T-Reg Cell Kinetics, Stem Cell Transplant, REGALE (REGALE)

March 24, 2016 updated by: Robert Krance, Baylor College of Medicine

T-Regulatory Cell Kinetics for Patients Receiving Alemtuzamb and Undergoing Stem Cell Transplantation From HLA Mismatched-Related, or HLA Matched, or One Antigen Mismatched-Unrelated Donors

Patients have a type of blood cell disorder that is very hard to cure. We are now suggesting a treatment that might help patients live longer without disease than other treatment plans would. This treatment is known as a stem cell transplant. We believe this may help patients as it allows us to give much stronger doses of drugs and radiation to kill the diseased cells than we could give without the transplant. We also think that the healthy cells may help fight any diseased cells left after the transplant.

Stem Cells are special "mother" cells that are found in the bone marrow (the spongy tissue inside bones), although some are also found in the bloodstream (peripheral blood). As they grow, they become either white blood cells which fight infection, red blood cells which carry oxygen and remove waste products from the organs and tissues or platelets, which enable the blood to clot. For the transplant to take place, we will collect these stem cells from a "donor" (a person who agrees to donate these cells) and give them to recipient. Patients do not have a sibling that is a perfect match, so the stem cells will come from a donor who is the best match available. This person may be a close relative or an unrelated person whose stem cells best "matches" the patients, and who agrees to donate stem cells. Before the transplant, two very strong drugs plus total body irradiation will be given to the patient (pre-conditioning). This treatment will kill most of the blood-forming cells in the bone marrow. We will then give the patient the healthy stem cells. Once these healthy stem cells are in the bloodstream they will move to the bone marrow (graft) and begin producing blood cells that will eventually mature into healthy red blood cells, white blood cells and platelets.

This research study will also use CAMPATH-1H as a pre-treatment. CAMPATH-1H is an antibody against certain types of blood cells. CAMPATH-1H is important because it stays active in the body for a long time after infusion, which means it may work longer at preventing GvHD symptoms.

The stem cell transplant described above is considered to be "standard" treatment. We would like to collect additional blood as described below in order to evaluate how the immune system is recovering.

We are asking permission to draw blood from the patient so that we can measure the number of certain blood cells called T regulatory cells. T regulatory cells are special immune cells that can control or regulate the body's immune response. We want to determine whether T regulatory cells are important participants in graft versus host disease (GVHD), infection and relapse. In GVHD, certain cells from the donated marrow or blood (the graft) attack the body of the transplant patient (the host). GVHD can affect many different parts of the body. The skin, eyes, stomach and intestines are affected most often. GVHD can range from mild to life-threatening. We do not know whether T regulatory cells can modify these conditions. We want to measure these T regulatory cells and learn if these cells do influence these conditions. If we learn that T regulatory cells do affect these conditions, then it may be possible to modify these cells for the benefit of transplant patients.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

To participate in this transplant, the patient will need to have a central line.

Before the transplant we will test the blood for viruses which can cause problems after the transplant. These viruses include Hepatitis B, cytomegalovirus and HIV. If the patient is positive for the AIDS virus, they will not be able to undertake the transplant.

Standard therapy: The patient will be given 6 doses of chemotherapy with a drug called Ara C in high doses (every 12 hours) which will begin 8 days before the stem cell transplant. Then, another chemotherapy drug called cyclophosphamide will be given in high doses by vein for two days on the 7th and 6th days before the transplant. A drug called MESNA will be given with cyclophosphamide. MESNA is used to decrease the side effects caused by cyclophosphamide. The patient will also receive an antibody called Campath (each day for 4 days before the transplant) to help destroy the immune system so that there is less host resistance to the growth of the donor cells. Radiation treatment will be given to the entire body on each day for 4 days before transplant. This will be given 2 times a day for 4 days. The chemotherapy and radiation treatment will last 8 days. If the patient has a diagnosis of T-cell Lymphoma, they will not be given the Ara-C.

Extra bone marrow tests may be recommended by the physician to check on the patients condition, especially if the marrow is slow to grow.

The day after the radiation treatment is completed; the patient will receive the healthy stem cells by vein. Once in the bloodstream, these stem cells will go to the bone marrow and should begin to grow.

In prevention of GvHD, the patient will also receive medicine called FK506 as well as low dose methotrexate. The FK506 will be given intravenously initially starting 2 days before the transplant and later by mouth (when they are able to take oral medications). This drug will be given each day for several weeks. Four doses of low dose methotrexate will be given intravenously. The methotrexate will be given on the day after the transplant, 3, 6 and 11 days after the transplant. If the GVHD cannot be controlled with FK506, other medicines may need to be given. The doctor will describe these medicines at that time.

Blood samples for research: To study how these cells are working in the patients system, blood samples will be taken each month for six months, at nine months, at one year, 2 years and 3 years following transplant. Approximately 6-8 teaspoons of blood will be collected each time. The total blood drawn for this study over three years should not exceed 1 and 3/4 cups. This amount is considered safe in adults. The amount of blood collected will be decreased in children and/or in patients where this amount of blood collection would not be appropriate.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Not Applicable

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
        • 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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

  • Patients with acute or chronic leukemia or advanced Hodgkin or non Hodgkin lymphoma or myelodysplastic/myeloproliferative disease who are unlikely to be cured by standard chemotherapy treatments. This includes patients who have relapsed after standard chemotherapy treatments and patients in first remission with unfavorable prognostic features.
  • Using the standard 6 HLA antigen profile (HLA class I, A and B, and HLA class II, DRB1) a patient must have either a one HLA antigen mismatched related donor or an HLA matched or one antigen mismatched unrelated donor.

EXCLUSION CRITERIA:

  • Patients with a life expectancy (less than or equal to 6 weeks) limited by disease other than leukemia.
  • Patients with symptomatic cardiac failure unrelieved by medical therapy or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction <20%).
  • Patients with severe renal disease (i.e., creatinine greater than 3 times normal for age).
  • Patients with pre-existing severe restrictive pulmonary disease (FVC less than 40% of predicted).
  • Patients with severe hepatic disease (direct bilirubin greater than 3 mg/dl or AST greater than 500 IU/L).
  • Patients with severe personality disorder or mental illness.
  • Patients with severe infection that in the estimation of the principal investigator prohibits the use of ablative chemotherapy.
  • Patients who are documented HIV positive.
  • Patients with a Karnofsky performance score <70% or Lansky score <50%.

NOTE: Patients who would be excluded from treatment on this protocol strictly for laboratory abnormalities can be included at the principal investigator's discretion after consultation with the members of the SCT Policy and Procedures Committee.

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: Stem Cell Transplant
All patients will receive Ara C IV every 12 hours for 6 doses starting at 1400 hours on day -8. Cyclophosphamide IV once daily on day -7 and day -6 starting at 1400 hours. MESNA will be administered 15 minutes prior to each dose of Cyclophosphamide and 3, 6, 9, and 12 hours after each dose of Cyclophosphamide. Campath 1h will be given on day -4, day -3, day -2 and day-1. TBI (Total Body Irradiation) will be delivered in 8 fractions of 1.75 Gy in two fractions on day -4, day -3, day -2, and day -1. Stem cell Infusion are infused on day 0.
Drug: ARA C
Ara C (3000 mg/m2) IV every 12 hours for 6 doses (days -8 to -5)
Other Names:
  • Cytarabine
Drug: Cyclophosphamide
Cyclophosphamide (45mg/kg) IV once daily on day -7 and day -6
Other Names:
  • Cytoxan
Drug: MESNA
MESNA (45mg/kg; divided into 5 doses) will be administered 15 minutes prior to each dose of Cyclophosphamide and 3, 6, 9, and 12 hours after each dose of Cyclophosphamide.
Other Names:
  • Mesnex
Radiation: Total Body Irradiation (TBI)
TBI: total dose 14.0 Gy, will be delivered in 8 fractions of 1.75 Gy in two fractions on day -4, day -3, day -2, and day -1
Other Names:
  • Radiation
Biological: Campath-1h
CAMPATH (3 mg IV for patients between 5 and 15 kg; 5 mg for patients between 16 and 30 kg; and 10 mg for patients greater than 30 kg) will be given on day -4, day -3, day -2 and day-1.
Other Names:
  • Alemtuzumab
Procedure: Stem Cell Infusion
Stem cells are infused on day 0

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Percentage of Treg Cells at 1 Year Post Transplant
Time Frame: 1 year
To define the biologic recovery and behavior of T regulatory cells for patients undergoing stem cell transplantation as specified in this protocol
1 year

Collaborators and Investigators

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

Sponsor

Baylor College of Medicine

Collaborators

Center for Cell and Gene Therapy, 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

October 1, 2007

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

December 19, 2007

First Submitted That Met QC Criteria

December 20, 2007

First Posted (Estimate)

December 21, 2007

Study Record Updates

Last Update Posted (Estimate)

April 22, 2016

Last Update Submitted That Met QC Criteria

March 24, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-21079-REGALE
  • REGALE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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