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

Phase 2

Terminated

• Conditions: Leukemia, Myeloid, Chronic; Anemia, Aplastic; Myelofibrosis; Lymphoma; Hodgkin Disease; Leukemia, Lymphocytic, Chronic; Leukemia, Myelocytic, Acute; Leukemia, Lymphocytic, Acute
• Interventions: Drug: Parathyroid Hormone (teriparatide)

• Registration Number: NCT00393380
• Lead Sponsor: The Emmes Company, LLC

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.

Study Timeline

• Study Start: 2006-09
• Study First Submitted: 2006-10-25
• Study First Submitted QC: 2006-10-25
• Study First Posted: 2006-10-27
• Primary Completion: 2009-11
• Study Completion: 2012-03
• Results First Submitted: 2012-11-06
• Results First Submitted QC: 2012-11-06
• Results First Posted: 2012-12-07
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-22
• Last Update Posted: 2013-04-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Parathyroid Hormone (teriparatide)	Parathyroid Hormone (teriparatide)	Parathyroid hormone after double umbilical cord blood transplant.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Platelet Engraftment (Greater Than 20,000)	Measured at Day 180	Platelet engraftment (greater than 20,000)
100-day Transplant-related Mortality	Measured at Day 100	100-day transplant-related mortality
Cumulative Incidence of Relapse	Measured at 2 years	Cumulative Incidence of Relapse
Overall Survival	Measured at 2 years	Overall Survival
Disease-free Survival	Measured at 1 year	Disease-free survival

Trial Locations

Locations (4)

University of Florida; 🇺🇸 Gainesville, Florida, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States