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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01962636
• Other study ID #: 2013OC013
• Status: Recruiting
• Phase: N/A
• Start date: December 2016
• Est. completion date: October 2025

Study information

• Verified date: November 2023
• Source: Masonic Cancer Center, University of Minnesota
• Contact: Claudio Brunstein, MD
• Phone: 612-625-3918
• Email: bruns072[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: October 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 55 Years

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia (ALL)
• Acute Myeloid Leukemia (AML)
• Burkitt Lymphoma
• Burkitt's Lymphoma
• Chronic Lymphocytic Leukemia
• Chronic Myelogenous Leukemia
• Diffuse Large B Cell Lymphoma
• Follicular Lymphoma
• Hematologic Diseases
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Plasma Cell
• Leukemia, Prolymphocytic
• Lymphoblastic Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Lymphoplasmacytic Lymphoma
• Mantle-Cell Lymphoma
• Marginal Zone B-Cell Lymphoma
• Multiple Myeloma
• Myelodysplasia
• Myelodysplastic Syndromes
• Myelofibrosis
• Non-Hodgkin Lymphoma
• Plasma Cell Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Primary Myelofibrosis
• Prolymphocytic Leukemia
• Small Lymphocytic Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Drug:
• Fludarabine
25 mg/m^2 IV of Fludarabine will be given over 1 hour on days -8, -7, and -6 pre-UCB transplant.
• Cyclophosphamide
60 mg/kg IV of Cyclophosphamide will be given over 2 hours on days -7 and -6 pre-UCB transplant.

Radiation:
• Total Body Irradiation
165 cGy of total body irradiation will be given twice a day on days -4, -3, -2, and -1.

Drug:
• Cyclosporine A
Cyclosporine A (CSA) will start day -3 and will be administered PO/IV maintaining a trough level between 200 and 400 ng/mL. For adults the initial dose will be 2.5 mg/kg IV over 1 hour every 12 hours. For children < 40 kg the initial dose will be 2.5 mg/kg IV over 1 hour every 8 hours.
• Mycophenylate mofetil
Mycophenylate mofetil (MMF) 3 gram/day IV/PO for patients who are = 40 kg divided in 2 or 3 doses. Pediatric patient (<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning day -3.

Biological:
• Umbilical cord blood
Pre-medications and UCB infusion will be per current institutional policies/guidelines. The infusion of the first UCB unit should begin within 15 minutes, and no later than 30 minutes after arrival on the Unit. If 2 units are used, both cords will be infused within 30-60 minutes of each other as deemed clinically safe by the BMT attending or designee.

Locations

Country	Name	City	State
United States	University of Minnesota Masonic Cancer Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival at 1 year post-transplant	The number of patients that are still living 1 year after UCBT.	1 year
Secondary	Incidence of neutrophil engraftment at day 42.	Number of subjects with neutrophil engraftment at day 42 post UCBT.	42 days
Secondary	Platelet engraftment at 1 year.	Number of patients with platelet engraftment at 1 year post UCBT.	1 year
Secondary	Pattern of chimerism after transplant.	Pattern of chimerism after transplant. Chimerism will be plotted with box-plots and described over time.	1 year
Secondary	Incidence of graft failure.	Cumulative incidence of graft failure after UCBT.	100 days
Secondary	Incidence of acute graft versus host disease at 100 days.	Cumulative incidence will be used to estimate acute graft versus host disease 100 days after UCBT.	100 days
Secondary	Incidence of chronic graft versus host disease at 1 year.	Cumulative incidence will be used to estimate chronic GVHD at 1 year post UCBT.	1 year
Secondary	Incidence of transplant related mortality at 6 months.	Cumulative incidence will be used to estimate transplant related mortality at 6 months post UCBT.	6 months
Secondary	Incidence of disease free survival	Kaplan-Meier curves will be used to estimate disease-free survival at 1 and 2 years post UCBT.	1, 2 years
Secondary	Incidence of overall survival.	Kaplan-Meier curves will be used to estimate overall survival at 1 and 2 years post UCBT.	1, 2 years