Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haplo-HCT

Hematologic Malignancies Clinical Trial

Official title:

Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT) For Patients With Hematologic Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02988466
• Other study ID #: 2016LS092
• Secondary ID: MT2016-15
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 24, 2017
• Est. completion date: December 2024

Study information

• Verified date: May 2023
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single institution phase II study of a reduced intensity conditioning (RIC) followed by a haploidentical hematopoietic cell transplant (haplo-HCT) in persons with diagnosis of hematologic malignancy. Conditioning will consists of fludarabine, cyclophosphamide, melphalan and total body irradiation (TBI) preparative regimen with a melphalan dose reduction for patients ≥55 years old and those with HCT Comorbidity Index (CI) >3. This study uses a two-stage phase II design with accrual goal of 84 patients, using 28 patients separately for arms A, C and D

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 78
• Est. completion date: December 2024
• Est. primary completion date: May 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 75 Years

Eligibility

Inclusion Criteria:

• Karnofsky performance status of =70% or Lansky play score = 70%

• A related haploidentical bone marrow donor with up to 2 or 3 HLA locus-mismatches

• The donor and recipient must be HLA identical for at least one haplotype (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1.

• Adequate liver and renal function

• Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction = 40%

• Diffusion capacity corrected (DLCOcorr) > 40% predicted, and absence of O2 requirements

• > 6 months after prior autologous transplant (if applicable)

• Agrees to use contraception during study treatment

• Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)

• Patients who are HIV+ must have undetectable viral load. All HIV+ patients must be evaluated by Infectious Disease (ID) and a HIV management plan establish prior to transplantation

Exclusion Criteria:

• < 70 years with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor

• Pregnancy or breastfeeding

• Current active and uncontrolled serious infection

• Acute leukemia in morphologic relapse/persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods).

• CML in blast crisis

• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy.

• stable non-bulky disease is acceptable.

• Active central nervous system malignancy

Criteria For Donor Selection:

• Donors must be HLA-haploidentical relatives of the patient, defined as having a shared HLA haplotype between donor and patient at HLA-A, -B, -C, and -DRB1.

• Eligible donors (14-70 years old) include biological children, siblings or half siblings, or parents, able and willing to undergo bone marrow harvesting.

• For donors <18 years, the maximum recipient weight (actual body weight) should not exceed 1.25 times the donor weight (actual body weight)1 In addition, bone marrow product volume should be limited to 20 ml/kg donor weight for donors <18 years.

Related Conditions & MeSH terms

• Hematologic Malignancies
• Hematologic Neoplasms
• Neoplasms

Intervention

Biological:
• Haplo HCT <55 years old
Fludarabine (Flu) Cyclophosphamide (Cy) Melphalan (Mel) Total body irradiation (TBI) Non-T-cell depleted donor bone marrow stem cell infusion Day 0
• Haplo HCT =55 years old
Fludarabine (Flu) Cyclophosphamide (Cy) Melphalan (Mel): Dose reduction by 30% Total body irradiation (TBI) Non-T-cell depleted donor bone marrow stem cell infusion

Drug:
• GVHD Prophylaxis
Cyclophosphamide (Cy) Tacrolimus (Tac) Mycophenolate mofetil (MMF)

Biological:
• Haplo HCT =55 and < 65 years old
Fludarabine (Flu) Cyclophosphamide (Cy) Melphalan (Mel) Total body irradiation (TBI) non-T-cell depleted donor bone marrow stem cells
• Haplo HCT =65 and =75 years old
Fludarabine (Flu) Cyclophosphamide (Cy) Total body irradiation (TBI)

Locations

Country	Name	City	State
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival (DFS)	estimate disease-free survival (DFS) at 1 year post-transplant	1 year
Secondary	Incidence of grade II-IV and grade III-IV acute graft versus-host-disease (GVHD)		day 100
Secondary	Treatment related mortality (TRM)		6 month, 1 and 2 year
Secondary	Relapse incidence		1 and 2 year
Secondary	Incidence of serious fungal and viral infection	post-HCT	at day 100 and 1 year