URMC Related Haplo-identical Donor BMT

Multiple Myeloma Clinical Trial

— HaploOnly  

Official title:

Haploidentical Donor Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02660281
• Other study ID #: UBMT 15056
• Status: Completed
• Phase: Phase 1
• Start date: October 2015
• Est. completion date: January 7, 2021

Study information

• Verified date: November 2021
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: January 7, 2021
• Est. primary completion date: October 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 75 Years

Eligibility

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 -

Related Conditions & MeSH terms

• Hematologic Diseases
• Hematological Disease
• Immune Deficiencies
• Immunologic Deficiency Syndromes
• Lymphoma
• Multiple Myeloma
• Myelofibrosis
• Solid Tumors

Intervention

Radiation:
• Total Body Irradiation 1200 cGy
1200 cGy TBI in 8 fractions

Drug:
• Fludarabine
Fludarabine
• Pre-Stem Cell Infusion Cyclophosphamide
Cyclophosphamide given prior to the stem cell infusion
• Pre-Stem Cell Infusion Mesna
Mesna given prior to the stem cell infusion
• Busulfan
Busulfan
• Melphalan
Melphalan

Procedure:
• Stem Cell Infusion
Stem cell infusion

Drug:
• Post-Stem Cell Infusion Cyclophosphamide
Cyclophosphamide given after the stem cell infusion
• Post-Stem Cell Infusion Mesna
Mesna given after the Stem Cell Infusion
• Thiotepa
Thiotepa

Locations

Country	Name	City	State
United States	Wilmot Cancer Institute	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
University of Rochester

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.
Primary	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.	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	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.	100 days following the infusion of stem cells
Secondary	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.	100 days following the infusion of stem cells
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	Immune reconstitution	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.