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URMC Related Haplo-identical Donor BMT (HaploOnly)

Primary Purpose

Hematological Disease, Immune Deficiencies, Solid Tumors

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Total Body Irradiation 1200 cGy
Fludarabine
Pre-Stem Cell Infusion Cyclophosphamide
Pre-Stem Cell Infusion Mesna
Busulfan
Melphalan
Stem Cell Infusion
Post-Stem Cell Infusion Cyclophosphamide
Post-Stem Cell Infusion Mesna
Thiotepa
Sponsored by
University of Rochester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematological Disease

Eligibility Criteria

6 Months - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 -

Sites / Locations

  • Wilmot Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Other

Other

Other

Other

Other

Arm Label

Full Intensity TBI-based Conditioning

Full Intensity Chemo-Only Conditioning

Reduced Intensity Conditioning

Non-Myeloablative Conditioning

Reduced Intensity Conditioning with Addition of Thiotepa

Arm Description

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.
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.
Rate of non-engraftment and secondary graft failure
The percentage of patients who fail to engraft ANC will be tabulated as well as the percentage of patients who have primary engraftment of ANC but whose graft then fails as evidenced by pancytopenia and failure of bone marrow function.

Secondary Outcome Measures

Percentage of subjects who develop acute graft-versus-host disease.
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.
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.
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.
Percentage of subjects who develop chronic graft-versus-host disease.
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.
Assess the Maximum Grade: Limited versus Extensive; Maximum Severity: Mild, Moderate or Severe) of chronic GvHD in patients who develop chronic graft-versus-
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.
Disease-free survival
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.
Time to relapsed disease
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.
Immune reconstitution
Evaluate immune reconstitution by measurement of immunoglobulins (IgG, IgA, and IgM), assessment of infections, and lymphocyte analysis

Full Information

First Posted
November 24, 2015
Last Updated
November 1, 2021
Sponsor
University of Rochester
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1. Study Identification

Unique Protocol Identification Number
NCT02660281
Brief Title
URMC Related Haplo-identical Donor BMT
Acronym
HaploOnly
Official Title
Haploidentical Donor Hematopoietic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
October 2015 (undefined)
Primary Completion Date
October 28, 2019 (Actual)
Study Completion Date
January 7, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Rochester

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematological Disease, Immune Deficiencies, Solid Tumors, Myelofibrosis, Multiple Myeloma, Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Full Intensity TBI-based Conditioning
Arm Type
Other
Arm Description
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
Arm Title
Full Intensity Chemo-Only Conditioning
Arm Type
Other
Arm Description
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
Arm Title
Reduced Intensity Conditioning
Arm Type
Other
Arm Description
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
Arm Title
Non-Myeloablative Conditioning
Arm Type
Other
Arm Description
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
Arm Title
Reduced Intensity Conditioning with Addition of Thiotepa
Arm Type
Other
Arm Description
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
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation 1200 cGy
Other Intervention Name(s)
TBI
Intervention Description
1200 cGy TBI in 8 fractions
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine
Intervention Type
Drug
Intervention Name(s)
Pre-Stem Cell Infusion Cyclophosphamide
Intervention Description
Cyclophosphamide given prior to the stem cell infusion
Intervention Type
Drug
Intervention Name(s)
Pre-Stem Cell Infusion Mesna
Intervention Description
Mesna given prior to the stem cell infusion
Intervention Type
Drug
Intervention Name(s)
Busulfan
Intervention Description
Busulfan
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
Melphalan
Intervention Type
Procedure
Intervention Name(s)
Stem Cell Infusion
Intervention Description
Stem cell infusion
Intervention Type
Drug
Intervention Name(s)
Post-Stem Cell Infusion Cyclophosphamide
Intervention Description
Cyclophosphamide given after the stem cell infusion
Intervention Type
Drug
Intervention Name(s)
Post-Stem Cell Infusion Mesna
Intervention Description
Mesna given after the Stem Cell Infusion
Intervention Type
Drug
Intervention Name(s)
Thiotepa
Intervention Description
Thiotepa
Primary Outcome Measure Information:
Title
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.
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.
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.
Title
Rate of non-engraftment and secondary graft failure
Description
The percentage of patients who fail to engraft ANC will be tabulated as well as the percentage of patients who have primary engraftment of ANC but whose graft then fails as evidenced by pancytopenia and failure of bone marrow function.
Time Frame
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 Outcome Measure Information:
Title
Percentage of subjects who develop acute graft-versus-host disease.
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.
Time Frame
100 days following the infusion of stem cells
Title
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.
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.
Time Frame
100 days following the infusion of stem cells
Title
Percentage of subjects who develop chronic graft-versus-host disease.
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.
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.
Title
Assess the Maximum Grade: Limited versus Extensive; Maximum Severity: Mild, Moderate or Severe) of chronic GvHD in patients who develop chronic graft-versus-
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.
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.
Title
Disease-free survival
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.
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.
Title
Time to relapsed disease
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.
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.
Title
Immune reconstitution
Description
Evaluate immune reconstitution by measurement of immunoglobulins (IgG, IgA, and IgM), assessment of infections, and lymphocyte analysis
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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: Patient Age below 6 months or over 75 years Availability of a 10/10 HLA-matched related or unrelated donor within a reasonable time-frame dictated by the clinical urgency of the transplant Autologous HSCT < 6 months prior to proposed haplo-SCT Pregnant or breast-feeding Current uncontrolled infection Evidence of HIV infection or positive HIV serology Anti-donor HLA antibodies with positive crossmatch and unsuccessful -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Andolina, MD
Organizational Affiliation
Wilmot Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wilmot Cancer Institute
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States

12. IPD Sharing Statement

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URMC Related Haplo-identical Donor BMT

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