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

• Sponsor: The Emmes Company, LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00393380
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 13
• Locations: 4
• Arm: 1
• Duration (Months): 66
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Chronic; Anemia, Aplastic; Myelofibrosis; Lymphoma; Hodgkin Disease; Leukemia, Lymphocytic, Chronic; Leukemia, Myelocytic, Acute; Leukemia, Lymphocytic, Acute	Drug: Parathyroid Hormone (teriparatide)	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase II Study of Parathyroid Hormone Following Myeloablative Sequential Unrelated Cord Blood Transplantation
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Parathyroid Hormone (teriparatide) Parathyroid hormone after double umbilical cord blood transplant.	Drug: Parathyroid 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; Other Names: Parathyroid hormone PTH teriparatide

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. Cumulative Incidence of Chronic GVHD [Measured at 2 years]

   Cumulative Incidence of Chronic GVHD

3. Platelet Engraftment (Greater Than 20,000) [Measured at Day 180]

   Platelet engraftment (greater than 20,000)

4. 100-day Transplant-related Mortality [Measured at Day 100]

   100-day transplant-related mortality

5. Cumulative Incidence of Relapse [Measured at 2 years]

   Cumulative Incidence of Relapse

6. Overall Survival [Measured at 2 years]

   Overall Survival

7. Disease-free Survival [Measured at 1 year]

   Disease-free survival

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainesville	Florida	United States	32610
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• The Emmes Company, LLC
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Karen K. Ballen, MD, Massachusetts General Hospital
• Principal Investigator: Joseph Antin, MD, Dana-Farber Cancer Institute
• Principal Investigator: David Avigan, MD, Beth Israel Deaconess Medical Center
• Principal Investigator: Elizabeth J Shpall, MD, MD Anderson Cancer Research Center
• Principal Investigator: Colleen Delaney, MD, Fred Hutchinson Cancer Center
• Principal Investigator: Ram Kamble, MD, Baylor College of Medicine
• Principal Investigator: Katarzyna Jamieson, M.D., University of Florida
• Principal Investigator: Philip McCarthy, M.D., Roswell Park Cancer Institute
• Principal Investigator: Edward Ball, M.D., University of California, San Diego
• Principal Investigator: Richard Maziarz, M.D., Oregon Health and Science University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: The Emmes Company, LLC
• ClinicalTrials.gov Identifier: NCT00393380
• Other Study ID Numbers: 435; U54HL081030-02; NCT00579722
• First Posted: Oct 27, 2006
• Last Update Posted: Apr 29, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by The Emmes Company, LLC: Myelogenous Leukemia, Chronic; Myelodysplasia; Parathyroid Hormone; Umbilical Cord Blood Stem Cell Transplantation
• Additional relevant MeSH terms: Leukemia; Hodgkin Disease; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Anemia, Aplastic; Teriparatide; Hormones; Parathyroid Hormone

Study Results

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

Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
Period Title: Overall Study
STARTED	13
COMPLETED	13
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
Overall Participants	13
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 84.6%
>=65 years	2 15.4%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	39
Sex: Female, Male (Count of Participants)
Female	6 46.2%
Male	7 53.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 7.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	10 76.9%
More than one race	2 15.4%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Median Time to Neutrophil Engraftment (Defined as an Absolute Neutrophil Count [ANC] Greater Than 500)
Description	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.

Outcome Measure Data

Analysis Population Description

13 patients received the transplant.

Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
Measure Participants	13
Median (Full Range) [days]	30

2. Secondary Outcome

Title	Cumulative Incidence of Acute GVHD Grades II-IV at Day 100
Description	Cumulative Incidence of Acute GVHD Grades II-IV at day 100
Time Frame	Measured at Day 100

Outcome Measure Data

Analysis Population Description

13 patients were transplanted

Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
Measure Participants	13
Number (95% Confidence Interval) [percentage of participants]	38.5 296.2%

3. Secondary Outcome

Title	Cumulative Incidence of Chronic GVHD
Description	Cumulative Incidence of Chronic GVHD
Time Frame	Measured at 2 years

Outcome Measure Data

Analysis Population Description

13 patients were transplanted.

Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
Measure Participants	13
Number (95% Confidence Interval) [percentage of participants]	38.5 296.2%

4. Secondary Outcome

Title	Platelet Engraftment (Greater Than 20,000)
Description	Platelet engraftment (greater than 20,000)
Time Frame	Measured at Day 180

Outcome Measure Data

Analysis Population Description

13 patients were transplanted.

Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
Measure Participants	13
Number (95% Confidence Interval) [percentage of participants]	46.2 355.4%

5. Secondary Outcome

Title	100-day Transplant-related Mortality
Description	100-day transplant-related mortality
Time Frame	Measured at Day 100

Outcome Measure Data

Analysis Population Description

13 patients were transplanted

Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
Measure Participants	13
Number [participants]	4 30.8%

6. Secondary Outcome

Title	Cumulative Incidence of Relapse
Description	Cumulative Incidence of Relapse
Time Frame	Measured at 2 years

Outcome Measure Data

Analysis Population Description

13 patients were transplanted.

Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
Measure Participants	13
Number (95% Confidence Interval) [percentage of participants]	15.4 118.5%

7. Secondary Outcome

Title	Overall Survival
Description	Overall Survival
Time Frame	Measured at 2 years

Outcome Measure Data

Analysis Population Description

13 patients were transplanted.

Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
Measure Participants	13
Number (95% Confidence Interval) [percentage of participants]	38.5 296.2%

8. Secondary Outcome

Title	Disease-free Survival
Description	Disease-free survival
Time Frame	Measured at 1 year

Outcome Measure Data

Analysis Population Description

13 patients were transplanted.

Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
Measure Participants	13
Number (95% Confidence Interval) [percentage of participants]	38.5 296.2%

Adverse Events

Time Frame	2 years
Arm/Group Title	Parathyroid Hormone (Teriparatide)
Arm/Group Description	Parathyroid hormone after double umbilical cord blood transplant.
All Cause Mortality
	Parathyroid Hormone (Teriparatide)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Parathyroid Hormone (Teriparatide)
	Affected / at Risk (%)	# Events
Total	8/13 (61.5%)
General disorders
Death	8/13 (61.5%)	8
Other (Not Including Serious) Adverse Events
	Parathyroid Hormone (Teriparatide)
	Affected / at Risk (%)	# Events
Total	8/13 (61.5%)
General disorders
Death	8/13 (61.5%)	8

Limitations/Caveats

The study was closed prematurely due to early mortality and lack of efficacy.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.