Modified Bone Marrow Stem Cell Transplantation for Chronic Myelogenous Leukemia

NCT00001144 | Completed Phase 2

• 2 other identifiers: 00000100-H-0001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the safety and effectiveness of a new stem cell transplant procedure for treating chronic myelogenous leukemia (CML). Transplantation of donated stem cells (cells produced by the bone marrow that mature into the different blood components-white cells, red cells and platelets) is a very effective treatment for CML. However, despite its success in a large number of patients, there is still a significant risk of death from the procedure. In addition, it results in sterility and leaves patients at increased risk for other cancers and for eye cataracts. These complications result from the intensive chemotherapy and radiation patients receive before the transplant to rid the body of cancer cells. In this study, radiation will not be used and chemotherapy drugs will be given in lower doses to try to reduce the dangers of the procedure. Patients with CML will be tested for matching with a donor (family member) and will undergo a medical history, physical examination and several tests (e.g., breathing tests, X-rays, and others) to determine eligibility for the study. Participants will then undergo apheresis to collect lymphocytes (white blood cells important in the immune system). In apheresis, whole blood is drawn through a needle in the arm, similar to donating a unit of blood. The required component-in this case, lymphocytes-are separated and removed, and the rest of the blood is returned through a needle in the other arm. Each day starting five days before the transplant, the donor will be given an injection of G-CSF, a drug that releases stem cells from the bone marrow into the blood stream. The cells will be collected after the fifth injection and again after a sixth injection the following day. Meanwhile, patients will be given cyclophosphamide and fludarabine, and perhaps anti-thymocyte globulin, to prevent rejection of the donated cells. On the day of the transplant, patients will be given cyclosporin to prevent graft-versus-host-disease, a disease in which the donor cells react against the patient's cells. They may also be given lymphocytes after the transplant to boost the immune system and destroy leukemia cells. After 30, 60 and 100 days, bone marrow cells and circulating lymphocytes will be checked to see how many are of donor cell origin. If less than 100 percent are of donor origin, more lymphocytes will be transfused. Patients will have physical examinations and blood tests at least weekly for 3 months and then periodically for 5 years.

Conditions

Chronic Myeloid Leukemia; Graft vs Host Disease

Keywords

Peripheral Blood Stem Cells; Engraftment; Graft vs. Host Disease; Graft-Versus-Leukemia; Graft-Versus-Tumor/Melanoma; Chronic Myelogenous Leukemia

Interventions

Modified bone marrow stem cell transplantation DRUG

Eligibility Criteria

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

PATIENTS: Patients in chronic phase CML. Age 10 to 50. Informed consent given. Availability of HLA identical or single HLA-locus mismatched family donor. Females must not be pregnant or lactating. Must not have ECOG performance status of 3 or more. Must not have a psychiatric disorder or mental deficiency severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible. Must not have major anticipated illness or organ failure incompatible with survival from PBSC transplant. Must not have diffusion capacity of carbon monoxide (DLCO) less than 40% predicted. Must not have left ventricular ejection fraction: less than 30%. Must not have serum creatinine greater than 50% above normal as defined by age. Must not have serum bilirubin greater than 4 mg/dl. Must not have transaminases greater 5 x upper limit of normal. Must not have other malignant diseases liable to relapse or progress within 5 years. DONOR: HLA identical or single HLA-locus mismatched family donor, up to 80 years old. Informed consent given. Females must not be pregnant or lactating. Donor must be fit to receive G-CSF and undergo apheresis. (No controlled hypertension, no history of congestive heart failure or unstable angina, thrombocytopenia). Must be HIV negative. Donors who are positive for hepatitis B (HBV), hepatitis C (HBC) or human T-cell lymphotropic virus (HTLV)-I will be used at the discretion of the investigator.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ringden O, Remberger M, Ruutu T, Nikoskelainen J, Volin L, Vindelov L, Parkkali T, Lenhoff S, Sallerfors B, Mellander L, Ljungman P, Jacobsen N. Increased risk of chronic graft-versus-host disease, obstructive bronchiolitis, and alopecia with busulfan versus total body irradiation: long-term results of a randomized trial in allogeneic marrow recipients with leukemia. Nordic Bone Marrow Transplantation Group. Blood. 1999 Apr 1;93(7):2196-201.

  PMID: 10090927 BACKGROUND

• Stucki A, Leisenring W, Sandmaier BM, Sanders J, Anasetti C, Storb R. Decreased rejection and improved survival of first and second marrow transplants for severe aplastic anemia (a 26-year retrospective analysis). Blood. 1998 Oct 15;92(8):2742-9.

  PMID: 9763558 BACKGROUND

• Armitage JO. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827-38. doi: 10.1056/NEJM199403243301206. No abstract available.

  PMID: 8114836 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Graft vs Host Disease; Melanoma

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: October 1, 1999
• Study Completion: October 1, 2002
• Last Updated: October 7, 2008

Record last verified: 2002-10

Locations

US (1)