Umbilical Cord Blood Transplantation From Unrelated Donors

Phase 1

Recruiting

• Conditions: Metabolism Disorder; Lymphoma; Aplastic Anemia; Acute Leukemia; Myelodysplastic Syndromes; Congenital Hematological Disorder; Chronic Leukemia; Multiple Myeloma; Immune Deficiency Disorder; Solid Tumor
• Interventions: Procedure: Cord Blood Infusion; Radiation: Total Body Irradiation 200 cGy; Radiation: Total Body Irradiation 1200 cGy; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Mesna; Drug: Melphalan; Drug: Busulfan

• Registration Number: NCT03016806
• Lead Sponsor: University of Rochester

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.

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2016-12-26
• Study First Submitted QC: 2017-01-07
• Study First Posted: 2017-01-11
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-15
• Last Update Posted: 2024-08-19
• Primary Completion: 2025-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Reduced Intensity Chemotherapy	Cord Blood Infusion	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
Reduced Intensity Chemotherapy	Fludarabine	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
Full Intensity, TBI-based Conditioning	Cord Blood Infusion	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, Chemo-based Conditioning	Cord Blood Infusion	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
Non-Myeloablative Conditioning	Total Body Irradiation 200 cGy	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
Full Intensity, TBI-based Conditioning	Total Body Irradiation 1200 cGy	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, TBI-based Conditioning	Cyclophosphamide	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, TBI-based Conditioning	Mesna	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, Chemo-based Conditioning	Mesna	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
Full Intensity, Chemo-based Conditioning	Cyclophosphamide	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
Full Intensity, Chemo-based Conditioning	Busulfan	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	Melphalan	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
Non-Myeloablative Conditioning	Cyclophosphamide	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
Non-Myeloablative Conditioning	Mesna	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
Non-Myeloablative Conditioning	Fludarabine	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

Primary Outcome Measures

Name	Time	Method
Engraftment of ANC and Platelets	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 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

Name	Time	Method
Incidence of acute graft-versus-host disease	At 30 days and 100 days after transplant from the date of transplant until the date of documented acute GvHD.	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	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.	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.
Rate of non-engraftment and of secondary graft failure	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.	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.
Disease-free survival	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.	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.

Trial Locations

Locations (1)

Wilmot Cancer Institute; 🇺🇸 Rochester, New York, United States