first portion. Second portion should not be given later than 72 hours after first portion. First group of 3 participants receive lowest dose of T-cells. Each new group receive a higher dose of T-cells than the group before it, if no intolerable side effects were seen. Up to 6 dose levels of T-cells will be tested.
interventionNames
1. Drug: Cyclophosphamide
2. Drug: Fludarabine
3. Procedure: T-Cell Infusion

Primary outcomes (1)

measure
Maximum Tolerated Dose (MTD) of CD19-Specific T Cells
timeFrame
12 hours
description
Maximum tolerated dose (MTD) is highest dose level 6 patients treated, with at most 2 experiencing dose limiting toxicity (DLT). DLT defined as new adverse event attributable to CD19-specific T cells of grade \>3 that lasts for more than 3 days, and related to CD19-specific T cells within 30 days of an infusion. Grade 3/4 graft versus host disease (GVHD) occurring within 6 weeks of CD19-specific T cells administration, also a DLT. Graft failure following CD19-specific T cells administration considered DLT.

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years
Maximum age: 70 Years

Show eligibility criteria text

Inclusion Criteria:

1. Patients with a history of refractory B-cell lymphoid malignancies: 1) acute lymphoblastic leukemia (ALL), CD19+, 2) biphenotypic leukemia CD19+, 3) non-Hodgkin's Lymphoma (NHL), which includes diffuse large B-cell lymphoma, small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, or chronic lymphocytic leukemia (CLL).
2. Age 18 to 70 years.
3. Zubrod performance 0-2 or Karnofsky greater than or equal to 60%.
4. Patient or patient's legal representative able to provide written informed consent.
5. Patient or patient's legal representative able to provide written informed consent for the long-term follow-up gene therapy study.
6. Patients must be a minimum of 3 months from last hematopoietic stem cell transplant (HSCT) and 3 weeks from last systemic chemotherapy.

Exclusion Criteria:

1. Patients with known allergy to bovine or murine products.
2. Clinically significant acute or chronic GVHD requiring systemic immunosuppression, including methylprednisolone \>/= 1 mg/kg/day.
3. Systemic corticosteroid use within 72 hours of treatment initiation.
4. Antibody to HLA expressed on 3rd party T cells.
5. Experiencing any new Grade \>2 (CTC version 4) adverse neurologic, pulmonary, cardiac, gastrointestinal, renal or hepatic (excluding albumin) event within 24 hours prior to treatment initiation.
6. Active infection defined as positive culture, if available, for bacteria, fungus, or virus within a 3-day period prior to treatment initiation and/or fever greater than 38°C within 24 hours prior to treatment initiation.
7. Positive beta HCG by qualitative pregnancy test in female of child-bearing potential defined as not post menopausal for 12 months or absence of previous surgical sterilization.

References

Publications (0)

Data not yet available

No reference posted for this study.