Use of Haploidentical Related Donors for Patients Without Matched Sibling, Unrelated Donor or Cord Blood Units

The administration of high-dose chemotherapy followed by the infusion of blood or bone marrow stem cells (stem cell transplantation) from a matched donor has become standard treatment for patients with high-risk or relapsed hematological cancers. Currently, donors are found for approximately 80% of people who require such treatment, although the chance of finding a donor is much lower in some ethnic communities. In the current study the investigators will offer patients requiring transplantation, but for whom well matched donors cannot be identified either from within the family or on the donor registry, a transplant from a half-matched (haploidentical) family member. A myeloablative conditioning regimen and un-manipulated peripheral blood stem cells will be used. Post-transplant cyclophosphamide, tacrolimus and mycophenolate mofetil will be used to prevent graft versus host disease (GVHD). The primary outcome measure will be 6 month survival free from graft failure, relapse and grade 3-4 acute GVHD. Other outcomes of interest will include the frequency of Cytomegalovirus (CMV) or Epstein-Barr Virus (EBV) requiring treatment, overall survival and progression-free survival.

Study Overview

• Status: Completed
• Conditions: Hematologic Neoplasms
• Intervention / Treatment: Procedure: T-Cell replete haplo-transplant

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Foothills Medical Center / Tom Baker Cancer Center
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Center
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• A hematological malignancy such as acute leukemia or myelodysplastic syndrome requiring hematopoietic stem cell transplantation.
• A haploidentical family member willing to donate.
• Suitable performance status, organ function (as defined locally) and disease status for transplantation.
• Patients with acute leukemia must be in morphological complete remission. Patients with chronic myelogenous leukemia must be in chronic phase and those with lymphoma must have chemosensitive disease (at least partial remission to most recent chemotherapy regimen).
• Given written, informed consent to participate in a clinical trial.

Exclusion Criteria:

• An 8/8 matched sibling donor or matched unrelated donor (based on high-resolution typing as appropriate), available within a time frame acceptable to the treating physician
• Patients with an available single allele or single antigen mismatched donor (7/8 or 9/10) or available cord blood donor can be included at the discretion of the treating team, according to local institutional practice.
• Prior allogeneic transplant
• Any exclusion criteria for allogeneic stem cell transplant, as defined by the program. Examples typically include pregnancy, significant comorbidity, and active uncontrolled infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: T-Cell replete haplo-transplant; Infusion of peripheral blood stem cells from a haploidentical related donor following myeloablative conditioning. Cyclophosphamide, mycophenolate mofetil and tacrolimus will be given for GVHD prophylaxis.

Procedure: T-Cell replete haplo-transplant; Infusion of haploidentical related donor peripheral blood stem cells following myeloablative conditioning (fludarabine 200 mg/m2, busulfan 12.8 mg/kg and total body irradiation (TBI) 400 centigray -or- fludarabine 200 mg/m2, busulfan 9.6 mg/kg). GVHD prophylaxis will be with cyclophosphamide 50 mg/kg/day x 2 on days 3 & 4, mycophenolate mofetil 1 gm p.o. bid days 5 - 35 and tacrolimus (5-15 ug/ml) days 5 - 100.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Six month survival, free from relapse, graft failure and grade III/IV acute GVHD	Six months

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of Grade III/IV Acute Graft Versus Host Disease	Six months
Incidence of Chronic Extensive Graft Versus Host Disease	One year
Cumulative incidence of non-relapse mortality at 1 year	One year
Graft failure rate (ANC < 0.5 and low donor chimerism)	Six months
Overall and Disease Free Survival	One year
Relapse Rate	One year
Patients remaining on immune suppression at 1 year	One year
Incidence of CMV and EBV reactivation requiring treatment	One year

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: The Canadian Blood and Marrow Transplant Group
• Investigators: Principal Investigator: Andrew Daly, MD, University of Calgary; Principal Investigator: Kristjan Paulson, MD, University of Manitoba

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): February 1, 2019
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: July 17, 2015
• First Submitted That Met QC Criteria: July 20, 2015
• First Posted (Estimate): July 21, 2015

Study Record Updates

• Last Update Posted (Actual): April 17, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Hematopoietic Stem Cell Transplantation
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: 26110