Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases

Not Applicable

Recruiting

• Conditions: Acute Myeloid Leukemia (AML); Acute Lymphocytic Leukemia (ALL); Myelodysplasia; Chronic Lymphocytic Leukemia; Marginal Zone B-Cell Lymphoma; Follicular Lymphoma; Non-Hodgkin Lymphoma; Multiple Myeloma; Chronic Myelogenous Leukemia; Plasma Cell Leukemia
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Irradiation; Drug: Cyclosporine A; Drug: Mycophenylate mofetil; Biological: Umbilical cord blood

• Registration Number: NCT01962636
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary

This is a treatment guideline for an unrelated umbilical cord blood transplant (UCBT) using a myeloablative preparative regimen for the treatment of hematological diseases, including, but not limited to acute leukemias. The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI).

Detailed Description

This is a study to collect routine clinical data from UCBT using unrelated single or double UCB units as an alternative, non-HLA-matched stem cell source for patients with hematological diseases.

* data collection from transplant preparative therapy consisting of treatments with chemotherapeutic regimens and total body irradiation.

* data collection from umbilical cord blood selection and infusion.

* data collection from standard supportive disease and transplant related care.

Pre- and post-transplant medication, UCB selection and infusion, supportive care, and follow-up will be according to the current University of Minnesota BMT guidelines.

An average of 18 patients are expected to be treated on this protocol per year.

Study Timeline

• Study First Submitted: 2013-10-10
• Study First Submitted QC: 2013-10-10
• Study First Posted: 2013-10-14
• Study Start: 2016-12
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-01
• Last Update Posted: 2024-11-04
• Primary Completion: 2025-10
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Eligible Disease Status

  • Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
  • Very high risk pediatric patients with AML: Patients <21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy.
  • Acute Lymphocytic Leukemia (ALL): high risk CR1 as defined by cytogenetics (such as t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
  • Very high risk pediatric patients with ALL: patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
  • Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
  • Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
  • Advanced Myelofibrosis
  • Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia or high risk cytogenetics: Blasts must be < 10% by a representative bone marrow aspirate morphology.
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for de-bulking chemotherapy before transplant.
  • Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible after initial therapy in CR1+ or PR1+.
  • Large Cell NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
  • Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
  • Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
  • Myeloproliferative Syndromes

• Availability of suitable UCB unit(s)

• 0 to 55 years

• Voluntary written consent (adult or parental/guardian)

Exclusion Criteria

• previous irradiation that precludes the safe administration of TBI - Radiation Oncology will evaluate all patients who have had previous radiation therapy
• chemotherapy refractory large cell and high grade NHL (ie progressive disease after > 2 salvage regimens)
• if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18 years old prior myeloablative allotransplant or autologous transplant
• extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation
• pregnant or breastfeeding
• HIV positive

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Umbilical Cord Blood Transplant	Total Body Irradiation	The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI)followed by umbilical cord blood transplant. Immunosuppressive Cyclosporine and Mycophenylate Mofetil (MMF) will be administered pre- and post UCBT.
Umbilical Cord Blood Transplant	Cyclosporine A	The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI)followed by umbilical cord blood transplant. Immunosuppressive Cyclosporine and Mycophenylate Mofetil (MMF) will be administered pre- and post UCBT.
Umbilical Cord Blood Transplant	Mycophenylate mofetil	The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI)followed by umbilical cord blood transplant. Immunosuppressive Cyclosporine and Mycophenylate Mofetil (MMF) will be administered pre- and post UCBT.
Umbilical Cord Blood Transplant	Umbilical cord blood	The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI)followed by umbilical cord blood transplant. Immunosuppressive Cyclosporine and Mycophenylate Mofetil (MMF) will be administered pre- and post UCBT.
Umbilical Cord Blood Transplant	Fludarabine	The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI)followed by umbilical cord blood transplant. Immunosuppressive Cyclosporine and Mycophenylate Mofetil (MMF) will be administered pre- and post UCBT.
Umbilical Cord Blood Transplant	Cyclophosphamide	The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI)followed by umbilical cord blood transplant. Immunosuppressive Cyclosporine and Mycophenylate Mofetil (MMF) will be administered pre- and post UCBT.

Primary Outcome Measures

Name	Time	Method
Survival at 1 year post-transplant	1 year	The number of patients that are still living 1 year after UCBT.

Secondary Outcome Measures

Name	Time	Method
Incidence of acute graft versus host disease at 100 days.	100 days	Cumulative incidence will be used to estimate acute graft versus host disease 100 days after UCBT.
Incidence of chronic graft versus host disease at 1 year.	1 year	Cumulative incidence will be used to estimate chronic GVHD at 1 year post UCBT.
Incidence of neutrophil engraftment at day 42.	42 days	Number of subjects with neutrophil engraftment at day 42 post UCBT.
Incidence of graft failure.	100 days	Cumulative incidence of graft failure after UCBT.
Incidence of overall survival.	1, 2 years	Kaplan-Meier curves will be used to estimate overall survival at 1 and 2 years post UCBT.
Platelet engraftment at 1 year.	1 year	Number of patients with platelet engraftment at 1 year post UCBT.
Pattern of chimerism after transplant.	1 year	Pattern of chimerism after transplant. Chimerism will be plotted with box-plots and described over time.
Incidence of transplant related mortality at 6 months.	6 months	Cumulative incidence will be used to estimate transplant related mortality at 6 months post UCBT.
Incidence of disease free survival	1, 2 years	Kaplan-Meier curves will be used to estimate disease-free survival at 1 and 2 years post UCBT.

Trial Locations

Locations (1)

University of Minnesota Masonic Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States