Donor T Cells, Low-Dose Aldesleukin, and Low-Dose GM-CSF After Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

March 4, 2014 updated by: Barbara Ann Karmanos Cancer Institute

Immune Consolidation With Allogeneic Activated T Cells Armed With OKT3 x Rituxan (Anti-CD3 x Anti-CD20) Bispecific Antibody (CD20Bi) After Allogeneic Peripheral Blood Stem Cell Transplant for High Risk CD20+ Non-Hodgkin's Lymphoma (Phase I)

RATIONALE: Giving high doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. Colony stimulating factors, such as aldesleukin and GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells that have been treated with antibodies after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells given together with low-dose aldesleukin and low-dose GM-CSF after donor stem cell transplant in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose of donor-derived allogeneic anti-CD3 X anti-CD20 bispecific antibody (CD20Bi)-armed activated T cells (ATC) when given with low-dose aldesleukin and low-dose sargramostim (GM-CSF) after allogeneic stem cell transplantation in patients with relapsed or refractory CD20-positive non-Hodgkin lymphoma.
  • Perform trafficking studies using indium I 111-labeled unarmed ATC and ATC armed with CD20Bi in patients with evaluable lymphoma sites to determine whether armed ATC specifically traffic to tumor sites and correlate these data with CT and PET scans.
  • Evaluate immune responses and immune reconstitution of T and B cells.

OUTLINE: All patients receive high-dose chemotherapy that is standard of care for their disease. Peripheral blood lymphocytes are obtained from the HLA-identical sibling donor and cultured to obtain activated T cells (ATC), some of which are subsequently armed with CD20 bispecific antibody (CD20Bi) and cryopreserved for later use. Patients then undergo allogeneic hematopoietic stem cell transplantation (SCT).

Patients receive ATC-CD20Bi IV on days 40, 70, 100, 130, and 160 after SCT. Patients receive low-dose aldesleukin subcutaneously (SC) once daily for 7 days beginning within 24 hours after each ATC-CD20Bi infusion and low-dose sargramostim (GM-CSF) SC every other day for 3 doses beginning within 24 hours after each infusion of ATC-CD20Bi. Patients also receive tacrolimus and mycophenolate mofetil as standard graft-vs-host disease prophylaxis. Treatment continues in the absence of unacceptable toxicity.

Some patients with well-defined or evaluable masses receive indium I 111 (^111I)-labeled ATC-CD20Bi IV and ^111I-labeled unarmed ATC and then undergo whole-body imaging for trafficking studies.

After completion of study treatment, patients are followed at 6 months, 12 months, and then annually thereafter.

Study Type

Interventional

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed CD20-positive non-Hodgkin lymphoma

    • Relapsed, resistant, or chemorefractory disease
  • Must have an available HLA-identical sibling donor
  • No significant skin breakdown from tumor or other disease

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • DLCO ≥ 50% of normal
  • No symptomatic obstructive or restrictive pulmonary disease
  • Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min
  • Direct bilirubin ≤ 2.0 mg/dL (even if attributable to disease)
  • SGOT and SGPT ≤ 2.5 times normal (even if attributable to disease)
  • No history of severe hepatic dysfunction
  • No severe cardiac dysfunction
  • LVEF ≥ 50% by gated blood pool scan
  • No major heart disease
  • Patients with congenital or acquired heart disease or cardiac arrhythmias must undergo a cardiology consultation and evaluation

  • No active infections

    • Patients who have not been seen and evaluated by a dentist for teeth cleaning and examination for potential sources of infection are ineligible
  • HIV antibody negative
  • No uncompensated major thyroid or adrenal dysfunction
  • Not pregnant or nursing

  • Persistently elevated systolic blood pressure (BP) ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg must be controlled with antihypertensive agents for at least 7 days prior to initiation of cell therapy

    • Patients with essential hypertension that is controlled with medication are eligible

PRIOR CONCURRENT THERAPY:

  • Prior total dose of doxorubicin or daunorubicin must have been less than 450 mg/m^2 unless an endomyocardial biopsy shows less than grade 2 drug effect
  • No concurrent nitroglycerin preparations for angina pectoris
  • No antiarrhythmic drugs for major ventricular dysrhythmias

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival
Maximum tolerated dose
Disease-free survival
Time to relapse

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Lawrence G. Lum, MD, DSc, Barbara Ann Karmanos Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

July 1, 2008

Study Completion (Actual)

July 1, 2008

Study Registration Dates

First Submitted

August 24, 2007

First Submitted That Met QC Criteria

August 24, 2007

First Posted (Estimate)

August 27, 2007

Study Record Updates

Last Update Posted (Estimate)

March 5, 2014

Last Update Submitted That Met QC Criteria

March 4, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000561787
  • P30CA022453 (U.S. NIH Grant/Contract)
  • WSU-2007-034
  • 2365-1186500223.02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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