Reduced Intensity, Sequential Double Umbilical Cord Blood Transplantation Using Prostaglandin E2 (PGE2) - Full Text View

Purpose

The purpose of this research study is to determine the effects of 16, 16 Dimethyl-Prostaglandin E2 (dmPGE2) treatment on umbilical cord blood units to be used in transplantation. dmPGE2 treatment is being tested to see if it can improve the ability of umbilical cord blood stem cells to grow after transplantation. The growth of stem cells after transplantation is sometimes referred to as "engraftment". One of the major problems after umbilical cord transplantation is the time required for engraftment. After transplantation of two umbilical cord blood units, the average time to achieve engraftment is 21 days. In addition, up to 10% of patients who undergo umbilical cord blood transplantation never engraft, a potentially life-threatening condition. In laboratory studies, treatment of umbilical cord blood stem cells with dmPGE2 was shown to enhance engraftment.

Condition	Intervention	Phase
Hematologic Malignancies Allogeneic Stem Cell Transplantation	Drug: Fludarabine Drug: Melphalan Drug: Antithymocyte Globulin Drug: Sirolimus Drug: Tacrolimus Other: Ex-vivo 16, 16 dimethyl-prostaglandin E2 expansion	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Study of Reduced Intensity, Sequential Double Umbilical Cord Blood Transplantation Using Ex-Vivo 16, 16 Dimethyl-Prostaglandin E2 Expanded Umbilical Cord Blood Units

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Melphalan Dinoprostone Melphalan hydrochloride Fludarabine Sirolimus Fludarabine phosphate Tacrolimus Everolimus Temsirolimus Antilymphocyte Serum

U.S. FDA Resources

Further study details as provided by Fate Therapeutics:

Primary Outcome Measures:

Determine the safety of ex-vivo 16, 16 dimethyl-prostaglandin E2-expanded umbilical cord blood units when used for transplantation in a reduced intensity, sequential umbilical cord blood transplantation model. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Time to engraftment of umbilical cord blood units [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Fractional chimerism of transplanted cord blood units [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Rates of acute and chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
30- and 100-day treatment related mortality [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Measures of immune reconstitution and relapse-free and overall survival at 1 and 2 years after transplantation [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	April 2009
Estimated Study Completion Date:	November 2013
Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Group 1 2 umbilical cord units: Second cord blood unit treated with dmPGE2	Drug: Fludarabine 30mg/m2/day IV x 6 days Drug: Melphalan 100 mg/m2/day IV x 1 day Drug: Antithymocyte Globulin 1mg/kg/day x 4 days Drug: Sirolimus GVHD Prophylaxis: Target range 3-12 ng/ml Drug: Tacrolimus GVHD Prophylaxis: Target range 5-10 ng/ml Other: Ex-vivo 16, 16 dimethyl-prostaglandin E2 expansion Thawed cord blood is washed with and resuspended in Dextran/albumin. 16, 16 dimethyl-prostaglandin E2 is added and the mix is incubated for 2 hours.
Active Comparator: Group 2 2 umbilical cord units: First cord blood unit treated with dmPGE2	Drug: Fludarabine 30mg/m2/day IV x 6 days Drug: Melphalan 100 mg/m2/day IV x 1 day Drug: Antithymocyte Globulin 1mg/kg/day x 4 days Drug: Sirolimus GVHD Prophylaxis: Target range 3-12 ng/ml Drug: Tacrolimus GVHD Prophylaxis: Target range 5-10 ng/ml Other: Ex-vivo 16, 16 dimethyl-prostaglandin E2 expansion Thawed cord blood is washed with and resuspended in Dextran/albumin. 16, 16 dimethyl-prostaglandin E2 is added and the mix is incubated for 2 hours.
Active Comparator: Group 3 2 umbilical cord units: First cord blood unit treated with dmPGE2	Drug: Fludarabine 30mg/m2/day IV x 6 days Drug: Melphalan 100 mg/m2/day IV x 1 day Drug: Antithymocyte Globulin 1mg/kg/day x 4 days Drug: Sirolimus GVHD Prophylaxis: Target range 3-12 ng/ml Drug: Tacrolimus GVHD Prophylaxis: Target range 5-10 ng/ml Other: Ex-vivo 16, 16 dimethyl-prostaglandin E2 expansion Thawed cord blood is washed with and resuspended in Dextran/albumin. 16, 16 dimethyl-prostaglandin E2 is added and the mix is incubated for 2 hours.

Detailed Description:

On the day of admission to the hospital, two intravenous catheters will be placed in the large veins in the participant's upper chest underneath the collarbone. The catheters will remain in place throughout the transplant.
The chemotherapy portion of the treatment is called "Conditioning Therapy". The chemotherapy is used to prepare the bone marrow space to receive the transplanted umbilical cord blood units. It consists of three intravenous medications; fludarabine, melphalan and antithymocyte globulin or thymoglobulin.
Starting three days before transplant and every day for 6-9 months after the transplant, participants will receive the immune suppressive drugs tacrolimus and sirolimus. These drugs are used to prevent Graft-Vs.-Host-Disease (GVHD), which might develop as the transplant engrafts.
After the participant completes the "Conditioning Therapy", they will have their transplant. The day of the transplant is referred to as Day 0. On the day of the transplant, each cord blood unit will be thawed and washed in the laboratory and be given through the central venous catheter. All participants receive 2 cord blood units 2-5 hours apart.
As part of this research study some cord units will be treated in the laboratory with dmPGE2 before it is given to the participant. 3 different dmPGE2 treatment groups will be tested. Group 1: will have the second cord blood unit treated; Group 2: will have their first cord blood unit treated and; Group 3 will expand the experience of treating the first cord blood unit. The three groups will be treated sequentially. If the treatment strategy in Group 1 is deemed to be safe, Group 2 will be treated. If there is evidence that the treated umbilical cord blood units from Groups 1 and 2 are engrafting, and that the treatment is safe, Group 3 will be tested.
Participants will also be treated with antibiotics to prevent and treat infection. They may also receive transfusions of red blood cells and platelets. To help with engraftment, they will be given the drug G-CSF (Neupogen) starting five days after the transplant and until their white blood cells recover.
After participants leave the hospital, they will be required to come back for monitoring and routine care very frequently. This is standard after umbilical cord blood transplantation.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with hematologic malignancies for whom allogeneic stem cell transplantation is deemed clinically appropriate
Patient must be ineligible for traditional myeloablative transplantation according to treating physician
Lack of 6/6 or 5/6 HLA-matched related, 8/8 HLA-matched unrelated donor, or unrelated donor not available within a time frame necessary to perform a potentially curative stem cell transplant
18-65 years of age
ECOG Performance Status 0-2

Exclusion Criteria:

The following hematologic malignancies are excluded:
- Myelofibrosis unless there has been exposure to cytotoxic chemotherapy for the treatment of progression to acute myeloid leukemia
- Chronic Myelogenous Leukemia, unless there has been exposure to cytotoxic chemotherapy for the treatment of blast phase, 3) Aplastic anemia, in the absence of transformation to Myelodysplastic disorder
Cardiac disease: symptomatic congestive heart failure or evidence of left ventricular dysfunction as measured by gated radionucleotide ventriculogram or echocardiogram; active angina pectoris, or uncontrolled hypertension
Pulmonary disease: symptomatic chronic obstructive lung disease, symptomatic restrictive lung disease, or corrected DLCO of < 50% of predicted, corrected hemoglobin
Renal disease: serum creatinine > 2.0mg/dl
Hepatic disease: serum bilirubin > 2.0mg/dl (expect in the case of Gilbert's syndrome or ongoing hemolytic anemia), SGOT or SGPT > 3 x upper limit of normal
Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation
HIV antibody
Uncontrolled infection
Pregnancy or breast feeding mother
Inability to comply with the requirements for care after allogeneic stem cell transplantation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00890500

Locations

United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Fate Therapeutics

Brigham and Women's Hospital

Massachusetts General Hospital

Harvard University

Dana-Farber Cancer Institute

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Corey Cutler, MD, MPH, FRCP(C)

Dana-Farber Cancer Institute

More Information

No publications provided

Responsible Party:	Fate Therapeutics
ClinicalTrials.gov Identifier:	NCT00890500 History of Changes
Other Study ID Numbers:	08-274
Study First Received:	April 28, 2009
Last Updated:	March 7, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Antilymphocyte Serum
Melphalan
Fludarabine monophosphate
Sirolimus
Tacrolimus
Dinoprostone
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

Oxytocics
Reproductive Control Agents
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antibiotics, Antineoplastic
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 21, 2013