Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Micronutrients

Hematinics

Vitamins

Amino Acids

Fludarabine

Fludarabine phosphate

Methotrexate

Tacrolimus

Thymoglobulin

Busulfan

Antilymphocyte Serum

Imatinib Mesylate

Vidarabine

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

Calcineurin Inhibitors

Alkylating Agents

Antineoplastic Agents, Alkylating

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Folinic Acid

Folate

Vitamin B9

Tyrosine

Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m\^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m\^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.

Fludarabine (Fludara)

Antithymocyte Globulin (ATG)

Tacrolimus levels maintained between 5-15 ng/dl, first as continuous IV infusion, and converted to oral every 12 hour dosing as tolerated. Starting day -2 until day 180.

Infusion of lymphocytes from the original bone marrow donor by vein if relapse after \>4 weeks of imatinib.

Donor lymphocyte infusion (DLI)

Infusion of donor bone marrow or blood stem cells by vein over approximately one hour on day 0.

Stem Cell Transplant

Richard E. Champlin, MD

Primary Objective:

To estimate the probability of molecular complete remission at one year for the described sequential treatment approach, with nonablative hematopoietic transplantation, post transplant imatinib mesylate and donor lymphocyte infusion, in patients with Ph-positive Chronic Myelogenous Leukemia (CML) not in blastic transformation.

Secondary Objective:

Response to post transplant Imatinib mesylate therapy for 12 weeks as treatment of residual disease, response to donor lymphocyte infusion (DLI) for residual disease following imatinib mesylate therapy, as well as engraftment, toxicity, disease free survival and survival, effect of busulfan pharmacokinetics on study outcome.

Patients will have blood and bone marrow tests performed as well as chest and sinus X-rays and tests of their heart and lung function. Approximately 5 tablespoons of blood will be drawn.

All patients in this study will receive imatinib mesylate by mouth for 9 days, unless the patient is known to be allergic or have symptomatic intolerance to the drug, or if the leukemia has failed to respond to imatinib. Fludarabine 40 mg/m2 by vein for 4 days (days -5 to -2), busulfan 130 mg/m2 by vein for 2 days (days -3 and -2), and ATG (Antithymocyte Globulin) 2.5 mg/kg by vein for 3 days (-3,-2 and -1).

Patients will then receive the donor bone marrow or blood stem cells by vein over approximately one hour on day 0.

After the infusion of the donor cells, you will receive immunosuppressive therapy with tacrolimus and methotrexate to decrease the risk of developing graft-vs-host disease (GvHD).

Patients will need frequent blood tests to monitor their counts and blood chemistries. This is generally done daily while in hospital and at least twice per week for the first 100 days post transplant. You may need frequent blood transfusions and may have to be admitted to the hospital to receive antibiotics if they develop fever. Bone marrow will be examined frequently beginning four weeks after treatment to evaluate response to treatment; Blood and bone marrow exams are to be performed at one, two three, six, 12 and 18 months post transplant and yearly thereafter for 5 years. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.

Patients in whom treatment produces a remission, in which no sign of the leukemia can be detected, will receive no further therapy unless the leukemia recurs. Patients with evidence of leukemia after 3 months from the transplant will receive additional treatment with imatinib mesylate; those with detectable leukemia after an additional 3 months may receive an infusion of immune cells from the transplant donor.

If there is evidence of leukemia after the transplant, you will receive additional treatment with imatinib mesylate. If leukemia cells can still be detected, additional donor immune cells will be given to you by vein.

Patients are considered on the study for 5 years after the transplant.

A total of 90 patients will take part in this study. All will be enrolled at M. D. Anderson.

Imatinib Mesylate, Busulfan, Fludarabine, and Antithymocyte Globulin for CML Patients

Imatinib Mesylate, Busulfan, Fludarabine, Antithymocyte Globulin and Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia

Participants at 1 year in molecular remission, post transplant, post imatinib mesylate and donor lymphocyte infusion (DLI). Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests (this test is most commonly used in clinical trials).

Number of participants with response of molecular complete remission (mCR) to Imatinib Mesylate therapy as treatment for residual disease after transplant. Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests.

Number of participants with response of molecular complete remission (mCR) to DLI as treatment for residual disease after transplant. Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Mesylate, Busulfan, Fludarabine + Antithymocyte Globulin

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Study completed early due to support issues.

Richard E. Champlin, MD/Professor

Analysis was per protocol. Only 19 participants having the post transplant Imatinib Mesylate Therapy out of the 41 participants treated were analyzed for this outcome.

Participants' With mCR Response to Post Transplant Imatinib Mesylate Therapy

Analysis was per protocol. One patient did not receive treatment and was excluded from analysis.

Number of Participants in Complete Molecular Remission at 1 Year

Only 8 participants having the post-transplant DLI out of the 41 participants treated were analyzed for this outcome.

Participants' With mCR Response to Post Transplant DLI

Overall Study

Heart and Blood Diseases

Immune System Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Syndrome

Lymphoma

Hematologic Neoplasms

Anemia

Anemia, Aplastic

Graft vs Host Disease

Preleukemia

Myelodysplastic Syndromes

Primary Myelofibrosis

Lymphosarcoma

Aplastic Anemia

Homologous Wasting Disease

Visilizumab

Visilizumab, Tacrolimus and Methotrexate.

Second Stage: Antithymocyte-globulin (ATG), Tacrolimus and Methotrexate. The study was closed during first stage and did not proceed to the second stage comparison to ATG in combination with tacrolimus/methotrexate as originally planned.

3 mg/m\^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant).

0.02 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 4 after transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.

15 mg/m\^2 intravenously (IV) on Day 1 after transplant; 10 mg/m\^2 IV on Days 3, 6 and 11 after transplant.

1 mg/kg IV over 6 hours on Day 3 before transplant; 3.25 mg/kg IV over 4 hours on days 2 and 1 before transplant.

Antithymocyte globulin (ATG)

0.03 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 3 before transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.

15 mg/m\^2 IV on Day 1 after transplant; 10 mg/m\^2 IV on Days 3, 6 and 11 after transplant.

Lia Perez, MD

The purpose of this study was to test whether a new drug named visilizumab would decrease the severity of graft-versus-host disease in patients treated with a mismatched donor. Investigators planned to use visilizumab in combination with tacrolimus and methotrexate as the "study treatment".

The protocol plan was a two stage, controlled, phase II study to assess safety and compare the grade of acute graft-versus-host disease (GVHD) with visilizumab, or Anti-thymocyte Globulin (ATG) in combination with tacrolimus + methotrexate in patients at high risk of GVHD after transplant from unrelated donors mismatched for 1-2 alleles of any type at human leukocyte antigen (HLA) A, B, C and DRB1.

The study design included two stages. The first stage of the trial was to enroll 15 patients on a single arm to be treated with "study treatment" (visilizumab, tacrolimus and methotrexate) to assess for treatment safety and exclude intolerable GVHD. The second stage of the trial was to include a random control group of patients treated with the current "standard treatment" (ATG, tacrolimus, and methotrexate) or "study treatment". The purpose of this comparison was to determine if the "study treatment" visilizumab causes less severe side effects and if it is more potent in reducing graft-versus-host disease symptoms than the "standard treatment".

Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

A Phase II Study of Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

Cumulative Incidence of Grade II-IV Acute GVHD Score at 100 Days. Investigators had planned to assess whether the grade of acute GVHD was decreased by visilizumab in combination with tacrolimus/methotrexate compared to standard treatment with thymoglobulin/tacrolimus/methotrexate after transplantation from unrelated mismatched donors, from day of transplant up to one year. Study was closed during the first treatment stage and did not proceed to the second stage treatment comparison to ATG in combination with tacrolimus/methotrexate as originally planned.

Overall GVHD Grade: From Filipovich AH, Weisdorf D, Pavletic S, etal: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 11:945-955 (2005). Grade I: Skin Stage 1-2, Liver Stage 0, Gut State 0; Grade II: Skin Stage 3 or, Liver Stage 1 or, Gut Stage 1; Grade II

Number of participants who reactivated EBV. Patients had their plasma tested once weekly using the TaqMan polymerase chain reaction (PCR) for quantitative determination of EBV-DNA for 6 weeks. Plasma levels \> 1000 copies per ml plasma were scored as positive.

Participants who developed plasma EBV-DNA of \>1000 copies/mL on any tests received rituximab.

Incidence of Rituximab Response: Reactivated EBV participants whose plasma titers cleared after rituximab, without post-transplant lymphoproliferative disorder (PTLD).

Median OS in days. Survival was measured from the time of transplant to the time of death.

National Institutes of Health (NIH)

H. Lee Moffitt Cancer Center and Research Institute

The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.

Visilizumab, Tacrolimus and Methotrexate. All participants.

First Stage: Study Treatment

Age, Continuous

First Stage: Study Treatment. All participants.

Study closed early during the first stage, did not proceed to the second stage comparison as planned. Investigators exercised right to close the study prematurely for lack of efficacy, although no protocol-defined end points had been met.

Lia Perez, M.D.

Grade II-IV Acute GVHD

Grade I-II Acute GVHD

Grade III-IV Acute GVHD

First Study Stage: Study Treatment

Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days

Incidence of Epstein-Barr Virus (EBV) Reactivation

Incidence of Rituximab Response to Reactivated EBV Without PTLD

First Study Stage: Study Treatment. Visilizumab, Tacrolimus and Methotrexate.

2 Year Analysis Group

5 Year Analysis Group

Participants who had died by Year 2 and additional participants who had died by Year 5.

Overall Survival (OS)

Pharmacodynamics of Visilizumab - Test 1

Pharmacodynamics of Visilizumab - Test 2

Melphalan

Arm I contains fludarabine, melphalan, and antithymocyte globulin (ATG)

Arm II contains fludarabine, busulfan, antithymocyte globulin (ATG), and total body irradiation (TBI).

Melphalan is given daily for 2 days, overlapping with the completion of fludarabine.

Fludarabine is given through the vein daily for 5 days.

Total Body Irradiation (TBI)

Andrew Artz, MD

The primary objective of this study is to assess the rate of engraftment with combined haploidentical-cord blood transplantation in patients with pre-existing donor specific antibodies and in those with active disease.

Primary Objective

- To assess the rate of engraftment with combined haploidentical-cord blood transplantation in patients with pre-existing donor specific anti-HLA antibodies and in those with active disease

Secondary Objectives

* To determine the long term fate of the haplo transplant and the cord blood transplant in this setting.
* To describe the incidence and severity of acute and chronic GVHD.

Cord Blood Transplantation for Patients With Cancer

Combined Transplantation of Unmanipulated Haploidentical and a SingleCord Blood Unit for Patients With Hematologic Malignancies

Percent of subjects with cord blood engraftment on or before day 100. Detectable cord blood engraftment should be present by day 100 in at least 50% of patients.

As of 44 days post-transplant, only haploidentical donor chimerism achieved in the one patient enrolled in the Fludarabine, melphalan, and ATG arm. There were no cord cells detected for this patient.

Percent of subjects who are alive 100 days after the stem cell infusion

University of Chicago

Arm I contains fludarabine, melphalan, and antithymocyte globulin (ATG)

Melphalan: Melphalan is given daily for 2 days, overlapping with the completion of fludarabine.

Fludarabine: Fludarabine is given through the vein daily for 5 days.

Antithymocyte Globulin (ATG): ATG is given every other day for 4 days.

Fludarabine, Melphalan, and ATG

Arm II contains fludarabine, busulfan, antithymocyte globulin (ATG), and total body irradiation (TBI).

Fludarabine: Fludarabine is given through the vein daily for 5 days.

Antithymocyte Globulin (ATG): ATG is given every other day for 4 days.

Busulfan: Busulfan is given daily for 4 days.

Total Body Irradiation (TBI): TBI is given twice on the last day.

Fludarabine, Busulfan, ATG, and TBI

Total

<=18 years

Between 18 and 65 years

>=65 years

Female

Male

Gender

Andrew Artz, MD, MS

The only enrolled patient failed to complete the study due to death.

Cord Blood Engraftment by Day 100

Survival at Day 100

Autoimmune Diseases

Bone Marrow Diseases

Precancerous Conditions

Anti-Inflammatory Agents

Prednisone

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

ATG 2.5 mg/kg/day via IV will be given for 4 doses. Each participant will receive only one cycle of therapy. The daily infusion will be administered over at least 6 hours and slowed as necessary to minimize infusion-related symptoms.

All participants will be pre-treated with prednisone (1 mg/kg/day by mouth) 2 days prior to the first ATG does and continuing for 14 days after the final dose to prevent serum sickness

Troy Overfield

Ronald Paquette, MD

Tera Uliano, RN

Alan List, MD

Robin Heggeland, RN

Jaroslaw P. Maciejewski, MD, PhD

Lynn Ruiz

Thomas P. Loughran, Jr., MD

Myelodysplastic syndrome (MDS) is a rare, potentially serious bone marrow disease. Currently available treatments for MDS have been only somewhat beneficial. The purpose of this study is to determine the effects of the medication antithymocyte globulin (ATG) in adults with MDS and to determine which individuals with MDS are most likely to benefit from treatment with ATG.

In people with MDS, the bone marrow stops making healthy blood cells and instead produces poorly functioning, malformed, and immature blood cells. This can lead to anemia resulting from too few healthy red blood cells, infection resulting from too few healthy white blood cells, and bleeding resulting from too few healthy platelets. The exact cause of MDS remains unknown, but it may be caused by abnormal autoimmune activity in which activated T cells, a type of white blood cell, prevent normal bone marrow production. ATG, a medication that inhibits immune function, can restore normal blood production in some people with MDS, but it is not known how this happens and why it does not happen in all MDS patients. The purpose of this study is to examine the effects of ATG in adults with MDS and to determine which individuals with MDS are most likely to benefit from treatment with ATG.

Based on disease severity and likely disease progression, participants will be separated into either a high-risk group or a low-risk group. Participants will be hospitalized for a 4-day period during which they will receive daily infusions of ATG. Oral prednisone will be given 2 days before hospitalization, throughout hospitalization, and then for 14 days after hospitalization to limit the side effects of ATG. Antihistamines and acetaminophen will also be given during hospitalization to reduce the chances of an allergic reaction to ATG. After discharge, all participants will attend monthly study visits that will include blood collection, review of disease symptoms, and evaluation of medication response. At Week 16, participants in the high-risk group will undergo additional blood collection, a bone marrow biopsy, and a thorough evaluation of disease progression and the effects of MDS on daily living abilities. Participants in the low-risk group will undergo these same procedures at Week 24. Follow-up for all participants may last up to 2 years.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Imatinib Mesylate, Busulfan, Fludarabine, and Antithymocyte Globulin for CML Patients	NCT00499889	Leukemia	Imatinib Mesyla... Fludarabine (Fl... Busulfan Antithymocyte G... Tacrolimus Methotrexate Donor lymphocyt... Stem Cell Trans...	- 70 Years	M.D. Anderson Cancer Center
Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation	NCT00720629	Graft Versus Ho...	Visilizumab Tacrolimus Methotrexate Antithymocyte g... Tacrolimus Methotrexate	18 Years - 60 Years	H. Lee Moffitt Cancer Center and Research Institute
Cord Blood Transplantation for Patients With Cancer	NCT01359254	Hematological D...	Melphalan Fludarabine Antithymocyte G... Busulfan Total Body Irra...	18 Years -	University of Chicago
Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation	NCT00720629	Graft Versus Ho...	Visilizumab Tacrolimus Methotrexate Antithymocyte g... Tacrolimus Methotrexate	18 Years - 60 Years	H. Lee Moffitt Cancer Center and Research Institute
Effects of Antithymocyte Globulin in Adults With Myelodysplastic Syndrome	NCT00466843	Myelodysplastic...	Antithymocyte g... Prednisone	18 Years -	Office of Rare Diseases (ORD)
Effects of Antithymocyte Globulin in Adults With Myelodysplastic Syndrome	NCT00466843	Myelodysplastic...	Antithymocyte g... Prednisone	18 Years -	Office of Rare Diseases (ORD)
Cord Blood Transplantation for Patients With Cancer	NCT01359254	Hematological D...	Melphalan Fludarabine Antithymocyte G... Busulfan Total Body Irra...	18 Years -	University of Chicago

Spots Global Cancer Trial Database for antithymocyte globulin (atg)