Clinical trial NCT02660281: URMC Related Haplo-identical Donor BMT
Official title: Haploidentical Donor Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hematological Disease
Immune Deficiencies
Solid Tumors
Myelofibrosis
Multiple Myeloma
Lymphoma
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2016-01-21
Enrollment: 74
Sex: ALL
Minimum age (years): 6
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will be a single-center treatment protocol, designed to validate the process of related donor haploidentical-SCT at the Wilmot Cancer Institute Blood and Marrow Transplant Unit.

Detailed description: This study will be a single-center treatment protocol with five possible preparative regimens, designed to validate the process of related donor haploidentical-SCT at the Wilmot Cancer Institute Blood and Marrow Transplant Unit. Enrolled patients will receive chemotherapy +/- radiation as a pre-transplant conditioning regimen. Patients will then receive haploidentical stem cells, either bone marrow or mobilized peripheral blood, followed by GvHD prophylaxis that will include cyclophosphamide. Multiple data points will be collected prior to, during, and following transplantation to ensure safety of the process and to evaluate the stated objectives.

Eligibility criteria: Inclusion Criteria:

Patient Age:

* Pediatric (ages 6 months to 18 years)
* Adult (ages 18-75 years)

Disease:

Congenital and Other Non-malignant Disorders

* Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome)
* Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital Osteopetrosis, Osteogenesis Imperfecta)
* Metabolic disorders (e.g. Hurler's Syndrome)
* Hemoglobinopathies (e.g. Sickle Cell Disease, Thalassemia)
* Severe aplastic anemia

High-Risk Leukemias

Acute Myelogenous Leukemia

* Refractory to standard induction therapy (more than 1 cycle required to achieve remission)
* Recurrent (in CR≥2)
* Treatment-related AML or MDS
* Evolved from myelodysplastic syndrome
* Presence of Flt3 abnormalities
* FAB M6 or M7
* Adverse cytogenetics

Myelodysplastic Syndrome

Acute Lymphoblastic Leukemia including T lymphoblastic leukemia

* Refractory to standard induction therapy (time to CR \>4 weeks)
* Recurrent (in CR ≥2)
* WBC count \>30,000/mcL at diagnosis
* Age \>30 at diagnosis
* Adverse cytogenetics, such as (t(9:22), t(1:19), t(4:11), other MLL rearrangements.

Chronic Myelogenous Leukemia in accelerated phase or blast crisis

Biphenotypic or undifferentiated leukemia

Burkitt's leukemia or lymphoma

Lymphoma:

* Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemosensitive, and ineligible for an autologous stem cell transplant or previously treated with autologous SCT
* Marginal zone or follicular lymphoma that is progressive after at least two prior therapies

Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible for an autologous HSCT

Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and disease status

Graft failure following prior related donor, unrelated donor or UCB transplant

Myelofibrosis

Exclusion Criteria:

1. Patient Age below 6 months or over 75 years
2. Availability of a 10/10 HLA-matched related or unrelated donor within a reasonable time-frame dictated by the clinical urgency of the transplant
3. Autologous HSCT \< 6 months prior to proposed haplo-SCT
4. Pregnant or breast-feeding
5. Current uncontrolled infection
6. Evidence of HIV infection or positive HIV serology
7. Anti-donor HLA antibodies with positive crossmatch and unsuccessful -

Primary outcomes:
measure: The number of days from the date of the stem cell infusion to engraftment of absolute neutrophils (ANC) and platelets (PLT) will be determined based on daily CBC and differential counts.
timeFrame: 42 days following the infusion of stem cells for ANC. [If engraftment of ANC does not occur within 42 days, a subsequent transplant will be performed if a donor is available.
measure: Rate of non-engraftment and secondary graft failure
timeFrame: At 100 days, 6 months, and yearly after transplant from the date of transplant until the date of documented graft failure or the subject's date of death up to 120 months.
Secondary outcomes:
measure: Percentage of subjects who develop acute graft-versus-host disease.
timeFrame: 100 days following the infusion of stem cells
measure: Assess the Maximum Overall Grades 0- IV of acute GvHD and Maximum Severity (0-4) by involved organ system in patients who develop acute graft-versus-host disease.
timeFrame: 100 days following the infusion of stem cells
measure: Percentage of subjects who develop chronic graft-versus-host disease.
timeFrame: Minimally at intervals of 100 days, 6 months and then yearly following the infusion of stem cells until the subject's date of death.or up to 120 months.
measure: Assess the Maximum Grade: Limited versus Extensive; Maximum Severity: Mild, Moderate or Severe) of chronic GvHD in patients who develop chronic graft-versus-
timeFrame: Minimally at intervals of 100 days, 6 months and then yearly following the infusion of stem cells until the subject's date of death or up to 120 months.
measure: Disease-free survival
timeFrame: Disease assessments are performed and reported at time points that include 100 days, 6 months, and yearly until documented progression of disease or the date of death or up to 120 months.
measure: Time to relapsed disease
timeFrame: Disease assessments are performed and reported at time points that include 100 days, 6 months, and yearly until the date of documented progression or the subject's date of death or up to 120 months.
measure: Immune reconstitution
timeFrame: At 100 day, 6 month and one year intervals following the infusion of stem cells until the subject's date of death or up to 120 months.
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Wilmot Cancer Institute
state: New York
Study officials:
affiliation: Wilmot Cancer Center
name: Jeffrey Andolina, MD
role: PRINCIPAL_INVESTIGATOR
References: