Total-Body Irradiation, Fludarabine, and Alemtuzumab Followed By Stem Cell Transplant in Treating Patients With Myeloproliferative Disorder, MS, AML, or CML

NCT00069992 | Terminated Phase 2 DMC

• 1 other identifier: H-10857-MPDMDSBMT
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

Patients are being asked to participate in this study because they have a malignant blood disease such as Myelodysplastic Syndrome (MDS), Myeloproliferative Disorder (MPD), Acute Myelogenous Leukemia (AML) or Chronic Myelogenous Leukemia (CML). We feel that patients could benefit from an allogeneic (meaning the cells come from a donor other than themself) stem cell transplant. The donor would be a family member or an unrelated person that is felt to be a good match for the patient. Stem cells are cells that are made in the bone marrow (spongy material that fills the middle of the bones). As the stem cells grow, they change into different types of blood cells that they need. This includes red blood cells that carry oxygen around the body, white blood cells that help to fight infections, and platelets that help to prevent and stop bleeding. Usually, patients are given high doses of chemotherapy before a stem cell transplant. High doses of chemo destroy the bone marrow. Healthy stem cells from a donor are then given to replace the patient's unhealthy cells. However, because of complications with the patient's disease, they have a high risk of having life-threatening side effects. These include serious damage to organs such as the lung, liver, kidney and heart. There is also an increased risk of bacterial, fungal, and viral infections. The other major problem is when a donor's stem cells (also called the graft) find that the patient's cells ( the host cells) are not the same. The donor cells may try to destroy the host's cells. The cells at high risk are those of the skin, liver and intestines. This is called graft versus host disease (GVHD) and it can be fatal. Recently, doctors have been able to use less toxic chemotherapy treatments before patients receive their transplants. This less toxic treatment helps reduce some of the treatment related problems mentioned above. Patient's are being asked to be involved in a research study that uses this approach. One major risk of this low dose treatment is that the patient's body may reject the donor cells. This is called graft rejection. This study is designed to see if this low dose treatment is safe and effective. This treatment plan adds CAMPATH 1H (a special protein called an antibody) to a low dose chemotherapy regimen. After chemo, the patient will receive an allogeneic (cells come from a donor) stem cell transplant. Adding CAMPATH 1H to the transplant medicines may help in treating the disease. CAMPATH 1H may reduce life-threatening and treatment related side effects like GVHD. CAMPATH 1H stays active in the body for a long time which means it may work longer to prevent GVHD. CAMPATH 1H destroys lymphocytes, a type of white cells that help fight infection, and this helps prevent graft rejection. We want to see if the addition of CAMPATH 1H to the patient's pre-transplant low dose chemotherapy will decrease the side effects from an allogeneic stem cell transplant, while providing a curative treatment for patients with blood disorders.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Myelodysplastic Syndromes

Keywords

polycythemia vera; essential thrombocythemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; primary myelofibrosis; chronic myelogenous leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (2)

• Day 100 Non-relapse mortality,

  Safety and feasibility of submyeloablative conditioning as a preparative regimen for blood stem cell transplantation

  100 days

• Day 100 graft rejection

  Safety and feasibility of submyeloablative conditioning as a preparative regimen for blood stem cell transplantation

  100 days

Secondary Outcomes (2)

• 1 year disease free survival

  1 year

• Complete Remission at 100 days

  100 days

Study Arms (1)

Submyeloablative Allogeneic Stem Cell Transplant

EXPERIMENTAL

Total Body Irradiation Fludarabine Campath 1H

Radiation: Total Body Irradiation; Drug: Fludarabine; Drug: Campath 1H

Interventions

Total Body Irradiation RADIATION

Total body irradiation of 450cGy as a single dose, day -6

Also known as: TBI

Submyeloablative Allogeneic Stem Cell Transplant

Fludarabine DRUG

Fludarabine 30mg/m2 Day -5 to -2

Also known as: Fludara

Submyeloablative Allogeneic Stem Cell Transplant

Campath 1H DRUG

Campath 1H dosing as per institutional SOPs Day -5 to -2

Also known as: Alemtuzumab

Submyeloablative Allogeneic 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:

• Myelodysplastic syndrome with IPSS score \> 0.(Appendix B) Or
• Myeloproliferative disorders
• Primary Myelofibrosis with Lile score of 1 or 2 (Appendix C)
• Polycythemia Vera or Essential Thrombocythemia transformed to AML or Myelofibrosis and PV "spent phase" or
• Acute myelogenous leukemia or
• Chronic myelogenous leukemia
• Available Healthy Donor without any contraindications for donation. 5/6 or 6/6 related donor or 5/6 or 6/6 unrelated donor (molecular typing for DRB1)
• Able to give informed consent

You may not qualify if:

• Patient is pregnant or lactating or unwilling to use contraceptives.
• HIV positive patient
• Uncontrolled intercurrent infection
• Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater)
• Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater)
• Hemodialysis dependent.
• Active hepatitis or cirrhosis with total bilirubin, SGOT, and SGPT greater than 3 x normal.
• Concurrent solid organ malignancy not in remission, except for Stage 0 or A prostate cancer.
• Unstable cerebral vascular disease or recent hemorrhagic stroke (less than 6 months)
• Active CNS disease from hematological disorder.

Sponsors & Collaborators

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

Study Sites (2)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Leukemia; Myelodysplastic Syndromes; Polycythemia Vera; Thrombocythemia, Essential; Primary Myelofibrosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Congenital Abnormalities

Interventions

Whole-Body Irradiation; fludarabine; fludarabine phosphate; Alemtuzumab

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• George Carrum, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor; Director-Adult Outpatient Clinic

Study Record Dates

• First Submitted: October 3, 2003
• First Posted: October 7, 2003
• Study Start: December 1, 2001
• Primary Completion: September 1, 2006
• Study Completion: April 1, 2007
• Last Updated: October 10, 2012

Record last verified: 2012-10

Locations

US (2)