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Umbilical Cord Blood Transplantation From Unrelated Donors

Primary Purpose

Acute Leukemia, Immune Deficiency Disorder, Congenital Hematological Disorder

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Total Body Irradiation 1200 cGy
Total Body Irradiation 200 cGy
Cyclophosphamide
Mesna
Cord Blood Infusion
Busulfan
Fludarabine
Melphalan
Sponsored by
University of Rochester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Leukemia

Eligibility Criteria

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

Inclusion Criteria:

  • Appropriate diagnosis: Patients must have a disease or syndrome amenable to therapy with hematopoietic stem cell transplantation. Diagnoses include, but are not limited to:
  • 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)
  • Severe aplastic anemia
  • High-Risk Leukemia:
  • 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), and 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, chemo-sensitive, 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
  • Adequate organ function:
  • Cardiac - LVEF >45%, or shortening fraction >25%, Absence of congestive heart failure or conduction disturbances with high risk for sudden death
  • Pulmonary - DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted;
  • Renal - serum Cr < 1.5 times the upper limit of normal for age or GFR ≥ 50 ml/min/1.73m2
  • Hepatic - total bilirubin level < 2 times the upper limit of normal (except for patients with Gilbert's syndrome or hemolysis); if the primary disease process is causal, this criterion will be reconsidered. ALT, AST, and Alkaline phosphatase ≤ 5 times upper limit of normal.
  • Performance Status Karnofsky or Lansky score ≥ 70%.
  • Informed Consent must be obtained prior to initiating conditioning therapy.
  • Receipt of viable cord blood product(s), single or dual, must be confirmed with the stem cell processing laboratory prior to initiating conditioning therapy.

Exclusion Criteria:

  • Availability of 10/10 or 9/10 HLA-matched related or unrelated donor within a reasonable timeframe dictated by the clinical urgency of the transplant
  • Autologous HSCT < 6 months prior to proposed UCB transplant
  • Pregnant or breast feeding
  • Current uncontrolled infection
  • Evidence of HIV infection or positive HIV serology

Sites / Locations

  • Wilmot Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

Other

Arm Label

Full Intensity, TBI-based Conditioning

Full Intensity, Chemo-based Conditioning

Reduced Intensity Chemotherapy

Non-Myeloablative Conditioning

Arm Description

Full Intensity TBI-based Conditioning Total Body Irradiation 1200 cGy in fractions of 150 cGy days -8 or -7 to -4 Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: TBI/Cy

Full Intensity, Chemotherapy Conditioning Busulfan days -7 to -4 Recipients <5 years - 1 mg/kg/dose x 16 doses every 6 hours Recipients >/= 5 years - 0.8 mg/kg/dose x 16 doses every 6 hours Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: Bu/Cy

Reduced Intensity Chemotherapy Fludarabine 30 mg/m2/day x 5 doses days -6 to -2 Melphalan 140 mg/m2/day x 1 dose day -2 Cord Blood Infusion Other names: Flu/Mel

Fludarabine 40 mg/m2/day x 5 doses days -6 to -2 Cyclophosphamide 50 mg/kg/day x 1 dose day -6 Mesna 50 mg/kg/day with 20% loading dose with Cyclophosphamide dose followed by continuous infusion over 24 hours x 1 dose [to be completed 24 hours after Cyclophosphamide dose] Total Body Irradiation 200 cGy in a single fraction day -1 Cord Blood Infusion Other names: Flu/Cy/TBI

Outcomes

Primary Outcome Measures

Engraftment of ANC and Platelets
The date of engraftment of ANC is the first of 3 consecutive days of ANC of 500 or higher based on daily CBC and Differential Counts. The date of engraftment of platelets is the first of three consecutive days of platelet counts of 20,000 or higher in the absence of platelet transfusions for a t least 7 days prior.

Secondary Outcome Measures

Rate of non-engraftment and of secondary graft failure
The percentage of patients who fail to initially engraft ANC will be tabulated as well as the percentage of patients who have primary engraftment of ANC but whose graft fails as evidenced by pancytopenia, failure of bone marrow function and loss of donor chimerism following initial engraftment of ANC.
Incidence of acute graft-versus-host disease
Routine physical exams, liver function tests, and clinical history of diarrhea and upper GI symptoms will be used to assess the presence of, the maximum severity of and the date of onset of Acute GvHD based on the criteria published by Przepioka et al., Bone Marrow Transplant 1995; 15(6):825-8 as used by the Center for International Blood & Marrow Transplant Research. The percentage of patients developing symptoms of acute graft-versus-host disease will be tabulated.
Incidence of chronic graft-versus-host disease
Assess the presence of and the maximum severity of and the date of onset of chronic GvHD based on Sullivan KM, Blood 1981;57-267 as used by the Cneter 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 at 30 days, 100 days, 6 months and yearly following the infusion of cord blood stem cells for as long as the subjects survive and remain disease-free.

Full Information

First Posted
December 26, 2016
Last Updated
July 17, 2023
Sponsor
University of Rochester
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1. Study Identification

Unique Protocol Identification Number
NCT03016806
Brief Title
Umbilical Cord Blood Transplantation From Unrelated Donors
Official Title
Umbilical Cord Blood Transplantation From Unrelated Donors
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 2015 (undefined)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
June 2026 (Anticipated)

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 is a single-center, treatment protocol with 4 possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution.
Detailed Description
This study is a single-center treatment protocol with four possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution. Enrolled patients will receive chemotherapy +/-total body radiation as a pre-transplant conditioning regimen. Patients will then receive cord blood stem cells followed by GvHD prophylaxis that will include Tacrolimus and Mycophenolate Mofetil, or Cyclosporin A and Methylprednisolone. 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
Acute Leukemia, Immune Deficiency Disorder, Congenital Hematological Disorder, Metabolism Disorder, Aplastic Anemia, Myelodysplastic Syndromes, Chronic Leukemia, Lymphoma, Multiple Myeloma, Solid Tumor

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Full Intensity, TBI-based Conditioning
Arm Type
Other
Arm Description
Full Intensity TBI-based Conditioning Total Body Irradiation 1200 cGy in fractions of 150 cGy days -8 or -7 to -4 Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: TBI/Cy
Arm Title
Full Intensity, Chemo-based Conditioning
Arm Type
Other
Arm Description
Full Intensity, Chemotherapy Conditioning Busulfan days -7 to -4 Recipients <5 years - 1 mg/kg/dose x 16 doses every 6 hours Recipients >/= 5 years - 0.8 mg/kg/dose x 16 doses every 6 hours Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: Bu/Cy
Arm Title
Reduced Intensity Chemotherapy
Arm Type
Other
Arm Description
Reduced Intensity Chemotherapy Fludarabine 30 mg/m2/day x 5 doses days -6 to -2 Melphalan 140 mg/m2/day x 1 dose day -2 Cord Blood Infusion Other names: Flu/Mel
Arm Title
Non-Myeloablative Conditioning
Arm Type
Other
Arm Description
Fludarabine 40 mg/m2/day x 5 doses days -6 to -2 Cyclophosphamide 50 mg/kg/day x 1 dose day -6 Mesna 50 mg/kg/day with 20% loading dose with Cyclophosphamide dose followed by continuous infusion over 24 hours x 1 dose [to be completed 24 hours after Cyclophosphamide dose] Total Body Irradiation 200 cGy in a single fraction day -1 Cord Blood Infusion Other names: Flu/Cy/TBI
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation 1200 cGy
Other Intervention Name(s)
TBI 1200 cGy
Intervention Description
Total Body Irradiation 1200 cGy in 8 fractions
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation 200 cGy
Other Intervention Name(s)
TBI 200 cGy
Intervention Description
Total Body Irradiation 200 cGy in one fraction
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cy
Intervention Description
50 mg/kg or 60 mg/kg
Intervention Type
Drug
Intervention Name(s)
Mesna
Other Intervention Name(s)
Pre-Mesna
Intervention Description
50 mg/kg or 60 mg/kg plus 10% loading dose
Intervention Type
Procedure
Intervention Name(s)
Cord Blood Infusion
Intervention Description
Intravenous infusion of cord blood stem cells
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Bu
Intervention Description
0.8 mg/kg x 16 doses
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Flu
Intervention Description
30 mg/m2/day x 5 or 40 mg/m2/day x 5
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Mel
Intervention Description
140 mg/m2
Primary Outcome Measure Information:
Title
Engraftment of ANC and Platelets
Description
The date of engraftment of ANC is the first of 3 consecutive days of ANC of 500 or higher based on daily CBC and Differential Counts. The date of engraftment of platelets is the first of three consecutive days of platelet counts of 20,000 or higher in the absence of platelet transfusions for a t 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.]
Secondary Outcome Measure Information:
Title
Rate of non-engraftment and of secondary graft failure
Description
The percentage of patients who fail to initially engraft ANC will be tabulated as well as the percentage of patients who have primary engraftment of ANC but whose graft fails as evidenced by pancytopenia, failure of bone marrow function and loss of donor chimerism following initial engraftment of ANC.
Time Frame
At 30 days, 100 days, 6 months and yearly from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.
Title
Incidence of acute graft-versus-host disease
Description
Routine physical exams, liver function tests, and clinical history of diarrhea and upper GI symptoms will be used to assess the presence of, the maximum severity of and the date of onset of Acute GvHD based on the criteria published by Przepioka et al., Bone Marrow Transplant 1995; 15(6):825-8 as used by the Center for International Blood & Marrow Transplant Research. The percentage of patients developing symptoms of acute graft-versus-host disease will be tabulated.
Time Frame
At 30 days and 100 days after transplant from the date of transplant until the date of documented acute GvHD.
Title
Incidence of chronic graft-versus-host disease
Description
Assess the presence of and the maximum severity of and the date of onset of chronic GvHD based on Sullivan KM, Blood 1981;57-267 as used by the Cneter for International Blood & Marrow Transplant Research.
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 death 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 at 30 days, 100 days, 6 months and yearly following the infusion of cord blood stem cells for as long as the subjects survive and remain disease-free.
Time Frame
At 30 days, 100 days, 6 months and yearly after transplant from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Months
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Appropriate diagnosis: Patients must have a disease or syndrome amenable to therapy with hematopoietic stem cell transplantation. Diagnoses include, but are not limited to: 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) Severe aplastic anemia High-Risk Leukemia: 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), and 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, chemo-sensitive, 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 Adequate organ function: Cardiac - LVEF >45%, or shortening fraction >25%, Absence of congestive heart failure or conduction disturbances with high risk for sudden death Pulmonary - DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted; Renal - serum Cr < 1.5 times the upper limit of normal for age or GFR ≥ 50 ml/min/1.73m2 Hepatic - total bilirubin level < 2 times the upper limit of normal (except for patients with Gilbert's syndrome or hemolysis); if the primary disease process is causal, this criterion will be reconsidered. ALT, AST, and Alkaline phosphatase ≤ 5 times upper limit of normal. Performance Status Karnofsky or Lansky score ≥ 70%. Informed Consent must be obtained prior to initiating conditioning therapy. Receipt of viable cord blood product(s), single or dual, must be confirmed with the stem cell processing laboratory prior to initiating conditioning therapy. Exclusion Criteria: Availability of 10/10 or 9/10 HLA-matched related or unrelated donor within a reasonable timeframe dictated by the clinical urgency of the transplant Autologous HSCT < 6 months prior to proposed UCB transplant Pregnant or breast feeding Current uncontrolled infection Evidence of HIV infection or positive HIV serology
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jane L Liesveld, MD
Phone
585-275-4099
Email
jane_liesveld@urmc.rochester.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Michael W Becker, MD
Phone
585-275-4099
Email
michael_becker@urmc.rochester.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jane L Liesveld, MD
Organizational Affiliation
Medical Director, Blood & Marrow Transplant Unit
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
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jane L Liesveld, MD
Phone
585-275-4099
Email
jane_liesveld@urmc.rochester.edu
First Name & Middle Initial & Last Name & Degree
Michael W Becker, MD
Phone
585-275-4099
Email
michael_becker@urmc.rochester.edu

12. IPD Sharing Statement

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Umbilical Cord Blood Transplantation From Unrelated Donors

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