Clinical Trial: Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Hematologic Malignancies

Brief Summary: This clinical trial studies reduced-intensity conditioning before donor stem cell transplant in treating patients with high-risk hematologic malignancies. Giving low-doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer 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 cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect.

Detailed Summary:

PRIMARY OBJECTIVE:

1. To compare the rate of disease-free survival (DFS) at 1 year post hematopoietic stem cell transplant (HSCT) in patients undergoing HSCT treated on this successor Thomas Jefferson University (TJU) 2 Step reduced intensity conditioning (RIC) haploidentical regimen and compare it with that of the initial 2 Step RIC regimen.

SECONDARY OBJECTIVES:

  1. To assess the 100 day regimen-related mortality (RRM) in patients undergoing HSCT on this treatment protocol.
  2. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treatment on this regimen.
  3. To evaluate engraftment rates and lymphoid reconstitution in patients treated on this trial.
  4. To assess overall survival at 1 and 3 years past HSCT in patients treated on this trial.

OUTLINE:

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -15 to -12, thiotepa IV over 2 hours on days -15 to -13, donor lymphocyte infusion (DLI) on day -6, and cyclophosphamide IV over 2 hours on days -3 and -2. Patients also undergo total-body irradiation (TBI) on day -10.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and mycophenolate mofetil IV twice daily (BID) on days -1 to 28.

After completion of study treatment, p
Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Current Primary Outcome: Disease-free survival (DFS) [ Time Frame: 1 year ]

The primary null hypothesis is that 1 year DFS rate is at most 35%. 35% is the rounded number (actual 36%) representing the DFS at 1 year of patients treated on the initial TJU 2 Step RIC HSCT trial and consistent with the outcome of patients treated on similar protocols outside of our institution.


Original Primary Outcome: Disease-free survival (DFS) [ Time Frame: 1 year ]

This hypothesis will be rejected if the 95% confidence interval for year DFS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.


Current Secondary Outcome:

  • Overall survival [ Time Frame: 1 year and 3 years ]
  • Incidence of Regimen Related Toxicity [ Time Frame: Up to 1 year ]
    Graded according to the National Cancer Institute (NCI) Common Toxicity Criteria version 4.0
  • Immune reconstitution [ Time Frame: Up to 1 year ]
  • Incidence and degree of GVHD [ Time Frame: Up to 1 year ]
  • Engraftment rates [ Time Frame: Up to 1 year ]


Original Secondary Outcome:

  • Overall survival [ Time Frame: 1 year and 3 years ]
    Will be analyzed and reported descriptively.
  • Incidence of regimen related toxicity graded according to the National Cancer Institute (NCI) Common Toxicity Criteria version 4.0 [ Time Frame: Up to 1 year ]
    Will be analyzed and reported descriptively.
  • Immune reconstitution [ Time Frame: Up to 1 year ]
    Will be analyzed and reported descriptively.
  • Incidence and degree of GVHD [ Time Frame: Up to 1 year ]
    Will be analyzed and reported descriptively.
  • Engraftment rates [ Time Frame: Up to 1 year ]
    Will be analyzed and reported descriptively.


Information By: Thomas Jefferson University

Dates:
Date Received: January 2, 2013
Date Started: December 2012
Date Completion: January 2020
Last Updated: October 19, 2016
Last Verified: October 2016