Donor Cord Blood T-Cell Infusion After Stem Cell Transplant in Treating Patients With Relapsed Hematological Malignancies

Phase I Study of Ex Vivo Expanded Donor Cord Blood T-Lymphocyte Infusion in Post-Transplant Relapsed Patients

This phase I trial studies the side effects and best dose of donor cord blood T-cells after stem cell transplant in treating patients with relapsed hematological malignancies. After umbilical cord blood transplant, stem cells are collected from the donor's cord blood and stored. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by treatment. Removing the T cells and treating them in the laboratory before infusing them in the patient may also help boost the patient's immune system.

Study Overview

• Status: Terminated
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm
• Intervention / Treatment: Biological: Aldesleukin; Procedure: Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion; Biological: Umbilical Cord Blood-Derived Lymphocyte Therapy

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and maximum tolerated dose (MTD) of infusion of ex vivo expanded cord blood T cells (CLI), in cord blood (CB) transplant recipients with relapsed hematological malignancies.

SECONDARY OBJECTIVES:

I. To determine the complete remission rate and overall response as a result of CLI infusion.

II. To determine the effect of CLI infusion on the chimerism. III. To evaluate the incidence rate and grade of acute graft-versus-host disease (GvHD) after CLI infusion.

IV. To determine the disease-free survival, cytopenia rate, relapse incidence after CLI infusion.

OUTLINE: This is a dose-escalation study of ex vivo-expanded T-cells.

Patients undergo ex vivo-expanded umbilical cord blood progenitor cell donor T cell infusion with aldesleukin 11-14 days after T-cell co-stimulation begins.

After completion of study treatment, patients are followed up for 100 days.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Umbilical cord blood (UCB) recipients with underlying hematological malignancies presenting with post-transplant relapse and have available approximately 400 microliter to 1 ml aliquots or CB wash from previous transplant
• UCB recipients with T-cell and/or overall chimerism value of less than 80%, in absence of relapse and have available approximately 400 microliter to 1 ml aliquots or CB wash from previous transplant
• Performance score of at least 80% by Karnofsky or performance status (PS) < 3 (Eastern Cooperative Oncology Group [ECOG]) (age >= 12 years), or Lansky Play-performance scale of at least 60% or greater (age < 12 years)
• Negative beta human chorionic gonadotropin (HCG) or urine test in females of childbearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization and willing to use an effective contraceptive measure while on the study
• Patient or patient's legal representative, parent(s) or guardian able to sign informed consent

Exclusion Criteria:

• Human immunodeficiency virus (HIV) positive (due to the extreme immunosuppressive nature of allogeneic stem cell transplant)
• Patients with active (untreated) central nervous system (CNS) disease
• Any active GVHD
• Active invasive infections
• Pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (T-cell infusion); Patients undergo ex vivo-expanded umbilical cord blood progenitor cell donor T cell infusion with aldesleukin 11-14 days after T-cell co-stimulation begins.

Biological: Aldesleukin; Undergo ex-vivo-expanded umbilical cord blood progenitor cell donor T-cell infusion with aldesleukin; Other Names: Proleukin; 125-L-Serine-2-133-interleukin 2; r-serHuIL-2; Recombinant Human IL-2; Recombinant Human Interleukin-2; Procedure: Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion; Undergo ex-vivo-expanded umbilical cord blood progenitor cell donor T-cell infusion with aldesleukin; Biological: Umbilical Cord Blood-Derived Lymphocyte Therapy; Undergo ex-vivo-expanded umbilical cord blood progenitor cell donor T-cell infusion with aldesleukin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) of ex vivo expanded T-cells defined as the highest dose for which the probability of toxicity is closest to 30% without exceeding 30%	Dose limiting toxicity is defined as grade IV graft-versus-host disease (GVHD), grades 3-4 acute GVHD occurring within 45 days of the study T cell infusion, grade 3-5 organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic), grade 4 cytopenia, or any grade 4 or 5 organ based (non-hematologic) toxicity.	Up to day 45

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events by grade by ex vivo expanded cord blood T cells dose and overall		Up to day 100
Numbers of patients treated at the MTD with grade 2-4 GVHD	Estimated with an exact 95% binomial confidence interval.	Up to day 100
Proportion of patients with remission post-infusion	Estimated with an exact 95% binomial confidence interval.	Up to day 100
Proportion of patients achieving chimerism post-infusion	Estimated with an exact 95% binomial confidence interval.	Up to day 100
Proportion of patients with cytopenia post-infusion	Estimated with an exact 95% binomial confidence interval.	Up to day 100
Proportion of patients that relapse after infusion	Estimated with an exact 95% binomial confidence interval.	Up to day 100
Disease-free survival	Estimated with the Kaplan-Meier product limit estimator.	Up to day 100

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sairah Ahmed, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2013
• Primary Completion (Actual): May 30, 2018
• Study Completion (Actual): May 30, 2018

Study Registration Dates

• First Submitted: June 26, 2012
• First Submitted That Met QC Criteria: June 26, 2012
• First Posted (Estimate): June 28, 2012

Study Record Updates

• Last Update Posted (Actual): November 13, 2018
• Last Update Submitted That Met QC Criteria: November 8, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Aldesleukin; Interleukin-2
• Other Study ID Numbers: 2011-1178 (Other Identifier: M D Anderson Cancer Center); P30CA016672 (U.S. NIH Grant/Contract); NCI-2013-00385 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No