Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplant

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
David Rizzieri, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00597714
First received: January 14, 2008
Last updated: September 6, 2013
Last verified: September 2013
  Purpose

The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free, and overall survival rates in patients treated with alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing.


Condition Intervention Phase
Hodgkin's Disease
Non Hodgkin's Lymphoma
Myeloma
Leukemia
Myelodysplasia
Drug: Non-myeloablative Stem Cell Transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Estimate toxicity, disease free, progression free and overall survival rates in patients treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate immune recovery following this reduced intensity allogeneic immunotherapy. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • Develop an in vitro assay to allow patient individualized targeted dosing for busulfan [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 189
Study Start Date: February 2008
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohorts A and B

Group A: Patients with a high chance of progressive lymphoid or myelomatous disease.

Group B: Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders.

Drug: Non-myeloablative Stem Cell Transplantation
Donor will receive G-CSF 8 mcg/kg/d subcutaneously bid for 4 days, until pheresis is completed or until WBC is > 100,000. Recipients in both cohorts will be premedicated with Benadryl 50 mg IV or PO, and acetaminophen 650 mg orally (or hydrocortisone 50-100 mg IV on first day). The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. For the Group B cohort, the prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The PBSCs will be infused over 2-4 days. Patient evaluations will occur 2 times per week by physical exam for toxicity through day 45.
Other Name: Allogeneic Stem Cell Transplant

Detailed Description:

The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free and overall survival rates in patients treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing. The study population is HIV negative, adult patients who are not pregnant but have confirmed diagnosis of disease; must have CALGB PS 0, 1, or 2; must have a 3-6/6 HLA-matched related donor or 8/8 (A, B, C, DRB1, DQ are the primary determinants) or better HLA-matched unrelated donor who is evaluated and deemed able to provide PBPCs and/or marrow by the transplant team. The target population of patients is those with a high chance of progressive lymphoid or myelomatous diseases, progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have their diagnosis confirmed at the transplant center.
  • Performance status must be CALGB PS 0, 1, or 2.
  • Patients must have a 3-6/6 HLA-matched related donor or 8/8 or better allele level match MUD matched unrelated donor (at A,B, C, DRB1, DQ).
  • HIV negative.
  • Women of child bearing potential must have a negative pregnancy serum beta-HCG test within 1 week of starting therapy.
  • Patients > or equal to 18 years of age are eligible.
  • Patients must have a MUGA and/or ECHO or cardiac MR and PFTs with DLCO performed before transplant.
  • Specific patient populations:

    • Group A) Patients with a high chance of progressive lymphoid or myelomatous diseases.
    • Group B) Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders

Exclusion Criteria:

  • Pregnant or lactating women.
  • Patients with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol.
  • Patients with uncontrolled, progressive infections.
  • Patients who are good candidates for long term disease control with standard chemotherapy or radiation or high dose therapy and autologous support.
  • Patients with active CNS disease.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00597714

Locations
United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
David Rizzieri
Investigators
Principal Investigator: David Rizzieri, MD Duke University Health System
  More Information

No publications provided

Responsible Party: David Rizzieri, Associate Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00597714     History of Changes
Other Study ID Numbers: Pro00003567
Study First Received: January 14, 2008
Last Updated: September 6, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Duke University:
Stem Cell Transplantation, Non-myeloablative

Additional relevant MeSH terms:
Hodgkin Disease
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on April 14, 2014