Methods to Enhance the Safety and Effectiveness of Stem Cell Transplants

• Status: Completed
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Bone marrow stem cell transplants (otherwise called bone marrow transplants) from healthy donors are sometimes the only means of curing hematological malignant diseases such as acute and chronic leukemias, myelodysplastic syndrome, myeloproliferative diseases and lymphomas. Before transplant the patient receives chemotherapy and radiation treatment to reduce the malignancy to low levels and to prevent rejection of the transplant. The transplant restores the blood counts to normal and replaces the patients immunity with that of the donor. The donors immune cells increase the effect of the transplant by attacking remaining malignant cells. Donor immune cells (especially those called T lymphocytes) also attack healthy non-cancerous cells and tissues of the recipient causing "graft-versus-host-disease" (GVHD). Strong GVHD reactions occurring within weeks after the transplant can be life-threatening . In this study we remove most of the T lymphocytes from the transplant to minimize the risk of GVHD. However to improve immunity against residual malignant cells and boost immunity to infections, donor T cells (stored frozen at time of transplant) are given back around 90 days after the transplant when they have a reduced risk of causing serious GVHD.

Any patient between 10 and 75 years of age with acute or chronic leukemia, myelodysplastic syndrome, myeloproliferative syndromes or lymphoma, who have a family member who is a suitable stem cell donor may be eligible for this study. Candidates are screened with a medical history and various tests and examinations.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Cyclophosphamide; Cyclosporine; Cyclosporins; Fludarabine; Fludarabine phosphate

Criteria

INCLUSION CRITERIA - RECIPIENT:

• Ages 10-75 years inclusive

• Chronic myelogenous leukemia (CML):

• Subjects under the age of 21 in chronic phase

• Subjects ages 10-75 in 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.

• Subjects ages 10-75 in accelerated phase or blast transformation.

• Acute lymphoblastic leukemia (ALL): any of these categories: 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-Hodgkins lymphoma including Mantle cell lymphoma relapsing or refractory to standard of care treatments

• Multiple myeloma, Waldenstrom's macroglobulinemia, unresponsive or relapsed following standard of care treatments.

• HLA identical (6/6) related donor

• 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. Informed oral consent from minors: the process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.

EXCLUSION CRITERIA - RECIPIENT:

• Estimated probability of surviving less than three months

• Major anticipated illness or organ failure incompatible with survival from transplant

• Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and making informed consent impossible.

• Positive pregnancy test for women of childbearing age.

• HIV positive

• Diffusion Capacity of Lung for Carbon Monoxide (DLCO) adjusted for ventilation and hemoglobin less than 65 percent predicted

• Left ventricular ejection fraction less than 40 percent

• Aspartate Aminotransferase (AST)/Serum Glutamate Oxaloacetate Transaminase (SGOT) greater than 10 times upper limit of normal (ULN) (CTCAE grade IV v3.0)

• Bilirubin greater than 5 times upper limit of normal (ULN) (CTCAE grade IV v3.0)

• Creatinine greater than 4.5 times upper limit of normal (ULN) (CTCAE grade IV v 3.0)

• Prior allogeneic stem cell transplantation.

INCLUSION CRITERIA - DONOR:

• Related donor, 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 - DONOR:

• Pregnant. Lactating donors permitted provide breast milk is discarded during the days that G-CSF is given

• 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. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible