Infusion of Off-the-Shelf Expanded Cord Blood Cells to Augment Cord Blood Transplant in Patients With Hematologic Malignancies

NCT01175785 | Completed Phase 2 FDA Drug

• 5 other identifiers: 2378.00NCI-2010-014262378P30CA015704RC2HL101844
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying the safety and potential efficacy of infusing non-human leukocyte antigen matched ex vivo expanded cord blood progenitors with one or two unmanipulated umbilical cord blood units for transplantation following conditioning with fludarabine phosphate, cyclophosphamide and total body irradiation, and immunosuppression with cyclosporine and mycophenolate mofetil for patients with hematologic malignancies. Chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation given before an umbilical cord blood transplant stops the growth of leukemia cells and works to prevent the patient's immune system from rejecting the donor's stem cells. The healthy stem cells from the donor's umbilical cord blood help the patient's bone marrow make new red blood cells, white blood cells, and platelets. It may take several weeks for these new blood cells to grow. During that period of time, patients are at increased risk for bleeding and infection. Faster recovery of white blood cells may decrease the number and severity of infections. Studies have shown that counts recover more quickly when more cord blood cells are given with the transplant. We have developed a way of growing or "expanding" the number of cord blood cells in the lab so that there are more cells available for transplant. We are doing this study to find out whether or not giving these expanded cells along with one or two unexpanded cord blood units is safe and if use of expanded cells can decrease the time it takes for white blood cells to recover after transplant. We will study the time it takes for blood counts to recover, which of the two or three cord blood units makes up the patient's new blood system, and how quickly immune system cells return.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (14)

• Time to neutrophil engraftment

  Defined as the first of 2 consecutive days in which the absolute neutrophil count (ANC) \>= 500.

  By day 42

• Time to platelet engraftment

  By day 100

• Overall survival

  Day 100

• Overall survival

  Day 180

• Overall survival

  1 year

• Overall survival

  2 years

• Event-free survival

  Day 100

• Event-free survival

  Day 180

• Event-free survival

  1 year

• Event-free survival

  2 years

• Incidence of severe (grades 3-4) acute GVHD

  Up to day 100

• Incidence of grade greater than or equal to 3 infusional toxicity

  Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.

  By day 100

• Primary graft failure

  Defined as failure to achieve ANC \>= 500/mm\^3 of donor origin.

  By day 42

• Secondary graft failure

  Up to 2 years

Study Arms (1)

Treatment (chemo, radiation, transplant, GVHD prophylaxis)

EXPERIMENTAL

Patients receive fludarabine phosphate IV over 1 hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI twice daily on days -4 to -1. Patients undergo unmanipulated single- or double-unit umbilical cord blood transplantation on day 0 and receive ex vivo-expanded cord blood progenitor cells IV over 4 hours following the last unmanipulated cord blood infusion. Patients initially receive CSP IV over 1 hour beginning on day -3. CSP may be given PO when the patient can tolerate oral medications and has a normal gastrointestinal transit time. CSP is given until day 100, and may taper on day 101 if there is no graft versus host disease. Patients also receive MMF IV every 8 hours on days 0 to 7 and then may receive MMF PO beginning day 8 to 30. MMF is continued for a minimum of 30 days or until 7 days after blood counts recover whichever is later. If there is no evidence of acute GVHD and donor CD3 engraftment is at least 50% from one donor MMF may be tapered.

Procedure: umbilical cord blood transplantation; Drug: fludarabine phosphate; Drug: cyclophosphamide; Biological: ex vivo-expanded cord blood progenitor cell infusion; Radiation: total-body irradiation; Drug: cyclosporine; Drug: mycophenolate mofetil; Other: laboratory biomarker analysis

Interventions

umbilical cord blood transplantation PROCEDURE

Undergo unmanipulated umbilical cord blood transplant

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

Treatment (chemo, radiation, transplant, GVHD prophylaxis)

fludarabine phosphate DRUG

Given IV

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

Treatment (chemo, radiation, transplant, GVHD prophylaxis)

cyclophosphamide DRUG

Given IV

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

Treatment (chemo, radiation, transplant, GVHD prophylaxis)

ex vivo-expanded cord blood progenitor cell infusion BIOLOGICAL

Undergo ex-vivo expanded cryopreserved cord blood progenitor cells

Also known as: Dilanubicel, NLA101

Treatment (chemo, radiation, transplant, GVHD prophylaxis)

total-body irradiation RADIATION

Undergo TBI

Also known as: TBI

Treatment (chemo, radiation, transplant, GVHD prophylaxis)

cyclosporine DRUG

Given IV

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

Treatment (chemo, radiation, transplant, GVHD prophylaxis)

mycophenolate mofetil DRUG

Given IV and PO

Also known as: Cellcept, MMF

Treatment (chemo, radiation, transplant, GVHD prophylaxis)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (chemo, radiation, transplant, GVHD prophylaxis)

Eligibility Criteria

• Age: 6 Months - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Acute myeloid leukemia:
• High risk complete response (CR)1 as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7, or as defined by referring institution treatment protocol), \>= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; \>= CR2
• All patients must be in CR as defined by hematologic recovery and \< 5% blasts by morphology within the bone marrow and a cellularity of \>= 15%
• Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the Principal Investigator, Colleen Delaney prior to enrollment
• Acute lymphoblastic leukemia:
• High risk CR1 \[for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed lineage leukemia (MLL) rearrangements, hypodiploid\]
• Greater than 1 cycle to obtain CR
• \>= CR2
• All patients must be in CR as defined by hematologic recovery and \< 5% blasts by morphology within the bone marrow and a cellularity of \>= 15%
• Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the Principal Investigator, Colleen Delaney prior to enrollment
• 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
• Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate 2 (Int-2) or high risk (i.e., refractory anemia with excess myeloblasts \[RAEB\], refractory anemia with excess blasts in transformation \[RAEB-T\]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be \< 10% by a representative bone marrow aspirate morphology
• Karnofsky (\>= 16 years old) \>= 70%
• Lansky (\< 16 years old) \>= 50%
• Calculated creatinine clearance must be \> 60 mL and serum creatinine =\< 2 mg/dL (adults)

You may not qualify if:

• Uncontrolled viral or bacterial infection at the time of study enrollment
• Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
• History of human immunodeficiency virus (HIV) infection
• Pregnant or breastfeeding
• 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

Sponsors & Collaborators

• Nohla Therapeutics, Inc.: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator
• Fred Hutchinson Cancer Center: collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Milano F, Thur LA, Blake J, Delaney C. Infusion of Non-HLA-Matched Off-the-Shelf Ex Vivo Expanded Cord Blood Progenitors in Patients Undergoing Cord Blood Transplantation: Result of a Phase II Clinical Trial. Front Cell Dev Biol. 2022 Apr 4;10:835793. doi: 10.3389/fcell.2022.835793. eCollection 2022.

  PMID: 35445027 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Congenital Abnormalities; Leukemia, Myeloid, Chronic-Phase; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts

Interventions

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

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

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

Study Officials

• Colleen Delaney

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2010
• First Posted: August 5, 2010
• Study Start: August 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: March 5, 2019

Record last verified: 2019-02

Locations

US (1)