T-Reg Cell Kinetics, Stem Cell Transplant, REGALE

NCT00578539 | Terminated Results DMC

• 2 other identifiers: H-21079-REGALEREGALE
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia; Hodgkin Lymphoma; Non Hodgkin Lymphoma; Myeloproliferative Disorders

Keywords

Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Median Percentage of Treg Cells at 1 Year Post Transplant

  To define the biologic recovery and behavior of T regulatory cells for patients undergoing stem cell transplantation as specified in this protocol

  1 year

Study Arms (1)

Stem Cell Transplant

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: MESNA; Radiation: Total Body Irradiation (TBI); Biological: Campath-1h; Procedure: Stem Cell Infusion

Interventions

ARA C DRUG

Ara C (3000 mg/m2) IV every 12 hours for 6 doses (days -8 to -5)

Also known as: Cytarabine

Stem Cell Transplant

Cyclophosphamide DRUG

Cyclophosphamide (45mg/kg) IV once daily on day -7 and day -6

Also known as: Cytoxan

Stem Cell Transplant

MESNA DRUG

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.

Also known as: Mesnex

Stem Cell Transplant

Total Body Irradiation (TBI) RADIATION

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

Also known as: Radiation

Stem Cell Transplant

Campath-1h BIOLOGICAL

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.

Also known as: Alemtuzumab

Stem Cell Transplant

Stem Cell Infusion PROCEDURE

Stem cells are infused on day 0

Stem Cell Transplant

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Cohen JI, Jaffe ES, Dale JK, Pittaluga S, Heslop HE, Rooney CM, Gottschalk S, Bollard CM, Rao VK, Marques A, Burbelo PD, Turk SP, Fulton R, Wayne AS, Little RF, Cairo MS, El-Mallawany NK, Fowler D, Sportes C, Bishop MR, Wilson W, Straus SE. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood. 2011 Jun 2;117(22):5835-49. doi: 10.1182/blood-2010-11-316745. Epub 2011 Mar 31.

  PMID: 21454450 DERIVED

MeSH Terms

Conditions

Leukemia; Hodgkin Disease; Lymphoma, Non-Hodgkin; Myeloproliferative Disorders

Interventions

Cytarabine; Cyclophosphamide; Mesna; Whole-Body Irradiation; Radiation; Alemtuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Radiotherapy; Therapeutics; Investigative Techniques; Physical Phenomena; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Robert Krance, MD
• Organization: Baylor College of Medicine

rakrance@txch.org

832-824-4661

Study Officials

• Robert Krance, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Study Start: October 1, 2007
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: April 22, 2016
• Results First Posted: September 8, 2014

Record last verified: 2016-03

Locations

US (1)