A Phase II Randomized Controlled Trial Comparing GVHD-Reduction Strategies for Allogeneic Peripheral Blood Transplantation (PBSCT) for Patients With Acute Leukemia or Myelodysplastic Syndrome: Selective Depletion of CD45RA+ Naïve T Cells (TND) vs. Post-Transplantation Cyclophosphamide (PTCy)

Who is this study for? Child to adult patients with Acute Lymphocytic Leukemia or Acute Myelogenous Leukemia
Status: Recruiting
Location: See all (3) locations...
Intervention Type: Radiation, Procedure, Biological, Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

This phase II trial investigates two strategies and how well they work for the reduction of graft versus host disease in patients with acute leukemia or MDS in remission. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Maximum Age: 60
Healthy Volunteers: f
View:

• Patients who are considered appropriate candidates for myeloablative, TBI-containing allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:

‣ Acute lymphocytic leukemia (ALL) in first or subsequent morphological remission (\< 5% marrow blasts by morphology).

⁃ Acute myeloid leukemia (AML) in first or subsequent morphological remission (\< 5% marrow blasts by morphology).

⁃ Other acute leukemia or related neoplasm (including but not limited to 'mixed phenotype' 'biphenotypic', 'acute undifferentiated' or 'ambiguous lineage' acute leukemia, blastic plasmacytoid dendritic cell neoplasm, lymphoblastic lymphoma, Burkitt leukemia/lymphoma, mast cell leukemia, chronic myeloid leukemia \[CML\] with blast crisis or other chronic myeloproliferative neoplasm) in first or subsequent morphological remission (\<5% marrow blasts by morphology).

⁃ Myelodysplastic syndrome (MDS) with a history of excess blasts (≥ approximately 5% in marrow blasts by morphology) and a history of receiving cytoreductive therapy (including but not limited to BCL-2 inhibitors or cytotoxic chemotherapy) within the past 3 months.

• Patient age 1-60 years old (inclusive) at the time of informed consent

‣ Patients aged 1-50 years old (inclusive) are eligible for TBI-based conditioning regimens.

⁃ Patients aged 1-60 years old (inclusive) are eligible for busulfan-based conditioning regimens (with or without TBI 4 Gy).

• Patient with an HLA-matched (HLA-A, B, C, DRB1, and DQB1 matched) related or unrelated donor capable of donating PBSC.

• Recipient informed consent/assent and/or legal guardian permission must be obtained.

• DONOR: HLA-matched related and unrelated donors (HLA-A, B, C, DRB1 and DQB1 matched based on high-resolution typing).

• DONOR: \>= 18 years old.

• DONOR: Willing to donate PBSC.

• DONOR: Matched related donors:

‣ Must give informed consent using the related donor informed consent form.

⁃ Must meet institutional donor eligibility criteria or be ineligible with statement that the donor is a first or second degree relative (exception 21 Code of Federal Regulations \[CFR\] 1271.65(b)(i)).

• DONOR: Matched unrelated donors:

‣ Must consent according to the applicable National Marrow Donor Program (NMDP) donor regulatory requirements.

⁃ Must meet eligibility criteria as defined by the NMDP or be ineligible with statement of urgent medical need (exception 21 CFR 1271.65(b)(iii)).

Locations
United States
Florida
Moffitt Cancer Center
RECRUITING
Tampa
Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
RECRUITING
Pittsburgh
Washington
Fred Hutch/University of Washington Cancer Consortium
RECRUITING
Seattle
Contact Information
Primary
Marie Bleakley
mbleakle@fredhutch.org
206-667-6572
Time Frame
Start Date: 2019-11-19
Estimated Completion Date: 2028-12-31
Participants
Target number of participants: 120
Treatments
Experimental: Arm A1 (TBI, TnD)
Patients undergo TBI BID on days -10 to -7, and receive thiotepa IV over 3 hours on days -6 and -5, fludarabine IV over 30 to 60 minutes on days -6 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, CD34+ enriched CD45RA-depleted donor T-lymphocytes IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Experimental: Arm A2 (busulfan, TnD)
Patients receive fludarabine IV over 30 to 60 minutes on days -6 to -2, busulfan IV over 180 minutes on days -5 to -2, and undergo TBI BID on day -1. Patients also receive tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, CD34+ enriched CD45RA-depleted donor T-lymphocytes IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Experimental: Arm C1 (TBI, PTCy, tacrolimus)
Patients undergo TBI BID on days -4 to -2 or -3 to -1, and receive PBSC IV on day 0. Patients also receive cyclophosphamide IV over 1 to 2 hours on days 3 and 4, and tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day 5. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Experimental: Arm C2 (busulfan, PTCy, tacrolimus)
Patients receive fludarabine IV over 30 to 60 minutes on days -5 to -2, busulfan IV over 180 minutes on days -5 to -2, PBSC IV on day 0, cyclophosphamide IV over 1 to 2 hours on days 3 and 4, and tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day 5. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Experimental: Arm D1 (TBI, tacrolimus, methotrexate) [DISCONTINUED NOVEMBER 2021]
Patients undergo TBI BID on days -6 to -4, and receive cyclophosphamide IV over 1 hour on days -3 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, PBSC IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Experimental: Arm D2 (busulfan, tacrolimus, methotrexate) [DISCONTINUED NOVEMBER 2021]
Patients receive busulfan IV over 180 minutes on days -8 to -5, cyclophosphamide IV over 1 hour on days -3 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, PBSC IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Sponsors
Leads: Fred Hutchinson Cancer Center
Collaborators: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov