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

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00393380

Enrollment

Registered

2006-10-27

Start date

2006-09-30

Completion date

2012-03-31

Last updated

2013-04-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

Myelogenous Leukemia, Chronic, Myelodysplasia, Parathyroid Hormone, Umbilical Cord Blood Stem Cell Transplantation

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.

Interventions

DRUGParathyroid Hormone (teriparatide)

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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.	Median time to neutrophil engraftment (defined as an absolute neutrophil count \[ANC\] greater than 500)

Secondary

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

Countries

United States

Participant flow

Recruitment details

Thirteen patients were enrolled on the study between October 25, 2006 and March 27, 2008 from three centers. Dana Farber Cancer Institute enrolled 10 patients, University of Florida enrolled 2 patients and Massachusetts General Hospital enrolled 1 patient.

Pre-assignment details

Thirteen patients who were enrolled proceeded to the cord blood transplant.

Participants by arm

Arm	Count
Parathyroid Hormone (Teriparatide) Parathyroid hormone after double umbilical cord blood transplant.	13
Total	13

Baseline characteristics

Characteristic	Parathyroid Hormone (Teriparatide)
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	2 Participants
Age, Categorical Between 18 and 65 years	11 Participants
Age Continuous	39 years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	10 Participants
Region of Enrollment United States	13 participants
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	8 / 13
serious Total, serious adverse events	8 / 13

Outcome results

Primary

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)

Time frame: Statistic is calculated at Day 42 but ANC counts are measured daily up through discharge.

Population: 13 patients received the transplant.

Arm	Measure	Value (MEDIAN)
Parathyroid Hormone (Teriparatide)	Median Time to Neutrophil Engraftment (Defined as an Absolute Neutrophil Count [ANC] Greater Than 500)	30 days

Secondary

100-day Transplant-related Mortality

100-day transplant-related mortality

Time frame: Measured at Day 100

Population: 13 patients were transplanted

Arm	Measure	Value (NUMBER)
Parathyroid Hormone (Teriparatide)	100-day Transplant-related Mortality	4 participants

Secondary

Cumulative Incidence of Acute GVHD Grades II-IV at Day 100

Cumulative Incidence of Acute GVHD Grades II-IV at day 100

Time frame: Measured at Day 100

Population: 13 patients were transplanted

Arm	Measure	Value (NUMBER)
Parathyroid Hormone (Teriparatide)	Cumulative Incidence of Acute GVHD Grades II-IV at Day 100	38.5 percentage of participants

Secondary