Clinical trial NCT00393380: Study of Parathyroid Hormone Following Sequential Cord Blood Transplantation From an Unrelated Donor
Official title: A Phase II Study of Parathyroid Hormone Following Myeloablative Sequential Unrelated Cord Blood Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia, Myeloid, Chronic
Anemia, Aplastic
Myelofibrosis
Lymphoma
Hodgkin Disease
Leukemia, Lymphocytic, Chronic
Leukemia, Myelocytic, Acute
Leukemia, Lymphocytic, Acute
Keywords: Myelogenous Leukemia, Chronic
Myelodysplasia
Parathyroid Hormone
Umbilical Cord Blood Stem Cell Transplantation
Lead sponsor: The Emmes Company, LLC
Sponsor class: INDUSTRY
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2006-10-27
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Median Time to Neutrophil Engraftment (Defined as an Absolute Neutrophil Count [ANC] Greater Than 500)
timeFrame: Statistic is calculated at Day 42 but ANC counts are measured daily up through discharge.
Secondary outcomes:
measure: Cumulative Incidence of Acute GVHD Grades II-IV at Day 100
timeFrame: Measured at Day 100
measure: Cumulative Incidence of Chronic GVHD
timeFrame: Measured at 2 years
measure: Platelet Engraftment (Greater Than 20,000)
timeFrame: Measured at Day 180
measure: 100-day Transplant-related Mortality
timeFrame: Measured at Day 100
measure: Cumulative Incidence of Relapse
timeFrame: Measured at 2 years
measure: Overall Survival
timeFrame: Measured at 2 years
measure: Disease-free Survival
timeFrame: Measured at 1 year
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Karen K. Ballen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dana-Farber Cancer Institute
name: Joseph Antin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beth Israel Deaconess Medical Center
name: David Avigan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MD Anderson Cancer Research Center
name: Elizabeth J Shpall, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fred Hutchinson Cancer Center
name: Colleen Delaney, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor College of Medicine
name: Ram Kamble, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Katarzyna Jamieson, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Roswell Park Cancer Institute
name: Philip McCarthy, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Edward Ball, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Oregon Health and Science University
name: Richard Maziarz, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ballen K, Mendizabal AM, Cutler C, Politikos I, Jamieson K, Shpall EJ, Dey BR, Attar E, McAfee S, Delaney C, McCarthy P, Ball ED, Kamble R, Avigan D, Maziarz RT, Ho VT, Koreth J, Alyea E, Soiffer R, Wingard JR, Boussiotis V, Spitzer TR, Antin JH. Phase II trial of parathyroid hormone after double umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2012 Dec;18(12):1851-8. doi: 10.1016/j.bbmt.2012.06.016. Epub 2012 Jul 2.