Clinical Trials

Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)

Condition(s):

Acute Lymphocytic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Bone Cancer
Bone Tumor
Chronic Lymphocytic Leukemia (CLL)
Chronic Myelogenous Leukemia (CML)
Leukemia
Lymphoma
Myelodysplastic Syndrome
Cancer
Blood Diseases and Disorders
Bone Marrow Transplant
Bone Tumor (Bone Neoplasms)
Hematologic Cancer
Hematology
Lymphocytic Leukemia, Chronic
Neoplasms
Stem Cell Transplant
T-Cell Lymphoma
Blood Disorder
Myelodysplastic Syndromes

Purpose: This study will try to improve the safety and effectiveness of stem cell transplant procedures in patients with cancers of the blood. It will use a special machine to separate immune cells (T cells) from the blood of both the donor and the patient and will use photodepletion, a laboratory procedure that selectively kills cancer cells exposed to light. These special procedures may reduce the risk of graft-versus-host-disease (GVHD), a serious complication of stem cell transplants in which the donor's immune cells destroy the patient's healthy tissues, and at the same time may permit a greater graft-versus-leukemia effect, in which the donated cells fight any residual tumor cells that might remain in the body. Patients between 18 and 75 years of age with a life-threatening disease of the bone marrow (acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome) may be eligible for this study. Candidates must have a family member who is a suitable tissue match. Participants have a central intravenous (IV) line placed into a large vein. The tube is used for giving the donated stem cells and antibiotics and other medicines, for transfusions of red blood cells and platelets, and for collecting blood samples. Treatment starts with a conditioning regimen of chemotherapy (fludarabine and cyclophosphamide) and total body irradiation to suppress immunity and prevent rejection of the donated stem cells. The day after chemotherapy ends, the stem cells are given through the central line. This is followed by transfusion of the donor's immune cells, which have been treated to remove cells that could cause severe GVHD. Also to minimize the risk of GVHD, patients are given cyclosporine. Not all participants receive the same amount of this drug; in order to determine how much immunosuppression is needed to protect against severe GVHD, the length of treatment with cyclosporine varies among patients, depending on when they entered the study and how well preceding patients did. The average hospital stay for stem cell transplantation is 3 to 4 weeks. Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation. The patient's referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter. Patient follow-up visits are scheduled at NIH at 1, 2, and 3 years after transplantation. After 3 years, participants are offered the opportunity to enroll in NHLBI's long-term evaluation and follow-up care protocol.

Eligibility:

Minimum Age:

18 Years

Maximum Age:

75 Years

Accepts Healthy Volunteers:

No

- INCLUSION CRITERIA:

Recipient Criteria:

Diagnosed with one of the following hematological conditions:

- Chronic myelogenous leukemia (CML): chronic phase who have failed treatment with
imatinib, have intolerance to imatinib, or who did not receive imatinib at
therapeutic doses within the first 12 months from diagnosis; accelerated phase or
blast transformation.

- Acute B-lymphoblastic leukemia (B-ALL): any of these categories: B-ALL in first
remission with high-risk features (presenting leukocyte count greater than 100,000/cu
mm, Karyotypes t9; 22, t4, t19, t11, biphenotypic leukemia), all second or subsequent
remissions, primary induction failure, partially responding or untreated relapse.

- Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk
karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8; 21). All AML in second or
subsequent remission, primary induction failure and resistant relapse.

- Myelodysplastic syndromes (MDS): any of these categories - refractory anemia with
transfusion dependence, refractory anemia with excess of blasts, transformation to
acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative
syndromes.

- Myeloproliferative disorders including atypical (Ph negative) chronic myeloid and
neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential
thrombocythemia in transformation to acute leukemia or with progressive transfusion
requirements or pancytopenia.

- Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky
progressive disease or with thrombocytopenia (less than or equal to 100,000 /microl)
or anemia (less than or equal to 10g/dl) not due to recent chemotherapy.

- Non-Hodgkin's lymphoma including Mantle cell lymphoma relapsing or refractory to
standard of care treatments.

- Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed following
standard of care treatments.

- Ages 18-75 years inclusive.

- HLA identical (6/6) related donor.

- Ability to comprehend the investigational nature of the study and provide informed
consent.

Donor Criteria:

- Related HLA identical (6/6) with recipient.

- Weight greater than or equal to 18 kg.

- Age greater than or equal to 2 or less than or equal to 80 years old.

- For adults: Ability to comprehend the investigational nature of the study and provide
informed consent. For minors: Written informed consent from one parent or guardian
and informed assent: The process will be explained to the minor on a level of
complexity appropriate for their age and ability to comprehend.

EXCLUSION CRITERIA:

Recipient Criteria (any of the following):

- Malignant cells expressing a T cell phenotype (in particular T-ALL and T cell NHL).

- DLCO less than 65 percent predicted.

- Left ventricular ejection fraction less than 40 percent (evaluated by ECHO) or less
than 30 percent (evaluated by MUGA).

- AST/SGOT greater than 20 times ULN (CTCAE grade IV v3.0).

- Bilirubin greater than 10 times ULN (CTCAE grade IV v3.0).

- Creatinine greater than 6 times ULN (CTCAE grade IV v 3.0).

- HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or
human T-cell lymphotropic virus (HTLV-1/II) are not excluded from participation).

- Positive pregnancy test for women of childbearing age.

- Prior allogeneic stem cell transplantation.

- Estimated probability of surviving less than three months.

- Major anticipated illness or organ failure incompatible with survival from
transplant.

- Severe psychiatric illness or mental deficiency sufficiently severe as to make
compliance with the transplant treatment unlikely and informed consent impossible.

Donor Criteria (any of the following):

- Pregnant or lactating.

- Unfit to receive filgrastim (G-CSF) and undergo apheresis (abnormal blood counts,
history of stroke, uncontrolled hypertension).

- Sickling hemoglobinopathies including HbSS, HbAS, HbSC.

- HIV positive Donors who are positive for hepatitis B (HBV), hepatitis C (HCV) or
human T-cell lymphotropic virus (HTLV-I/II) will be used at the discretion of the
investigator following counseling and approval from the recipient.

- Severe psychiatric illness or mental deficiency sufficiently severe as to make
compliance with the donation of stem cells unlikely and informed consent impossible.

Other Location(s): Bethesda, Maryland United States

Terms: This is an abstract courtesy of ClinicalTrials.gov, a service of the US National Institute of Health Developed by the National Library of Medicine. ClinicalTrials.gov provides regularly updates information about federally and privately supported clinical research in human volunteers.