Stem Cell (Modified Bone Marrow) Transplantation in HIV-Infected Patients With Blood Cancer

NCT00005785 | Completed Phase 1

• 2 other identifiers: 99016799-DK-0167
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the safety and effectiveness of a new stem cell transplant procedure to treat acute or chronic leukemia, multiple myeloma, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphoma in HIV-infected patients. HIV-infected patients usually are not offered bone marrow transplant treatments because they are at increased risk of dying from the intense chemotherapy and radiation therapy used for the procedure. This study uses a modified procedure, transplanting stem cells instead of bone marrow, designed to be less dangerous for such patients. Patients will also undergo a procedure called gene transfer to try to halt progression of their HIV infection. The procedure in this study differs from standard bone marrow transplantation in three ways: Stem cells will be transplanted instead of bone marrow. (Stem cells, which are produced by the bone marrow, mature into the different blood components-white and red cells and platelets.) The stem cell donor will be given a drug that releases these cells from their bone marrow into the blood stream. The cells will then be collected from the donor by apheresis, a procedure in which whole blood is drawn, the stem cells separated and removed, and the rest of the blood returned to the donor.); The procedure will use lower doses of chemotherapy than the conventional method, and will not use radiation therapy; or A laboratory-manufactured gene designed to obstruct HIV reproduction will be inserted into the stem cells, rendering future cells that develop from resistance to the virus. Prospective patients will be tested for matching with an HIV-negative donor (family member) and will undergo a medical history, physical examination and several tests (e.g., breathing tests, X-rays, etc.) to determine eligibility for the study. Study participants will then undergo apheresis to collect white blood cells called lymphocytes. Stem cells will be collected from the donor. Half the donated cells will have the HIV-resistant gene inserted; the other half will have a "control" gene inserted. Additional stem cells collected a second day will not be manipulated. All the donor cells will be frozen until transplantation. Patients will be given drugs (cyclophosphamide, fludarabine and cyclosporin) to prevent the donated cells from being rejected and to prevent them from damaging the patient's organs. The thawed stem cells will then be infused through a vein. 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 once or twice a week for 2 to 3 months with and then will be followed periodically for at least 5 years.

Conditions

Hematologic Neoplasm; HIV Infection

Keywords

Peripheral Blood Stem Cells; Engraftment; Graft vs. Host Disease; Graft-Versus-Leukemia; Donor Apheresis; Cyclophosphamide; Fludarabine; HIV; AIDS; Gene Therapy; Chronic Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia; Chronic Lymphocytic Leukemia

Interventions

GCSF Mobilized Allogeneic PBSC Cultured w/Cytokines; Transduced w/RV DRUG

Eligibility Criteria

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

PATIENTS: Patients with hematologic malignancies curable by allogeneic BMT not currently considered for transplant because of HIV positivity. Chronic myelogenous leukemia (CML): chronic phase. Acute lymphoblastic leukemia (ALL), all patients in complete or partial remission. Acute myelogenous leukemia (AML): AML in first complete or partial remission. (Exceptions: AML with good risk karyotypes: AML M3t, AML M4Eo, AML t. All AML in second or subsequent complete remission.) Myelodysplastic syndromes: refractory anemia (failing ATG and/or CSA) to early transformation to acute leukemia. Chronic myelomonocytic leukemia and myeloproliferative disease. Chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia, in complete or partial remission, Mantle cell lymphoma, relapsed Hodgkin's and non-Hodgkin's lymphoma. Multiple myeloma in remission following chemotherapy. No major organ dysfunction precluding transplantation. DLCO greater than 40 percent predicted. Left ventricular ejection fraction greater than 30 percent. ECOG performance status of 0 to 2. DONOR: HLA identical sibling donor. Fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke, no history of severe heart disease). Informed consent given. DONOR AND PATIENT: Must not be pregnant or lactating. Must be between 18 and 80 years of age. Must not have ECOG performance status of 3 or more. Must not have psychiatric disorder or mental deficiency of the patient or the donor sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible. Must not have a major anticipated illness or organ failure incompatible with survival from BMT as determined by your NIH physician (including encephalopathy, cardiomyopathy, and hepatitis.) Must not have DLCO less than 40 percent predicted. Must not have glomerular filtration rate less than 40. Must not have serum bilirubin greater than 4 mg/dl, transaminases greater than 4x upper limit of normal. Donor must be HIV negative. Donors who are positive for HBV, HCV or HTLV will be used at the discretion of the investigator. Must not have other malignant diseases liable to relapse or progress within 5 years. Donor must be fit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of congestive heart failure or unstable angina, thrombocytopenia).

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

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; HIV Infections; Graft vs Host Disease; Acquired Immunodeficiency Syndrome; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 3, 2000
• First Posted: June 5, 2000
• Study Start: September 1, 1999
• Study Completion: November 1, 2001
• Last Updated: March 4, 2008

Record last verified: 2001-11

Locations

US (1)