Intra-Osseous Co-Transplant of UCB and hMSC

NCT02181478 | Completed Early Phase 1 FDA Drug

• 3 other identifiers: CASE1Z14NCI-2014-01316P30CA043703
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial studies intra-osseous donor umbilical cord blood and mesenchymal stromal cell co-transplant in treating patients with hematologic malignancies. Giving low doses of chemotherapy and total-body irradiation before a co-transplant of donor umbilical cord blood and mesenchymal stromal cells into the bone (intra-osseous) helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil at the time of transplant may stop this from happening.

Conditions

Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndromes; Myelofibrosis; Relapsed Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Relapsed Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Lymphoid Malignancies; Chronic Myelogenous Leukemia

Keywords

Total Body Irradiation; Human Mesenchymal Stromal Cells; hMSC; Cyclophosphamide; Fludarabine; Dimethyl Sulfoxide; DMSO; Cyclosporine; Mycophenolate Mofetil; MMF; Granulocyte- Colony Stimulating Factor; G-CSF; GVHD; Cancer; feasibility

Outcome Measures

Primary Outcomes (4)

• Number of patients with BM cellularity failure: Measure of feasibility

  Primary graft failure is defined by \<10% BM cellularity in bone marrow biopsies. Failure in more than 30% of patients will indicate unfeasibility of treatment

  42 days after transplant

• Number of patients with ANC failure without evidence of disease: Measure of feasibility

  Primary graft failure is defined by \<500 ANC cell/ul in bone marrow biopsies. Failure in more than 30% of patients will indicate unfeasibility of treatment

  42 days after transplant

• Number of patients with hematopoietic recovery without evidence of donor umbilical cord blood engraftment: Measure of feasibility

  Primary graft failure is defined by hematopoietic recovery with \<10% donor cell chimerism. Failure in more than 30% of patients will indicate unfeasibility of treatment

  42 days after transplant

• Number of patients with hematopoietic recovery without evidence of donor umbilical cord blood engraftment: Measure of feasibility

  Primary graft failure is defined by hematopoietic recovery with \<40% donor cell chimerism. Failure in more than 30% of patients will indicate unfeasibility of treatment

  100 days after transplant

Secondary Outcomes (5)

• Incidence of toxicities assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 12 months

• Rate of neutrophil recovery

  Up to 12 months

• Rate of platelet recovery

  Up to 12 months

• Median time of neutrophil recovery

  Up to 12 months

• Median time of platelet recovery

  Up to 12 months

Study Arms (1)

Treatment (intra-osseous UCB with hMSC co-transplant)

EXPERIMENTAL

REDUCED INTENSITY CONDITIONING (RIC): Flu/Cy/TBI: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total-body irradiation on day -1. Flu/Mel: Patients receive fludarabine daily on days -5 to -2, a single dose of melphalan on day -2, and ATG on day -3 and day-2. GVHD PROPHYLAXIS: Patients receive cyclosporine PO or IV over 2 hours every 12 hours on beginning on days -5 to 100 with taper beginning on day 100 and mycophenolate mofetil IV or PO BID on days -5 to 100. TRANSPLANT: Patients undergo a co-transplantation of an intra-osseous umbilical cord blood transplantation and a mesenchymal stem cell transplantation on day 0.

Drug: cyclophosphamide; Drug: fludarabine phosphate; Radiation: total-body irradiation; Drug: cyclosporine; Drug: mycophenolate mofetil; Procedure: umbilical cord blood transplantation; Procedure: mesenchymal stem cell transplantation

Interventions

cyclophosphamide DRUG

All patients will receive a single IV dose of 50 mg/kg of cyclophosphamide on day -6

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (intra-osseous UCB with hMSC co-transplant)

fludarabine phosphate DRUG

Given by IV during prep at 40mg/m2 for 5 days

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (intra-osseous UCB with hMSC co-transplant)

total-body irradiation RADIATION

Undergo single fraction of reduced intensity conditioning (RIC) regimen of 200 cGy TBI without shielding on day -1

Also known as: TBI

Treatment (intra-osseous UCB with hMSC co-transplant)

cyclosporine DRUG

Initiated in patients on the day -5. Cyclosporine will be administered orally or intravenously at 2 mg/kg/dose every 12 hours for 2-hour period. Cyclosporine will continue until day +100

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Treatment (intra-osseous UCB with hMSC co-transplant)

mycophenolate mofetil DRUG

Given at 1g intravenously or orally twice daily from day -5 to +100, or as clinically indicated.

Also known as: Cellcept, MMF

Treatment (intra-osseous UCB with hMSC co-transplant)

umbilical cord blood transplantation PROCEDURE

Following RIC, on day T+0, dimethylsulphoxide will be removed from the cord blood cells and given as transplant.

Also known as: cord blood transplantation, transplantation, umbilical cord blood, UCB transplantation

Treatment (intra-osseous UCB with hMSC co-transplant)

mesenchymal stem cell transplantation PROCEDURE

The total dosage of hMSC will be 2x10\^6cells/kg (+/-20%).

Also known as: hMSC transplantation

Treatment (intra-osseous UCB with hMSC co-transplant)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have one of the following malignancies:
• Acute myelogenous leukemia (AML): high-risk AML including:
• Antecedent hematological disease (e.g., myelodysplasia \[MDS\])
• Treatment-related leukemia
• Complete remission (first complete remission \[CR1\]) with poor-risk cytogenetics or molecular markers (e.g. fms-related tyrosine kinase 3 \[Flt 3\] mutation, 11q23, del 5, del 7, complex cytogenetics)
• Second complete remission (CR2) or third complete remission (CR3)
• Induction failure or first relapse with either
• ≤ 10% blasts in the marrow and/or
• ≤ 5% blasts in the peripheral blood
• Acute lymphoblastic leukemia (ALL)
• High-risk CR1 including:
• Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22)or 11q23 rearrangements)
• Presence of minimal disease by flow cytometry after 2 or more cycles of chemotherapy
• No complete remission (CR) within 4 weeks of initial treatment
• Induction failure

You may not qualify if:

• Patients with inadequate Organ Function as defined by:
• Creatinine clearance \< 30 ml/min
• Bilirubin ≥ 2 x institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≥ 2 x institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≥ 2 x institutional upper limit of normal
• Corrected diffusing capacity of the lung for carbon monoxide (DLCOcorr) \< 40% normal
• Left ventricular ejection fraction \< 35%
• Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding women are excluded from this study

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Primary Myelofibrosis; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasms

Interventions

Cyclophosphamide; fludarabine phosphate; Whole-Body Irradiation; Cyclosporine; Mycophenolic Acid; Cord Blood Stem Cell Transplantation; Transplantation; Mesenchymal Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Myeloproliferative Disorders; Lymphoma; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Surgical Procedures, Operative

Study Officials

• Leland Metheny, MD

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 2, 2014
• First Posted: July 4, 2014
• Study Start: July 22, 2015
• Primary Completion: December 19, 2019
• Study Completion: February 7, 2020
• Last Updated: December 4, 2020

Record last verified: 2020-12

Locations

US (1)