Study of Parathyroid Hormone Following Sequential Cord Blood Transplantation From an Unrelated Donor
Study of Parathyroid Hormone Following Sequential Cord Blood Transplantation From an Unrelated Donor
The purpose of this study is to determine whether the addition of parathyroid hormone after a
 sequential cord blood transplant will improve engraftment, which is the ability of the
 transplanted stem cells to grow and to successfully begin producing new blood cells.
In this phase II, single stage study, participants will include 40 adults who are candidates
 for a hematopoietic stem cell transplant. All participants will undergo a sequential cord
 blood transplant using a well-known myeloablative regimen of fludarabine, cyclophosphamide,
 and total body irradiation, which is appropriate for those individuals who are likely to
 benefit from an ablative regimen. Tacrolimus will be combined with mycophenolate mofetil
 (MMF) for the graft-versus-host disease (GVHD) prophylaxis regimen. Parathyroid hormone (PTH)
 will be added to this regimen in an attempt to improve engraftment. PTH is an approved drug
 with minimal side effects in individuals with osteoporosis; the dose of PTH has been
 determined from a phase I study in individuals with hematologic cancer.
Inclusion Criteria:

 -  One of the following diagnoses:

 1. Chronic myelogenous leukemia (CML) accelerated phase or second stable phase;
 individuals in the first chronic phase are eligible if they have resistance to
 imatinib

 2. Myelodysplasia

 3. Aplastic anemia that is not responding to immunosuppressive therapy

 4. Myelofibrosis, either primary or secondary to polycythemia vera

 5. Relapsed lymphoma or Hodgkin's disease

 6. Stage III/IV chronic lymphocytic leukemia (CLL), relapsed after or refractory to
 at least one fludarabine containing regimen

 7. Acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) in
 complete remission (CR) 2 or greater, or CR 1 with high risk features

 -  No prior autologous stem cell transplant

 -  Eastern Cooperative Oncology Group (ECOG) performance status of less than 2

 -  Lack of 6/6 or 5/6 matched related donor OR lack of 10/10 matched unrelated donor OR
 no available donor in the appropriate time frame to perform a potentially curative
 stem cell transplant

 -  Diffusing capacity of the lung for carbon monoxide (DLCO) greater than 50% of
 predicted value

 -  Left ventricular ejection fraction (LVEF) greater than 50% of predicted value

 -  Calcium levels less than 10.5 mg/dl

 -  Phosphate levels greater than 1.6 mg/dl

 Exclusion Criteria:

 -  Heart disease, as determined by symptomatic congestive heart failure, radionuclide
 ventriculogram (RVG), or echocardiogram-determined LVEF of less than 50%, active
 angina pectoris, or uncontrolled high blood pressure

 -  Pulmonary disease, as determined by severe chronic obstructive lung disease,
 symptomatic restrictive lung disease, or corrected DLCO of less than 50% of predicted
 value

 -  Kidney disease, as determined by serum creatinine levels greater than 2.0 mg/dl

 -  Liver disease, as determined by serum bilirubin levels greater than 2.0 mg/dl (except
 in the case of Gilbert's syndrome or hemolytic anemia in which the bilirubin can be
 elevated greater than 2.0mg/dl), SGOT or SGPT greater than 3 times the upper limit of
 normal

 -  Neurologic disease, as determined by symptomatic leukoencephalopathy, active central
 nervous system (CNS) cancer, or other neuropsychiatric abnormalities that may prevent
 transplantation (previous CNS cancer and presently in CR is acceptable)

 -  HIV antibodies

 -  Uncontrolled infection

 -  Pregnant or breastfeeding