Blood & Marrow Transplantation

Research Activities

Laboratory and Translational Research

CHNY-01-501 (IRB#: AAAA5185) A Pilot Study of Sequential Myeloablative Stem Cell Transplantation and Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation Followed by Adoptive Cellular Immunotherapy in Patients with Refractory or Recurrent Non-Hodgkin’s Lymphoma and Hodgkin's Disease
PI: Brigid Bradley, MD Co-PI: Mitchell Cairo, MD
Children and adults less than 55 years of age with non-Hodgkin’s lymphoma or Hodgkin’s disease with recurrent or refractory disease are eligible. The treatment plan includes high dose chemotherapy followed by autologous stem cell transplantation. Local radiation therapy to tumor areas will follow in selected patients. Some patients will also receive antibody therapy. All patients will go on to receive reduced intensity conditioning chemotherapy and immune therapy, followed by an infusion of donor stem cells (allogeneic stem cell transplant). Patients will receive stem cells from a matched family donor or a matched unrelated donor (cord blood, peripheral blood, or bone marrow) based on the best available match. Patients with a matched family or unrelated adult donor will be eligible to receive donor lymphocyte infusions (immune cells or DLI) if they have evidence of persistent disease following the allogeneic stem cell transplant.

CHNY-01-515 (IRB#: AAAA2533) A Phase I Dose Escalation of Gemtuzumab Ozogamicin in Combination with Busulfan and Cyclophosphamide (Bu/Cy) (Immunochemotherapy) and Allogeneic Stem Cell Transplantation (AlloSCT) in Patients with High Risk CD33+ Acute Myelogenous Leukemia/Myelodysplastic Syndrome/Juvenile Myelomonocytic Leukemia (AML/MDS/JMML)
PI: M. Cairo, MD
Patients less than 65 years of age with AML in induction failure, AML in 1st, 2nd, or 3rd relapse, AML greater than 3rd CR, MDS with greater than 6% bone marrow blasts at diagnosis or JMML with 6% bone marrow myeloblasts at diagnosis with adequate organ function, without active CNS disease, female patients that are not pregnant and meeting performance status criteria are eligible. No restriction to gender or race. Patients will receive a myeloablative busulfan/cyclophosphamide/thymoglobulin (Bu/Cy) conditioning regimen preceded by lovenox and gemtuzumab (GO) and followed by AlloSCT. The first group of 3 patients will receive gemtuzumab IV starting 14 days prior to AlloSCT at dose level 1 (3.0 mg/m2). If no serious side effects occur, the assigned dose will be increased by 1.5 mg/m2 for subsequent groups of patients, until the maximum tolerated dose has been determined. Four dose levels are planned. GO dose escalation will occur in groups of 3, age stratified (<21 years/>21 yrs). Doses will not be increased for individual patients. Lovenox will be started 1 day prior to GO to help reduce the liver side effects associated with GO. Busulfan (with lorazepam seizure prophylaxis) will be given Day -7 through Day -4 and cyclophosphamide Day -3 and Day -2. This is followed by a day of rest, then a bone marrow (BM) or cord blood infusion from a related family or unrelated matched donor (AlloSCT).

CHNY-01-519 (IRB#: AAAB3096) National Marrow Donor Program (NMDP) and Center for International Blood and Marrow Transplant Research (CIBMTR) Protocol for a Research Database for Hematopoietic Stem Cell Transplantation and Marrow Toxic Injuries
PI: M. Cairo, MD
All donors and recipients participating in the research database will give informed consent to have their data included in the NMDP and CIBMTR database. The primary goal of the CIBMTR Research Program is to improve the safety and effectiveness of (HSC) hematopoietic stem cell transplantation for both donors and recipients. The NMDP database was established in 1989 and the ICMTR database was established in 1972. The Research Database contains demographic and clinical data on allogeneic related and unrelated donors and their donation experiences. The data contained in the research databases are observational data. CIBMTR does not determine which therapies are used for patients, but rather collects information regarding g therapies as they are applied by transplant centers. A secondary goal of the CIBMTR Research Program is to improve treatments and outcomes for those individuals who have been exposed to radiation or other chemicals that are toxic to marrow.

CHNY-01-520 (IRB#: AAAB3097) National Marrow Donor Program (NMDP) Protocol for a Research Sample Repository for Allogeneic Hematopoietic Stem Cell Transplantation
PI: M. Cairo, MD
In 1987, the NMDP established the NMDP Research Sample Repository. The primary objective of this repository is to make blood samples available for research studies related to histocompatibility and HSC transplantation. Blood samples are donated by donors, CBUs and recipients who have registered, donated or received an allogeneic HSC transplant covered under the C.W. Bill Young Transplantation Program. The following are types of studies that the NMDP allows the samples to be used for without obtaining additional consent from the recipient. Studies to: • Improve the understanding of tissue matching for HSC donors and recipients; • Determine and evaluate the factors that affect transplant outcome; • Study the distribution of HLA tissue types in different populations; e.g., study tissue typing differences between different racial and ethnic populations to help develop methods to improve tissue matching between donors and recipients, including testing of rare HLA types. • Use for delinked (anonymous) research. Donors are eligible to participate in the NMDP Research Sample Repository if they have donated or are scheduled to donate HSCs to an allogeneic recipient either by a marrow harvest or by apheresis.

CHNY-02-516 (IRB#: AAAB3095) Unrelated Donor Stem Cell Transplantation (UD AlloSCT) for Patients with Malignant and Non-Malignant Disorders
PI: M. Cairo, MD, Co-PI: D. George, MD
This is a non-randomized study to test the safety and response of unrelated matched donor allogeneic stem cell transplantation (UDAlloSCT) with either myleoablative (full intensity) or reduced intensity conditioning therapy in patients with selected malignant and non-malignant disorders. UDAlloSCT has been performed in both adults and children as an alternative transplant for patients who lack a HLA-matched family donor in both malignant and non-malignant disease. Selected patients equal to or less than 55 years meeting the malignant and non-malignant eligibility criteria for disease status, signed inform consent, adequate performance status, and organ function requirements with the following malignant diseases: chronic myeloid leukemia (CML), acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), juvenile chronic myeloid leukemia (JCML), acute lymphoblastic leukemia (ALL) and lymphomas; or the following non-malignant diseases: bone marrow failure syndromes, immunodeficiencies, inborn errors of metabolism, and histiocytosis, will be considered for enrollment.

Patients will receive one of four treatment regimens: Full intensity conditioning consisting of rabbit antityhymocyte globulin and thiotepa and cyclophosphamide with total body irradiation (TBI) followed by UDAlloSCT; Full intensity conditioning consisting of busulfan, melphalan and rabbit antithymocyte globulin without TBI followed by UDAlloSCT; Reduced intensity conditioning consisting of busulfan, fludarabine and alemtuzumab followed by UDAlloSCT; (In patients with a prior history of hepatic toxicity and/or high-risk for VOD or other liver toxicity, the busulfan in this regimen can be substituted with melphalan); or Patients diagnosed with Fanconi's anemia will receive TBI for 1 day and conditioning chemotherapy consisting of fludarabine, cyclophosphamide and anti-thymocyte globulin followed by UDAlloSCT.

CHNY-05-525 (IRB#: AAAB2879) CD34+ Stem Cell Selection for Patients Receiving Partially Matched Family or Matched Unrelated Adult Donor Allogeneic Stem Cell Transplantations for Malignant and Non-Malignant Disease
PI: M. Cairo, MD, Co-PI: J. Schwartz, MD
The primary aim of this study is to determine if CD34+ stem cell selection in children, adolescents and young adults receiving partially matched family donor or matched unrelated adult donor allogeneic bone marrow or peripheral blood stem cell transplant is safe and well tolerated and associated with a low incidence of serious (Grade III/IV) acute and chronic GVHD. Patients less than 26 years of age with selected malignant or non-malignant diseases (malignant: chronic myeloid leukemia (CML), acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), juvenile chronic myeloid leukemia (JCML), acute lymphoblastic leukemia (ALL) and lymphomas; or the following non-malignant diseases: bone marrow failure syndromes, immunodeficiencies, inborn errors of metabolism, and histiocytosis) and an 8/10, 9/10 or 10/10 matched unrelated adult donor or a 3/6,4/6, or 5/6 matched family donor will be eligible. CD34+ cells will be selected from either donor bone marrow or peripheral blood stem cells. Depending on diagnosis, patients will receive one of four treatment regimens: Full intensity conditioning consisting of rabbit antityhymocyte globulin and thiotepa and cyclophosphamide with total body irradiation (TBI); Full intensity conditioning consisting of busulfan, melphalan and rabbit antithymocyte globulin without TBI; Reduced intensity conditioning consisting of busulfan, fludarabine and alemtuzumab; or Patients diagnosed with Fanconi's anemia will receive TBI for 1 day and conditioning chemotherapy consisting of fludarabine, cyclophosphamide and anti-thymocyte globulin followed by allogeneic stem cell transplantation with unrelated adult CD34 selected donor stem cells.

CHNY-06-532 (IRB#: AAAC0918) Clofarabine in Combination with Cytarabine and Total Body Irradiation Followed by Allogeneic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia and Acute Non-Lymphoblastic Leukemia
PI: M. Cairo, MD
Patients equal to or less than 30 year of age with acute lymphoblastic leukemia or acute non-lymphoblastic leukemia in CR3 having received a minimum of one round of reinduction chemotherapy and one round of consolidation chemotherapy after second relapse and meeting additional eligibility criteria are eligible to be enrolled. This is a two part study (A and B) to determine the maximum tolerated dose (MTD) and/or safe dose of clofarabine given in combination with ARA-C and total body irradiation (TBI) and followed by allogeneic stem cell transplantation (AlloSCT) (Part A) and to test the safety and efficacy of this regimen utilizing the established MTD and/or safe dose of clofarabine from Part A (Part B). At study entry during Part A, a clofarabine dose level will be assigned to each patient. During Part B, the most effective or safe/tolerated dose of clofarabine will be used.

CHNY-07-534 (IRB#: AAAC7574) A Single arm Study to Assess the Safety of Transplantation with Umbilical Cord Blood Augmented With Human Placental-Derived Stem Cells From Partially- or fully-HLA Matched Related Donors in Subjects with Certain Malignant Hematologic Diseases and Non-malignant Disorders
PI: M. Cairo, MD
This study will assess the safety of transplantation with partially or fully HLA-matched, related-donor umbilical cord blood (UCB) stem cells augmented with human placental-derived stem cells (HPDSC) from the same donor in subjects with malignant or non-malignant disorders requiring a stem cell transplant. Eligible diagnoses are: high-risk myelodysplastic syndrome (MDS), high-risk acute myelogenous leukemia (AML), high-risk acute lymphocytic leukemia (ALL), sickle cell anemia with significant disease manifestations, beta (ß ) thalassemia major (S ß thalassemia) with significant disease manifestations, selected inborn errors of metabolism, selected bone marrow failure syndromes, or selected severe combined immunodeficiency disease (SCID). All eligible subjects less than or equal to 21 years of age will undergo either full myeloablation, reduced intensity pre-transplant conditioning, or non-myeloablative-pre-transplant conditioning (as dictated by the disorder for which the transplant is indicated) followed by transplantation with UCB and infusion of HPDSC. Standard of care GvHD prophylaxis will also be administered. Subjects will be evaluated at baseline, during the pre-transplant conditioning period, at the time of transplant, and for at least two years post-transplant.

CHNY-07-535 (IRB#: AAAD2389) GC P#02.01.001 A Multi-Center, Multi-National, Historical Cohort Controlled Study to Evaluate Efficacy and Safety of Transplantation of StemEx, Umbilical Cord Blood Stem and Progenitor Cells Expanded Ex Vivo, in Subjects with Hematologic Malignancies following Myeloablative Therapy
PI: M. Bhatia, MD, Co-PI: D. George
Subjects age greater than or equal to 12 and less than or equal to 55 with high-risk hematologic malignancies who are candidates for allogeneic stem cell transplantation (SCT) including acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL), at second or later remission, or in first remission with high-risk cytogenetics or other high-risk criteria, or relapse, or subjects with chronic myeloid leukemia (CML) in first chronic phase refractory to Gleevec, or in second or subsequent chronic phase or accelerated phase or subjects with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) with chemosensitive disease and with induction failure or relapse, or subjects with myelodysplastic syndrome (MDS) with intermediate 2 or high-risk International Prognostic Scoring System (IPSS) score. StemEx® is a stem/progenitor cell-based product of ex vivo expanded allogeneic umbilical cord blood (UCB), which is administered to the subject in combination with the unmanipulated portion of the same cord blood unit (CBU). The unmanipulated CBU portion is transplanted on day 0. StemEx® is derived from the smaller (or equal) CBU portion which is expanded ex vivo for 21 days in the presence of cytokines and tetraethylenepentamine (TEPA) and is transplanted on day 1.

CHNY-08-536 (IRB#: AAAD5420) A Pilot Study of Reduced Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (ALLOSCT) in Children with Recessive Dystrophic Epidermolysis Bullosa (RDEB)
PI: M. Cairo, MD
Patients with recessive dystrophic epidermolysis (RDEB) ages =21 years of age will receive reduced intensity conditioning over 7 days with busulfan (standard dose)/fludarabine/alemtuzumab followed by an allogeneic stem cell infusion from a healthy related bone marrow or cord blood donor or an unrelated cord blood donor. Stringent supportive care measures will be implemented. Blood and skin samples are obtained to measure outcomes at specific time intervals.

CHNY-09-538 (IRB# AAAD8457) NCH 08-00234: A Multicenter Pilot Study of Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation with In-Vivo T-Cell Depletion to Evaluate the Role of NK cells and KIR Mis-Matches in Relapsed or Refractory High-Risk Neuroblastoma
Site PI: P. Satwani, MD
Patients ages 1-18 year of age with a diagnosis of neuroblastoma who after completion of induction have no response, mixed response, or progressive disease or patients who have relapsed following high-dose chemoradiotherapy including autologus stem cell transplantation and meeting additional organ function and exclusion criteria are eligible. Conditioning chemotherapy consisting of busulfan/fludarabine/ATG will be given followed by allogeneic stem cell transplantation from a matched related or unrelated bone marrow or peripheral blood stem cell donor. Blood tests for biology studies (NK cell function and KIR receptors) will be evaluated at specific timepoints throughout the study.

CHNY-09-141 (IRB# AAAE7732) 6115A1-3003-WW: A Phase 3, Open-label Trial to Evaluate the Safety, Tolerability, and Immunogenicity of 13-valent Pneumococcal Conjugate Vaccine Followed by 23-valent Pneumococcal Polysaccharide Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant Aged 2 Years and Older
Site PI: M. Cairo, MD
This is a study to evaluate a pneumococcal vaccine in patients 2 years of age or older who have had an allogeneic stem cell transplant (AlloSCT) for a hematological malignancy approximately 3-6 months before study entry. After an AlloSCT the immune system is similar to that of a baby’s and has to be stimulated with the help of vaccines to produce antibodies to fight off germs. People who have had an AlloSCT are more likely than others to get ill from a germ called Streptococcus pneumoniae (pneumo germ). There are many different types of pneumo germs. Vaccines can help to fight off germs. Most people who have had a stem cell transplant are offered a vaccine called 23vPS vaccine to help protect against common pneumo germs. It is usual to wait about one year because if the 23vPS vaccine is given any sooner it does not work very well. We are doing this research study to see if this test vaccine, called 13vPnC vaccine, can be given sooner than one year to help protect against pneumo germs earlier. 13vPnC vaccine is similar to a vaccine that is given to healthy babies around the world, and which is known to protect against common pneumo germs. In this study we will give subjects injections of 13vPnC vaccine and an injection of 23vPS vaccine. These will be given over 9 months. Blood samples will be taken to measure how many antibodies a patient makes after each injection of each vaccine.