Treatment of Graft Failure After Hematopoietic Stem Cell Transplantation

This is a guideline for the treatment of graft failure after hematopoietic stem cell transplant (HSCT). This regimen, consisting of cyclophosphamide and fludarabine with low dose total body irradiation (TBI) is designed to promote donor engraftment by day 42 after initial graft failure.

The graft will consist of bone marrow or G-CSF mobilized peripheral blood from a haploidentical related donor. The source of stem cells will be determined by the transplant team based on factors such as patient's age, medical history, donor availability and will be according to the current University of Minnesota Blood and Marrow Transplantation Program selection guidelines.

Study Overview

• Status: Recruiting
• Conditions: Primary Graft Failure; Secondary Graft Failure
• Intervention / Treatment: Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Irradiation; Biological: Hematopoietic stem cell infusion

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Timothy Krepski; Phone Number: 612-273-2800; Email: tkrepsk1@fairview.org

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota Medical Center, Fairview
      • Contact: Timothy Krepski; Phone Number: 612-273-2800; Email: tkrepsk1@fairview.org
      • Principal Investigator: Troy C Lund, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Graft failure for

Description

Inclusion Criteria:

• Patients with primary or secondary graft failure, as defined below, may receive a second transplant:

  • Primary graft failure is defined as not achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42 following the first transplant.
  • Secondary graft failure is defined as achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42, but subsequently drops below 0.5x10^9/L without recovery.
  • Loss of chimerism is defined as achieving an ANC ≥0.5x10^9/L for three consecutive, but with less than 10% CD15+ donor cells in the marrow or peripheral blood.

• Recipients should have acceptable organ function defined as:

  • Renal: creatinine < 2.0 (adults) and creatinine clearance > 30. For creatinine clearance < 70, consultation with a BMT pharmacist is necessary for chemotherapy dose adjustments.
  • Hepatic: bilirubin, AST/ALT, ALP < 10 x upper limit of normal
  • Cardiac: left ventricular ejection fraction > 40%

Exclusion Criteria:

• Uncontrolled infection at the time of transplant.
• Patients with Fanconi Anemia or other DNA breakage syndromes.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Treatment; This regimen consists of cyclophosphamide and fludarabine with low dose total body irradiation (TBI), followed by hematopoietic stem cell infusion.

Drug: Fludarabine; Fludarabine 30 mg/m2 IV over 1 hour given on days -6 through -2 of transplant.; Other Names: Fludara; Drug: Cyclophosphamide; Cyclophosphamide 14.5 mg/kg IV over 1-2 hours given on days -6 and -5 from transplant. And Cyclophosphamide 50 mg/kg IV over 2 hours given on days +3 and +4 from transplant.; Radiation: Total Body Irradiation; TBI 200cGy in a single fraction on day -1 from transplant.; Other Names: TBI; Biological: Hematopoietic stem cell infusion; Hematopoietic stem cell infusion given on day 0.; Other Names: HSCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of donor engraftment	Rate of sustained donor engraftment at day 42 post this transplant.	day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of treatment related mortality	Rate of treatment related mortality (TRM) at day 100	day 100
Rate of survival	Rate of survival by day 100.	Day 100
Rate of survival	Rate of survival at 1 year	1 year
Incidence of acute graft-versus-host disease	Incidence of acute graft-versus-host disease by day 100	Day 100
Incidence of chronic graft-versus-host disease	Incidence of chronic graft-versus-host disease at 1 year.	1 year

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Troy C Lund, MD, PhD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2014
• Primary Completion (Estimated): January 24, 2032
• Study Completion (Estimated): January 30, 2032

Study Registration Dates

• First Submitted: June 10, 2014
• First Submitted That Met QC Criteria: June 10, 2014
• First Posted (Estimated): June 12, 2014

Study Record Updates

• Last Update Posted (Estimated): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Hematopoietic stem cell transplant
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: 2013OC003; MT2013-06C (Other Identifier: University of Minnesota Blood and Marrow Transplant Program)