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

Sponsor:	Fate Therapeutics
Collaborators:	Brigham and Women's Hospital Massachusetts General Hospital Harvard Stem Cell Instutute Dana-Farber Cancer Institute National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	Fate Therapeutics
ClinicalTrials.gov Identifier:	NCT00890500

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 I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Factorial Assignment, Safety Study
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: Fludarabine Sirolimus Fludarabine monophosphate Tacrolimus anhydrous Tacrolimus Melphalan Dinoprostone Sarcolysin Melphalan hydrochloride

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 Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1: Active Comparator 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 1 hour
Group 2: Active Comparator 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 1 hour
Group 3: Active Comparator 2 umbilical cord units: Both cord blood units 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 1 hour
Group 4: Active Comparator 2 umbilical cord units: Both cord blood units 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 1 hour

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. 4 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; Groups 3 and 4 will have both cord blood units treated. The four 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. Group 4 will be treated if Group 3 is safe.
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

Contacts

Contact: Corey Cutler, MD, MPH, FRCP(C)	617-632-5946
Contact: Zena Falk	617-632-6808

Locations

United States, Massachusetts
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Corey Cutler, MD, MPH, FRCP(C)
Massachusetts General Hospital	Not yet recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Karen Ballen, MD

Sponsors and Collaborators

Fate Therapeutics

Brigham and Women's Hospital

Massachusetts General Hospital

Harvard Stem Cell Instutute

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:	Dana-Farber Cancer Institute ( Corey Cutler, MD, MPH, FRCP(C) )
Study ID Numbers:	08-274
Study First Received:	April 28, 2009
Last Updated:	February 2, 2010
ClinicalTrials.gov Identifier:	NCT00890500 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Sirolimus
Melphalan
Anti-Infective Agents
Immunologic Factors
Hematologic Neoplasms
Molecular Mechanisms of Pharmacological Action
Oxytocics
Antineoplastic Agents
Physiological Effects of Drugs
Tacrolimus
Reproductive Control Agents
Antibiotics, Antineoplastic
Anti-Bacterial Agents

Dinoprostone
Neoplasms by Site
Therapeutic Uses
Antifungal Agents
Alkylating Agents
Hematologic Diseases
Immunosuppressive Agents
Pharmacologic Actions
Antilymphocyte Serum
Neoplasms
Myeloablative Agonists
Fludarabine
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on February 08, 2010