A Trial of Extracorporeal Photopheresis, Pentostatin, and Total Body Irradiation in Patients Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation for the Treatment of Malignancies

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2009 by Yale University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Hospira, Inc.
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00402714
First received: November 20, 2006
Last updated: April 28, 2009
Last verified: April 2009
  Purpose

This is a study to explore the use of a reduced intensity transplant conditioning regimen. A conditioning regimen is the treatment that is given to prepare a body for the new bone marrow that will be received from a donor. Reduced intensity conditioning uses lower doses of chemotherapy than conventional conditioning regimens. The use of lower doses of drugs and radiation cause fewer side effects. Reduced intensity regimens have been offered to older patients or patients at increased risk for transplant-related side effects and have been shown to be safe and effective. Reduced intensity conditioning regimens are now considered for many patients who are undergoing transplant.


Condition Intervention Phase
Hematologic Malignancies
Procedure: extracorporeal photopheresis
Drug: Pentostatin
Radiation: Total Body Irradiation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Trial of Extracorporeal Photopheresis, Pentostatin, and Total Body Irradiation Versus Pentostatin and Total Body Irradiation in Patients Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation for the Treatment of Malignancies

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Incidence of grade 2-4 acute graft versus host disease following allogeneic stem cell transplantation in patients randomized to photopheresis vs. no photopheresis [ Time Frame: Day +100 following allogeneic stem cell transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determining time to neutrophil and platelet engraftment, nonrelapse mortality, disease response, failure free survival, and overall survival [ Time Frame: 2 years following stem cell transplant ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: July 2006
Estimated Study Completion Date: January 2010
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Extracorporeal photopheresis, pentostatin and total body irradiation
Procedure: extracorporeal photopheresis
Extracorporeal photopheresis (ECP) is the ex vivo exposure of the leukocyte rich fraction to ultraviolet light in the presence of 8-methoxypsoralen.
Other Names:
  • UVAR® XTS Photopheresis System
  • UVADEX®
  • 8-methoxypsoralen
  • methoxsalen
Drug: Pentostatin
pentostatin 8mg/m2 over 48 hours by continuous infusion
Other Names:
  • DCF
  • 2-Deoxycoformycin
  • Nipent
Radiation: Total Body Irradiation
600cGy TBI in 3 200cGy TBI fractions
Active Comparator: 2
Pentostatin and total body irradiation
Drug: Pentostatin
pentostatin 8mg/m2 over 48 hours by continuous infusion
Other Names:
  • DCF
  • 2-Deoxycoformycin
  • Nipent
Radiation: Total Body Irradiation
600cGy TBI in 3 200cGy TBI fractions

Detailed Description:

One of the complications of allogeneic stem cell transplant (ASCT) is graft versus host disease (GVHD). This is when the donor cells that are infused attack the body organs. This can cause serious illness and even death. The chance of getting serious life threatening GVHD with conventional transplant conditioning regimens is 25-50% depending on whether the donor bone marrow is from a family member or an unrelated person. The reduced intensity conditioning regimen used in this study involves a drug called pentostatin as well as a reduced dose of radiation and a treatment called photopheresis. This regimen has been successfully used in 106 patients. The incidence of serious GVHD in those patients was much less than expected: 8% for patients getting bone marrow from a family member and 23% for those getting bone marrow from an unrelated person. The pentostatin and radiation parts of this reduced intensity conditioning regimen are similar to other types of reduced intensity regimens, which use drugs similar to pentostatin. The unique part of this regimen compared to others is the use of extracorporeal photopheresis (ECP).

While ECP has been used in 106 patients as part of a reduced intensity conditioning regimen, it is unknown whether adding ECP to pentostatin and radiation is what caused the reduced rate of GVHD that was seen in the previous study that was done. The use of ECP as part of a conditioning regimen is investigational. ECP is approved by the U.S. Food and Drug Administration (FDA) for the treatment of cutaneous T-cell lymphoma, but is not approved by the FDA for use prior to ASCT.

Because it is not known whether the use of ECP in the reduced intensity conditioning regimen was what caused the low incidence of GVHD, this research study will look at differences in getting GVHD based on whether you receive ECP. Half the patients in this research study will receive ECP as part of their reduced intensity-conditioning regimen and the other half will not. Patients will be randomized (50% chance you will receive ECP and 50% chance you will not). Both groups will receive pentostatin and reduced dose total body irradiation. The primary purpose of this research study is to look at the chance of developing serious GVHD within the first 100 days after transplant within each group.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must give informed consent to receive study treatment.
  • Availability of a suitable 5/6 (Class I mismatch) or 6/6 HLA-matched related or 10 or 10 matched unrelated donor.
  • Adequate cardiac function with an ejection fraction ≥ 35% by echocardiography or nuclear cardiography within three months of transplantation
  • Adequate pulmonary function with corrected DLCO ≥ 40% by pulmonary function testing within the past three months of transplantation
  • Adequate renal function with creatinine clearance ≥ 30 ml/min. as calculated by the Cockroft and Gault method.
  • Adequate hepatic function with AST, ALT, alkaline phosphatase, and total bilirubin no more than 3 x ULN unless related to neoplastic disease.
  • Adequate vascular access, either by pheresis flow catheter or peripheral vein intravenous catheter, to perform ECP, should the patient be randomized to ECP.
  • Patients with prior autologous stem cell transplantation are eligible.
  • Age 18 to 75 years.
  • Life expectancy of greater than 3 months.
  • ECOG performance status of 0, 1, or 2.
  • Platelet counts ≥ 20,000/microliter, with or without transfusion support, at the time of ECP, should the patient be randomized to ECP.
  • Weight ≥ 40 kg.
  • Systolic blood pressure ≥ 90 mmHg on the day randomization occurs
  • Negative pregnancy test. The effects of ECP on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Able to receive 600 cGy of total body irradiation. If patient previously treated by TBI then must be able to receive 400cGY of total body irradiation.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Hypersensitivity or allergy to 8-methoxypsoralen.
  • Prior allogeneic stem cell transplantation
  • HLA-DR mismatch or no worse than one antigen-mismatched unrelated donor.
  • Patients with acute leukemia or acute lymphocytic leukemia with > 5% circulating blasts in peripheral blood or > 5% blasts in bone marrow aspirate and biopsy at the time of registration
  • Patients with chemorefractory non-Hodgkin's lymphoma or Hodgkin's disease or multiple myeloma
  • Diagnosis of myelofibrosis
  • Patients known to be positive for antibodies to HIC or have evidence for active HIC viral replication.
  • Participation in another clinical trial for prevention of GVHD.
  • Patient is pregnant or lactating.
  • Lack adequate vascular access for ECP.
  • Systolic blood pressure < 90 mmHg at the time of randomization, should the patient be randomized to ECP.
  • Evidence of active, ongoing infection.
  • Unwilling to comply with all study procedures.
  • Unable or unwilling to give signed informed consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00402714

Contacts
Contact: Donna LaCivita, MPH 203-737-2579 donna.lacivita@yale.edu
Contact: Noelle Sowers, RN 203-785-2442 noelle.sowers@yale.edu

Locations
United States, Connecticut
Yale Comprehensive Cancer Center at Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Donna LaCivita, MPH    203-737-2579    donna.lacivita@yale.edu   
Contact: Noelle Sowers, RN    203-785-2442    noelle.sowers@yale.edu   
Principal Investigator: Francine Foss, M.D.         
United States, Massachusetts
Tufts-New England Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Carrie Grodman, RN    617-636-2682    cgrodman@tufts-nemc.org   
Principal Investigator: Kellie Sprague, MD         
United States, Texas
Methodist Hospital - Texas Transplant Institute Recruiting
San Antonio, Texas, United States, 78229
Contact: Maureen Hougham    210-575-4035    maureen.hougham@MHShealth.com   
Principal Investigator: Paul Shaughnessy, M.D.         
Sponsors and Collaborators
Yale University
Hospira, Inc.
Investigators
Principal Investigator: Francine Foss, M.D. Yale University
  More Information

No publications provided

Responsible Party: Francine Foss, M.D., Principal Investigator, Yale University School of Medicine
ClinicalTrials.gov Identifier: NCT00402714     History of Changes
Other Study ID Numbers: 0508000433
Study First Received: November 20, 2006
Last Updated: April 28, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Allogeneic Stem Cell Transplant

Additional relevant MeSH terms:
Neoplasms
Methoxsalen
Pentostatin
Adenosine Deaminase Inhibitors
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Photosensitizing Agents
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014