- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02660281
URMC Related Haplo-identical Donor BMT (HaploOnly)
Haploidentical Donor Hematopoietic Stem Cell Transplantation
Study Overview
Status
Conditions
Intervention / Treatment
- Drug: Fludarabine
- Drug: Melphalan
- Radiation: Total Body Irradiation 1200 cGy
- Procedure: Stem Cell Infusion
- Drug: Post-Stem Cell Infusion Cyclophosphamide
- Drug: Post-Stem Cell Infusion Mesna
- Drug: Pre-Stem Cell Infusion Cyclophosphamide
- Drug: Pre-Stem Cell Infusion Mesna
- Drug: Busulfan
- Drug: Thiotepa
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
-
Rochester, New York, United States, 14642
- Wilmot Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 -
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Full Intensity TBI-based Conditioning
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
1200 cGy TBI in 8 fractions
Other Names:
Stem cell infusion
Cyclophosphamide given after the stem cell infusion
Mesna given after the Stem Cell Infusion
|
Other: Full Intensity Chemo-Only Conditioning
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
Stem cell infusion
Cyclophosphamide given after the stem cell infusion
Mesna given after the Stem Cell Infusion
Cyclophosphamide given prior to the stem cell infusion
Mesna given prior to the stem cell infusion
Busulfan
|
Other: Reduced Intensity Conditioning
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
Melphalan
Stem cell infusion
Cyclophosphamide given after the stem cell infusion
Mesna given after the Stem Cell Infusion
|
Other: Non-Myeloablative Conditioning
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
1200 cGy TBI in 8 fractions
Other Names:
Stem cell infusion
Cyclophosphamide given after the stem cell infusion
Mesna given after the Stem Cell Infusion
Cyclophosphamide given prior to the stem cell infusion
Mesna given prior to the stem cell infusion
|
Other: Reduced Intensity Conditioning with Addition of Thiotepa
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
|
Fludarabine
Melphalan
Stem cell infusion
Cyclophosphamide given after the stem cell infusion
Mesna given after the Stem Cell Infusion
Thiotepa
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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.
|
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.
|
Rate of non-engraftment and secondary graft failure
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.
|
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.
|
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 Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of subjects who develop acute graft-versus-host disease.
Time Frame: 100 days following the infusion of stem cells
|
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.
|
100 days following the infusion of stem cells
|
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
|
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.
|
100 days following the infusion of stem cells
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
Evaluate immune reconstitution by measurement of immunoglobulins (IgG, IgA, and IgM), assessment of infections, and lymphocyte analysis
|
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.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jeffrey Andolina, MD, Wilmot Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Multiple Myeloma
- Hematologic Diseases
- Immunologic Deficiency Syndromes
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Melphalan
- Fludarabine
- Thiotepa
- Busulfan
- Mesna
Other Study ID Numbers
- UBMT 15056
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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