Study of Parathyroid Hormone Following Sequential Cord Blood Transplantation From an Unrelated Donor

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Study of Parathyroid Hormone Following Myeloablative Sequential Unrelated Cord Blood Transplantation

Conditions
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Leukemia, Myeloid, Chronic, Anemia, Aplastic, Myelofibrosis, Lymphoma, Hodgkin Disease, Leukemia, Lymphocytic, Chronic, Leukemia, Myelocytic, Acute, Leukemia, Lymphocytic, Acute

Intervention / Treatment
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* Drug: Parathyroid Hormone (teriparatide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One of the following diagnoses: Chronic myelogenous leukemia (CML) accelerated phase or second stable phase; individuals in the first chronic phase are eligible if they have resistance to imatinib Myelodysplasia Aplastic anemia that is not responding to immunosuppressive therapy Myelofibrosis, either primary or secondary to polycythemia vera Relapsed lymphoma or Hodgkin's disease Stage III/IV chronic lymphocytic leukemia (CLL), relapsed after or refractory to at least one fludarabine containing regimen 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parathyroid Hormone (teriparatide)<br>Parathyroid hormone after double umbilical cord blood transplant. | Drug: Parathyroid Hormone (teriparatide)<br>* Day +1: PTH 40 mcg, Day +2: PTH 60 mcg, Day +3: PTH 80 mcg, Day +4 to Day +29 or until ANC>2000/microL: PTH 100 mcg<br>* Other names: teriparatide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Neutrophil Engraftment (Defined as an Absolute Neutrophil Count [ANC] Greater Than 500) | Median time to neutrophil engraftment (defined as an absolute neutrophil count [ANC] greater than 500) | Statistic is calculated at Day 42 but ANC counts are measured daily up through discharge. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Incidence of Acute GVHD Grades II-IV at Day 100 | Cumulative Incidence of Acute GVHD Grades II-IV at day 100 | Measured at Day 100 | 
| Cumulative Incidence of Chronic GVHD | Cumulative Incidence of Chronic GVHD | Measured at 2 years | 
| Platelet Engraftment (Greater Than 20,000) | Platelet engraftment (greater than 20,000) | Measured at Day 180 | 
| 100-day Transplant-related Mortality | 100-day transplant-related mortality | Measured at Day 100 | 
| Cumulative Incidence of Relapse | Cumulative Incidence of Relapse | Measured at 2 years | 
| Overall Survival | Overall Survival | Measured at 2 years | 
| Disease-free Survival | Disease-free survival | Measured at 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelogenous Leukemia, Chronic, Myelodysplasia, Parathyroid Hormone, Umbilical Cord Blood Stem Cell Transplantation