Umbilical Cord Blood Transplantation From Unrelated Donors

• ClinicalTrials.gov Identifier: NCT03016806
• Recruitment Status: Recruiting
• First Posted: January 11, 2017
• Last Update Posted: June 22, 2022
• Sponsor: University of Rochester
• Information provided by (Responsible Party): Jane Liesveld, University of Rochester

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.

Condition or disease	Intervention/treatment	Phase
Acute Leukemia; Immune Deficiency Disorder; Congenital Hematological Disorder; Metabolism Disorder; Aplastic Anemia; Myelodysplastic Syndromes; Chronic Leukemia; Lymphoma; Multiple Myeloma; Solid Tumor	Radiation: Total Body Irradiation 1200 cGy; Radiation: Total Body Irradiation 200 cGy; Drug: Cyclophosphamide; Drug: Mesna; Procedure: Cord Blood Infusion; Drug: Busulfan; Drug: Fludarabine; Drug: Melphalan	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Umbilical Cord Blood Transplantation From Unrelated Donors
• Study Start Date: June 2015
• Estimated Primary Completion Date: June 2025
• Estimated Study Completion Date: June 2026

Arms and Interventions

Arm	Intervention/treatment
Full Intensity, TBI-based Conditioning; 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	Radiation: Total Body Irradiation 1200 cGy; Total Body Irradiation 1200 cGy in 8 fractions; Other Name: TBI 1200 cGy; Drug: Cyclophosphamide; 50 mg/kg or 60 mg/kg; Other Name: Cy; Drug: Mesna; 50 mg/kg or 60 mg/kg plus 10% loading dose; Other Name: Pre-Mesna; Procedure: Cord Blood Infusion; Intravenous infusion of cord blood stem cells
Full Intensity, Chemo-based Conditioning; 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	Drug: Cyclophosphamide; 50 mg/kg or 60 mg/kg; Other Name: Cy; Drug: Mesna; 50 mg/kg or 60 mg/kg plus 10% loading dose; Other Name: Pre-Mesna; Procedure: Cord Blood Infusion; Intravenous infusion of cord blood stem cells; Drug: Busulfan; 0.8 mg/kg x 16 doses; Other Name: Bu
Reduced Intensity Chemotherapy; 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	Procedure: Cord Blood Infusion; Intravenous infusion of cord blood stem cells; Drug: Fludarabine; 30 mg/m2/day x 5 or 40 mg/m2/day x 5; Other Name: Flu; Drug: Melphalan; 140 mg/m2; Other Name: Mel
Non-Myeloablative Conditioning; 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	Radiation: Total Body Irradiation 200 cGy; Total Body Irradiation 200 cGy in one fraction; Other Name: TBI 200 cGy; Drug: Cyclophosphamide; 50 mg/kg or 60 mg/kg; Other Name: Cy; Drug: Mesna; 50 mg/kg or 60 mg/kg plus 10% loading dose; Other Name: Pre-Mesna; Drug: Fludarabine; 30 mg/m2/day x 5 or 40 mg/m2/day x 5; Other Name: Flu

Outcome Measures

Primary Outcome Measures :

1. Engraftment of ANC and Platelets [ 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 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 :

1. Rate of non-engraftment and of secondary graft failure [ 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. ]
   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.
2. Incidence of acute graft-versus-host disease [ Time Frame: 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.
3. Incidence of chronic graft-versus-host disease [ 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. ]
   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.
4. Disease-free survival [ 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. ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 2 Months to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Jane L Liesveld, MD; 585-275-4099; jane_liesveld@urmc.rochester.edu

Contact: Michael W Becker, MD; 585-275-4099; michael_becker@urmc.rochester.edu

Locations

United States, New York

Wilmot Cancer Institute; Recruiting

Rochester, New York, United States, 14642

Contact: Jane L Liesveld, MD 585-275-4099 jane_liesveld@urmc.rochester.edu

Contact: Michael W Becker, MD 585-275-4099 michael_becker@urmc.rochester.edu

Sponsors and Collaborators

University of Rochester

Investigators

• Principal Investigator: Jane L Liesveld, MD; Medical Director, Blood & Marrow Transplant Unit

More Information

• Responsible Party: Jane Liesveld, Clinical Director, BMT Unit, University of Rochester
• ClinicalTrials.gov Identifier: NCT03016806
• Other Study ID Numbers: UBMT 15029
• First Posted: January 11, 2017
• Last Update Posted: June 22, 2022
• Last Verified: June 2022

Additional relevant MeSH terms:

Leukemia; Multiple Myeloma; Myelodysplastic Syndromes; Anemia, Aplastic; Hematologic Diseases; Immunologic Deficiency Syndromes; Disease; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Anemia; Bone Marrow Failure Disorders; Cyclophosphamide; Melphalan; Busulfan; Fludarabine; Mesna; Immunosuppressive Agents; Immunologic Factors