Symptoms and General Pathology

All Conditions

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Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

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Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Lymphoproliferative Disorders

Myeloproliferative Disorders

Leukemia, Prolymphocytic

Primary Myelofibrosis

Bone Marrow Diseases

Precancerous Conditions

Leukemia, B-Cell

Hematologic Diseases

Neoplasms by Histologic Type

Immunoproliferative Disorders

Lymphatic Diseases

Leukemia, Biphenotypic, Acute

Chronic Disease

Disease Attributes

Myelodysplastic-Myeloproliferative Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Tacrolimus

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Melphalan

Mycophenolic Acid

Busulfan

Immunologic Factors

Immunosuppressive Agents

Mesna

Antineoplastic Agents, Alkylating

Alkylating Agents

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Patients Receive:

Patients receive:

Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2

Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.

Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.

First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.

Patients receive:

Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1

Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.

Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.

First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.

Patients receive:

Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4

Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.

Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.

First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.

Patients receive:

Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1

Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.

Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.

First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.

Patients receive:

Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1

Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.

Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.

First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.

Given IV or PO pre-transplant as part of conditioning regimen

Given IV pre-transplant as part of conditioning regimen

Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0

PBSC Hematopoietic Stem Cell Transplantation (HSCT)

Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.

First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.

Post-Transplant Cyclophosphamide

Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post cyclophosphamide.

Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.

Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.

Mycophenolate Mofetil

Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.

Patient Reported Outcomes

Given IV pre transplant as part of conditioning regimen

Administered pre-transplant as part of conditioning regimen

Total-body irradiation

Brandan Butler, MBA

OPTIMIZE Study Team

Monzr AlMalki, MD

Hemant Murthy, MD

Antonio M Jimenez Jimenez, MD

Farhad Khimani, MD

Mahasweta Gooptu, MD

Dipenkumar Modi, MD

Mark Juckett, MD

Ramzi Abboud, MD

Brian Shaffer, MD

Katarzyna Jamieson, MD

Rachel J Cook, M.D.

Shannon McCurdy, MD

Betul Oran, MD

Karen Ballen, M.D.

Karen Ballen, MD

Masumi Ueda Oshima, MD

Sameem Abedin, MD

Steven Devine, MD

Jeffery Auletta, MD

The goal of this clinical trial is to determine the effectiveness of Reduced Dose Post-Transplant Cyclophosphamide (PTCy) in patients with hematologic malignancies after receiving an HLA-Mismatched Unrelated Donor (MMUD) . The main question\[s\] it aims to answer are:

* Does a reduced dose of PTCy reduce the occurrence of infections in the first 100 days after transplant?
* Does a reduced dose of PTCy maintain the same level of protection against Graft Versus Host Disease (GvHD) as the standard dose of PTCy?

HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation With Reduced Dose Post Transplantation Cyclophosphamide GvHD Prophylaxis

A Phase II Study of Reduced Dose Post Transplantation Cyclophosphamide as GvHD Prophylaxis in Adult Patients With Hematologic Malignancies Receiving HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Survival at 100 days without grades 2-3 infections (per BMT CTN grading criteria)

Defined as time interval between date of transplant and death from any cause

Defined as disease relapse or progression, or death by any cause

Defined as death and grades II-III infection (per BMT CTN criteria)

Defined as relapse or progression of underling disease (by 1 year), grade III-IV acute GvHD (by 6 months), chronic GvHD requiring systemic immune suppression (by 1 year), or death by any cause (by 1 year).

Defined as death without evidence of disease progression or recurrence

Defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/mm3 for three consecutive measurements on three different days

Defined as platelet count ≥20,000/mm\^3 or ≥50,000/mm\^3 with no platelet transfusions within seven days.

Primary graft failure is defined as no neutrophil recovery to ≥ 500 cells/mm3 by Day 28 post HCT.

Secondary graft failure is defined as as initial neutrophil count recovery followed by subsequent decline in absolute neutrophil counts \<500 cells/mm3, unresponsive to growth factor therapy, but cannot be explained by infection, disease relapse, or medications.

Defined as percent of donor chimerism via peripheral blood

Defined as cumulative incidence of grades II-IV acute GvHD

Defined as grades 2-3 infection as defined by BMT CTN grading criteria.

Defined as incidence of BK virus hemorrhagic cystitis per BMT CTN grading criteria

Defined as disease relapse or progression from Day 0 to 1-year post-HCT

To tabulate adverse events (AEs, experienced by recipients, defined as grade 3-5 unexpected and grade 5 expected AEs according to CTCAE v5

Defined and graded using the ASTCT grading criteria.

Spots Global Cancer Trial Database for immune system disorders