Low Dose IL-2, Hematopoietic Stem Cell Transplantation, IL2 for GVHD (IL2 for GVHD)

April 3, 2018 updated by: Rayne Rouce, Baylor College of Medicine

Phase II Trial Using Low Dose IL-2 to Induce Regulatory T Cells in Patients After Allogeneic Hematopoietic Stem Cell Transplantation as Graft Versus Host Disease Prophylaxis

Patients are being asked to participate in this study because treatment for their disease requires a stem cell transplant (SCT). Stem cells are the source of normal blood cells found in the bone marrow and lead to recovery of blood counts after bone marrow transplantation. With stem cell transplants, regardless of whether the donor is a full match to the patient or not, there is a risk of developing graft-versus-host disease (GVHD).

GVHD is a serious and sometimes fatal side effect of SCT. GVHD occurs when the new donor stem cells (graft) recognizes that the body tissues of the patient (host) are different from those of the donor. When this happens, cells in the graft may attack the host organs. How much this happens and how severe the GVHD is depends on many things, including how different the donors cells are, the strength of the drugs given in preparation for the transplant, the quality of transplanted cells and the age of the person receiving the transplant.

Typically, acute GVHD occurs in the first 100 days following transplant, while chronic GVHD occurs after day 100. Acute GVHD most often involves the skin, where it can cause anywhere from a mild rash to complete removal of skin; liver, where it can anywhere from a rise in liver function tests to liver failure; and the gut, where it can cause anywhere from mild diarrhea to profuse, life-threatening diarrhea. Most patients who develop GVHD experience a mild to moderate form, but some patients develop the severe, life-threatening form.

Previous studies have shown that patients who receive SCT's can have a lower number of special T cells in their blood, called regulatory T cells, than people who have not received stem cell transplants. When regulatory T cells are low, there appears to be an increased rate of severe, acute GVHD. A drug known as IL-2 (Proleukin) has been shown to increase the number of regulatory T cells in patients following stem cell transplant, and in this study investigators plan to give low dose IL-2 after transplant.

This study is called a phase II study because its major purpose is to find out whether using a low-dose of IL-2 will be effective in preventing acute GVHD. Other important purposes are to find out if this treatment helps the patient's immune system recover regulatory T cells faster after the transplant. This study will assess the safety and toxicity of low-dose IL-2 given to patients after transplantation and determine whether this drug is helpful in preventing GVHD.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Participation in this protocol will last about 1 year.

To participate in this study, the patient will need to have undergone a stem cell transplant. Before the treatment starts, investigators would like to test the patient's blood blood for the number of regulatory T cells already present before beginning IL-2.

Treatment Plan:

Before the conditioning treatment for the transplant, 30 to 40 ml (6 to 8 teaspoonfuls) of blood will be collected from the patient for regulatory T cell analysis. Approximately same amount of blood will also be collected on day 0 (the day of the transplant), and at the following times after the transplant: day 7 (the day the IL-2 will most likely start) then weekly for another eleven weeks, then monthly for 8 months.

On approximately day 7 following the transplant, if the patient is well and meets the eligibility requirements, the IL-2 injections will begin. These will be given subcutaneously (as a small injection just under the skin) three times per week for 6 weeks. The injections may also been given through a special catheter, called an Insuflon catheter, that is placed just under the skin for a week at a time. The first dose must be given in the hospital, but the remaining doses can be given at home. The patient will be taught how to give the injections to him/ herself.

If the patient's body has no serious toxicities from the IL-2 and has not developed severe GVHD, the patient can continue to get the injections the same way for an additional 6 weeks. If at any time the patient develops severe GVHD or serious toxicity related to the IL-2,the injections will be stopped. If the patient's disease returns (relapse) or he or she does not engraft (accept the donor graft), the patient will be removed from the study.

The patient's labs will be followed closely while he/she is receiving the IL-2 injections, as well as heart, kidney and lung functions; however, these are all standard tests that the patient will receive after transplant regardless of participation in this study.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • The Methodist Hospital
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital

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

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

INCLUSION CRITERIA FOR INITIAL STUDY ENROLLMENT:

Patients will be eligible for initial enrollment on this study as long as they meet the following criteria:

  • Diagnosis of acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, myeloproliferative disorder, Hodgkin lymphoma, non-Hodgkin lymphoma or non-malignant disease requiring allogeneic HSCT
  • Birth to age 70 years of age
  • Study entry consent is signed and faxed to Research Coordinator

INCLUSION CRITERIA AT TIME OF IL-2 ADMINISTRATION:

  • At least day +7 post transplant
  • Less than or equal to 30 days post transplant
  • Lansky or Karnofsky score greater than or equal to 50%
  • Total bilirubin less than or equal to 1.5mg/dL
  • Alanine aminotransferase level (ALT) less than or equal to five times normal, serum direct bilirubin less than or equal to 1.5mg/dL, albumin greater than or equal to 3.0gm/dL
  • Serum creatinine less than three times normal or creatinine clearance greater than 80mg/min/1.73m2
  • Ensure that informed consent signed and faxed to Research Coordinator

EXCLUSION CRITERIA:

EXCLUSION CRITERIA AT TIME OF IL-2 ADMINISTRATION:

Patients will be ineligible to receive IL-2 injections if any of the following is true:

  • Active, acute GVHD greater than or equal to grade II
  • Serious, active bacterial, fungal or viral infection (i.e. intensive care)
  • Clinical Signs of severe pulmonary dysfunction
  • Clinical Signs of sever cardiac dysfunction
  • Receiving corticosteroids as GVHD treatment
  • Hypersensitivity or allergy to IL-2

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)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IL2 Administration

SCHEDULE OF IL-2 ADMINISTRATION: Patients will receive a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT.

Time will be measured as 'week beginning with first IL-2 injection.'

T cell Induction via IL-2 to reduce GVHD
Biological: IL-2

IL2 Administration:

Patients will be given a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. If the patient has not developed >grade I side effects to IL-2 and has not developed >grade I GVHD then the patient may continue the IL-2 for 6 additional weeks. Time will be measured as 'week beginning with first IL-2 injection.

Other Names:
  • Proleukin
  • Aldesleukin
  • Interleukin-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Dose Limiting Toxicities
Time Frame: 6-12 weeks
Assessment of the safety and the toxicity of low-dose IL-2, administered according to the dosage described in this protocol, in this group of patients The outcome measure is the proportion of participants with dose limiting toxicities.
6-12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Severe (Grade III or IV) Acute GVHD
Time Frame: Up to 12 weeks on low-dose IL-2
To determine the efficacy of low-dose IL-2 in the prevention of severe (grade III or IV) acute GVHD
Up to 12 weeks on low-dose IL-2
Percentage Change in CD4+ CD25+ FoxP3+ Regulatory T Cells (Tregs) From Pre to Post IL-2 Infusions
Time Frame: 12 weeks
To investigate the immunomodulatory effects of IL-2 administered after allogeneic hematopoietic stem cell transplantation
12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ancillary Studies
Time Frame: 12 weeks

To conduct ancillary studies on those patients to investigate before, during and after IL-2 administration to determine:

  • The immunophenotype of PBMCs
  • The suppressive activity of CD4+ CD25+ FoxP3+ Tregs
  • Cytokines secreted by PBMCs
  • NK cell analysis
12 weeks

Collaborators and Investigators

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

Sponsor

Baylor College of Medicine

Collaborators

The Methodist Hospital Research Institute
Center for Cell and Gene Therapy, Baylor College of Medicine

Investigators

  • Principal Investigator: Rayne Rouce, MD, Baylor College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

June 1, 2007

Primary Completion (Actual)

April 1, 2013

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

October 2, 2007

First Submitted That Met QC Criteria

October 2, 2007

First Posted (Estimate)

October 4, 2007

Study Record Updates

Last Update Posted (Actual)

May 4, 2018

Last Update Submitted That Met QC Criteria

April 3, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-20971-IL2 for GvHD
  • IL-2 for GVHD (Other Identifier: Baylor College of Medicine)

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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