Clinical Trial: Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Pilot Trial Of Reduced Intensity Allogeneic Stem Cell Transplantation With Fludarabine, Melphalan, And Low Dose Total Body Irradiation

Brief Summary: This clinical trial is studying how well giving fludarabine phosphate and melphalan together with total-body irradiation followed by donor stem cell transplant works in treating patients with hematologic cancer or bone marrow failure disorders. Giving low doses of chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells or abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect)

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the transplant related mortality (TRM) of this reduced intensity transplantation (RIT) combination in a patient population that is usually not eligible for a full myeloablative allogeneic transplant.

SECONDARY OBJECTIVES:

I. To evaluate engraftment, safety, clinical response, evidence of graft-versus-malignancy effect/graft-versus-host disease (GVHD) and overall outcomes of treatment with our RIT regimen across a variety of hematological conditions.

OUTLINE: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

After completion of study treatment, patients are followed up periodically.


Sponsor: Roswell Park Cancer Institute

Current Primary Outcome: Day 100 TRM [ Time Frame: First 100 days ]

Day 100 Treatment Related Mortality An exact 95% confidence interval will be provided.


Original Primary Outcome: Transplant-related mortality rate by day 100

Current Secondary Outcome:

  • Median Time to ANC Engraftment [ Time Frame: Days 30 ]

    Median Time to ANC Engraftment

    Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.

  • Median Time to Platelet Engraftment [ Time Frame: Day 100 ]

    Median Time to Platelet Engraftment

    Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.

  • Rate of Complete Donor Chimerism - Blood [ Time Frame: Day 30 ]

    Rate of Complete Donor Chimerism - Blood

    Summarized using standard descriptive statistics.

  • Rate of Complete Donor Chimerism - Blood [ Time Frame: Day 100 ]

    Rate of Complete Donor Chimerism - Blood

    Summarized using standard descriptive statistics.

  • Acute GVHD Grade III-IV [ Time Frame: Up to day 100 ]

    Acute GVHD grade III-IV

    Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.

  • 1 yr Extenstive Chronic GVHD [ Time Frame: Up to 4.5 years ]

    1 yr Extensive Chronic GVHD

    Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.

  • 3 yr Overall Survival [ Time Frame: Up to 4.5 years ]
    3 yr Overall Survival estimated using the Kaplan-Meier method.


Original Secondary Outcome:

  • Time to engraftment
  • Safety
  • Clinical response
  • Rate of complete donor chimerism
  • Acute and chronic graft-vs-host disease
  • Overall survival


Information By: Roswell Park Cancer Institute

Dates:
Date Received: March 4, 2009
Date Started: January 2009
Date Completion:
Last Updated: November 28, 2016
Last Verified: November 2016