Description:
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.
Clinical Trials /
URMC Related Haplo-identical Donor BMT
NCT02660281
Related Conditions:
- Acute Biphenotypic Leukemia
- Acute Lymphoblastic Leukemia
- Acute Myeloid Leukemia
- Anaplastic Large Cell Lymphoma
- Burkitt Leukemia
- Burkitt Lymphoma
- Chronic Myeloid Leukemia
- Diffuse Large B-Cell Lymphoma
- Follicular Lymphoma
- Hodgkin Lymphoma
- Malignant Solid Tumor
- Mantle Cell Lymphoma
- Marginal Zone Lymphoma
- Multiple Myeloma
- Myelodysplastic Syndromes
- Myelofibrosis
- T-Cell Lymphoblastic Leukemia/Lymphoma
Recruiting Status:
Active, not recruiting
Phase:
Phase 1
Trial Eligibility
Document
Title
- Brief Title: URMC Related Haplo-identical Donor BMT
- Official Title: Haploidentical Donor Hematopoietic Stem Cell Transplantation
Clinical Trial IDs
- ORG STUDY ID: UBMT 15056
- NCT ID: NCT02660281
Conditions
- Hematological Disease
- Immune Deficiencies
- Solid Tumors
- Myelofibrosis
- Multiple Myeloma
- Lymphoma
Interventions
| Drug | Synonyms | Arms |
|---|---|---|
| Fludarabine | Full Intensity Chemo-Only Conditioning | |
| Pre-Stem Cell Infusion Cyclophosphamide | Full Intensity Chemo-Only Conditioning | |
| Pre-Stem Cell Infusion Mesna | Full Intensity Chemo-Only Conditioning | |
| Busulfan | Full Intensity Chemo-Only Conditioning | |
| Melphalan | Reduced Intensity Conditioning | |
| Post-Stem Cell Infusion Cyclophosphamide | Full Intensity Chemo-Only Conditioning | |
| Post-Stem Cell Infusion Mesna | Full Intensity Chemo-Only Conditioning | |
| Thiotepa | Reduced Intensity Conditioning with Addition of Thiotepa |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|---|---|---|
| Full Intensity TBI-based Conditioning | Other | Total Body Irradiation 1200 cGy of 150 cGy over 4 or 5 days, days -5 or -4 to -1 Fludarabine 30 mg/m2/day x 3 days, days -6, -5, -4 Stem Cell Infusion, day 0 Post- Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Mesna 50 mg/kg/day x 2 days, days +3 and +4 |
|
| Full Intensity Chemo-Only Conditioning | Other | Fludarabine 25 mg/m2/day x 5 days, days -6, -5, -4, -3, -2 Busulfan 130 mg/m2/day x 4 days, days -6, -5, -4, -3 Pre-Stem Cell Infusion Cyclophosphamide 14.5 mg/kg/day x 2 days, days -3 and -2 Pre-Stem Cell Infusion Mesna 14.5 mg/kg/day x 2 days, days -3 and -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell Infusion Mesna 50 mg/kg/day x 2 days, days +3 and +4 |
|
| Reduced Intensity Conditioning | Other | Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Melphalan 140 mg/m2/day x 1 day, day -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell InfusionMesna 50 mg/kg/day x 2 days, days +3 and +4 |
|
| Non-Myeloablative Conditioning | Other | Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Pre-Stem Cell Infusion Cyclophosphamide 14.5 mg/kg/day x 2 days, days -3 and -2 Pre-Stem Cell InfusionMesna 14.5 mg/kg/day x 2 days, days -3 and -2 Total Body Irradiation 200 cGy, day -1 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, day +3 and +4 Post-Stem Cell Infusion Mesna 50 mg/kg/day x 2 days, day +3 and +4 |
|
| Reduced Intensity Conditioning with Addition of Thiotepa | Other | Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Thiotepa 8 mg/kg, day -3 Melphalan 140 mg/m2/day x 1 day, day -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell InfusionMesna 50 mg/kg/day x 2 days, days +3 and +4 |
|
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 -
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 6 Months |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| 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. |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | The date of engraftment of ANC is the first of 3 consecutive days of ANC of 500 or higher. The date of engraftment of platelets is the first of 3 consecutive days of platelet counts of 20,000 or higher in the absence of platelet transfusions for at least 7 days prior. |
Secondary Outcome Measures
| Measure: | Percentage of subjects who develop acute graft-versus-host disease. |
| Time Frame: | 100 days following the infusion of stem cells |
| Safety Issue: | |
| Description: | Assess the presence and date of onset of acute GvHD based on the criteria published by Przepiorka et al., Bone Marrow Transplant 1995; 15(6):825-8 as used by the Center for International Blood & Marrow Transplant Research. |
| 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. |
| Time Frame: | 100 days following the infusion of stem cells |
| Safety Issue: | |
| Description: | Assess the severity of acute GvHD based on the criteria published by Przepiorka et al., Bone Marrow Transplant 1995; 15(6):825-8 as used by the Center for International Blood & Marrow Transplant Research. |
| Measure: | Percentage of subjects who develop chronic graft-versus-host disease. |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | Calculate the percentage of patients who develop chronic graft-versus-host disease based on Sullivan KM, Blood 1981; 57:267 as used by the Center for International Blood & Marrow Transplant Research. |
| Measure: | Assess the Maximum Grade: Limited versus Extensive; Maximum Severity: Mild, Moderate or Severe) of chronic GvHD in patients who develop chronic graft-versus- |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | Assess the severity of chronic GvHD in patients who develop chronic graft-versus-host disease based on Sullivan KM, Blood 1981; 57:267 as used by the Center for International Blood & Marrow Transplant Research. |
| Measure: | Disease-free survival |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | Document and update the length of time a subject survives without recurrence of the disease for which they were transplanted minimally at 100 days. 6 months, and yearly following the infusion of stem cells for as long as the patient survives and remains disease-free. |
| Measure: | Time to relapsed disease |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | Document the time to relapse of the disease for which the patient was Minimally assessments will be performed at 100 days. 6 months, and yearly following the infusion of stem cells for as long as the patient survives and remains disease-free. |
| Measure: | Immune reconstitution |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | Evaluate immune reconstitution by measurement of immunoglobulins (IgG, IgA, and IgM), assessment of infections, and lymphocyte analysis |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | University of Rochester |
Last Updated
September 17, 2020
