Fludarabine and 400 CGY Total Body Irradiation for Recipients of HLA-Matched or Mis-Matched Family or Unrelated Donor Hematopoietic Stem Cell Transplants Who Have Rejected Their First Allogeneic Stem Cell Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Colorado Blood Cancer Institute
Sponsor:
Information provided by (Responsible Party):
Peter McSweeney, M.D., Colorado Blood Cancer Institute
ClinicalTrials.gov Identifier:
NCT00472329
First received: May 10, 2007
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

Major Objectives A. To determine whether stable allogeneic hematopoietic engraftment can be safely established in patients who have rejected (<5% T Cell Chimerism) a previous allogeneic hematopoietic stem cell graft by using an allogeneic SCT from an HLA-Identical or non-identical family donor or unrelated donors, with fludarabine (150mg/m2) and TBI (400cGy), with post-transplantation immunosuppression utilizing tacrolimus and MMF.

B. To evaluate the incidence of transplant related mortality.

Minor Objectives A. To evaluate the incidence of acute and chronic GVHD after second allogeneic HCT utilizing Tac/MMF with peripheral blood stem cells from matched or mis-matched allogeneic donors.

B. To evaluate disease responses and survival after second allogeneic SCT. C. To evaluate the need for DLI after second transplant for either disease control or persistent mixed chimerism.


Condition Intervention Phase
Graft Failure
Procedure: Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors
Drug: fludarabine
Procedure: TBI
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Fludarabine and 400 CGY Total Body Irradiation for Recipients of HLA-Matched or Mis-Matched Family or Unrelated Donor Hematopoietic Stem Cell Transplants Who Have Rejected Their First Allogeneic Stem Cell Transplant

Resource links provided by NLM:


Further study details as provided by Colorado Blood Cancer Institute:

Primary Outcome Measures:
  • Stable allogeneic hematopoietic engraftment with fludarabine (150mg/m2) and TBI (400cGy), with post-transplantation immunosuppression utilizing tacrolimus and MMF. [ Time Frame: Overall disease free survival ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of acute and chronic GVHD after second allogeneic HCT utilizing Tac/MMF with peripheral blood stem cells from matched or mis-matched allogeneic donors, disease responses and survival after second allogeneic SCT. [ Time Frame: Overall management of acute and chronic GVHD ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: March 2007
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Fludarabine and 400cGY TBI Procedure: Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors Drug: fludarabine Procedure: TBI

Detailed Description:

This protocol will evaluate the use of Fludarabine (150mg/m2) with TBI (400cGy) as pre-transplant conditioning for a second allogeneic stem cell transplant after initial graft rejection. Preliminary data suggest that the combination of Flu/TBI at the proposed doses is safer and more effective than prior second transplantation regimens published to date. As we perform more non-myeloablative transplantations we expect that this issue to arise more frequently. The preliminary data available indicate that the proposed regimen is the safest and most effective to instill donor hematopoiesis after the initial graft has been rejected.

We also wish to evaluate the safety and effectiveness of Tacrolimus and MMF as GVHD prophylaxis in patients receiving a second transplant. Tac/MMF is our current GVHD prophylaxis regimen. It has proven to be well tolerated and provide good protection against GVHD, even in heavily pretreated patients. We propose to use this standard first transplant GVHD prophylaxis to prevent GVHD after second transplantation. DLI may be given in the presence of disease progression or for mixed chimerism as clinically indicated.

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Any patient who has rejected a previous allogeneic transplant (related or unrelated) rejection based on chimerism data from peripheral blood specimens showing loss of donor T Cells.

  1. Available HLA-identical, a one-antigen mis-matched sibling donor, a phenotypically HLA-matched family member, a phenotypically matched unrelated donor, or a 9/10 matched unrelated donor with a negative cross-match.
  2. Age ≤ 75 years.
  3. Patients who fail to engraft or have signs of early relapse after an autologous transplant may be considered for this protocol as salvage treatment if they are presented to the RMBMTP Clinical Care meeting and the majority of the group agrees that this a reasonable treatment option.

Exclusion Criteria:

  1. Patients whose low donor chimerism is felt to be due to rapidly progressive hematological malignancies, unless they can be treated into a minimal disease state with additional treatment.
  2. Patients with active uncontrolled CNS involvement with malignancy.
  3. Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
  4. Females who are pregnant.
  5. Patients who are HIV positive
  6. Organ dysfunction felt to be due to the conditioning for the first transplant including the following:

    • Left ventricle ejection fraction < 35%.
    • DLCO <35% of predicted, or receiving continuous supplementary oxygen.
    • Karnofsky score <50 for patients < 60 years, or <70 for patients aged 60 - 69 years (see appendix B).
    • Creatinine clearance < 40 ml/min.
    • Patients with these end-organ toxicities may be presented to the RMBMTP Patient Care Conference. If the majority opinion is that this treatment is the safest option for a patient who has rejected their first transplant, they will be allowed to undergo the treatment, after informed consent has been signed.

      • Patients with a positive PRA or anti-donor T or B cell (+) will be considered for this treatment protocol only if no other option is available. They should not be eligible for another research study. The transplantation group must have a majority opinion that this is the best available option for the patient in question. In patients with either condition, the only acceptable stem cell source will be peripheral blood.
  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: NCT00472329

Contacts
Contact: Juli Murphy 303-285-5087 Juli.Murphy@usoncology.com
Contact: Nicole Stephens 303-336-2183 Nicole.Stephens@usoncology.com

Locations
United States, Colorado
Rocky Mountain Blood and Marrow Transplant Program Recruiting
Denver, Colorado, United States, 80218
Contact: Juli Murphy    303-285-5087    Juli.Murphy@usoncology.com   
Contact: Nicole Stephens    303-336-2183    Nicole.Stephens@usoncology.com   
Principal Investigator: Mark W Brunvand, MD         
Sub-Investigator: Robert M Rifkin, MD         
Sub-Investigator: Jeffrey V Matous, MD         
Sub-Investigator: Peter A McSweeney, MD         
Sub-Investigator: Scott I Bearman, MD         
Sub-Investigator: Michael B Maris, MD         
Sponsors and Collaborators
Colorado Blood Cancer Institute
Investigators
Principal Investigator: Mark W Brunvand, MD Colorado Blood Cancer Institute
  More Information

No publications provided

Responsible Party: Peter McSweeney, M.D., Principal Investigator, Colorado Blood Cancer Institute
ClinicalTrials.gov Identifier: NCT00472329     History of Changes
Other Study ID Numbers: RMBMT-166-A, CBCI-166
Study First Received: May 10, 2007
Last Updated: June 26, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Fludarabine
Fludarabine phosphate
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014