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

NCT00472329 | Unknown Phase 2

• 2 other identifiers: RMBMT-166-ACBCI-166
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Graft Failure

Outcome Measures

Primary Outcomes (1)

• Stable allogeneic hematopoietic engraftment with fludarabine (150mg/m2) and TBI (400cGy), with post-transplantation immunosuppression utilizing tacrolimus and MMF.

  Overall disease free survival

Secondary Outcomes (1)

• 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.

  Overall management of acute and chronic GVHD

Study Arms (1)

Fludarabine and 400cGY TBI

NO INTERVENTION

Procedure: Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors; Drug: fludarabine; Procedure: TBI

Interventions

Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors PROCEDURE

Fludarabine and 400cGY TBI

fludarabine DRUG

Fludarabine and 400cGY TBI

TBI PROCEDURE

Fludarabine and 400cGY TBI

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Age ≤ 75 years.
• 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.

You may not qualify if:

• 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.
• Patients with active uncontrolled CNS involvement with malignancy.
• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
• Females who are pregnant.
• Patients who are HIV positive
• 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.

Sponsors & Collaborators

• Colorado Blood Cancer Institute: lead

Study Sites (1)

Rocky Mountain Blood and Marrow Transplant Program

Denver, Colorado, 80218, United States

RECRUITING

MeSH Terms

Interventions

fludarabine

Study Officials

• Mark W Brunvand, MD

  Colorado Blood Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juli Murphy

CONTACT

303-285-5087; Juli.Murphy@usoncology.com

Nicole Stephens

CONTACT

303-336-2183; Nicole.Stephens@usoncology.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 10, 2007
• First Posted: May 11, 2007
• Study Start: March 1, 2007
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: June 30, 2014

Record last verified: 2014-06

Locations

US (1)