Umbilical Cord Blood Transplant With Added Sugar and Chemotherapy and Radiation Therapy in Treating Patients With Leukemia or Lymphoma

Cord Blood Ex-Vivo MSC Expansion Plus Fucosylation to Enhance Homing and Engraftment

This phase II trial studies how well an umbilical cord blood transplant with added sugar works with chemotherapy and radiation therapy in treating patients with leukemia or lymphoma. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The umbilical cord blood cells will be grown ("expanded") on a special layer of cells collected from the bone marrow of healthy volunteers in a laboratory. A type of sugar will also be added to the cells in the laboratory that may help the transplant to "take" faster.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Non-Hodgkin Lymphoma; Acute Leukemia; Myelodysplastic Syndrome; Refractory Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Langerhans Cell Histiocytosis; Refractory Acute Lymphoblastic Leukemia; Minimal Residual Disease; Small Lymphocytic Lymphoma; Therapy-Related Myelodysplastic Syndrome; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Biphenotypic Leukemia; Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Lymphoblastic Leukemia in Remission; Chemotherapy-Related Leukemia
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Rituximab; Biological: Filgrastim-sndz; Drug: Melphalan; Drug: Clofarabine; Biological: Anti-Thymocyte Globulin; Drug: Busulfan; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and feasibility of transplantation of cord blood which is expanded in mesenchymal precursor cell (MPC) co-cultures then fucosylated with fucosyltransferase (FT)-VI and guanosine diphosphate (GDP) fucose prior to infusion in patients with hematologic malignancies following high-dose therapy.

II. To evaluate the time to engraftment using expanded fucosylated cord blood.

SECONDARY OBJECTIVES:

I. To evaluate the rate and severity of graft versus host disease. II. To evaluate the rates of infectious complications. III. To evaluate the rates of disease-free and overall survival.

Summary: All patients receive Busulfan as per standard of care. Busulfan test dose can be administered either as an outpatient prior to admission or as an inpatient on Day -10.

Busulfan pharmacokinetics will be performed with the test dose and the first dose on Day -7 per standard of care. The doses of Days -6, -5, and -4 will be subsequently adjusted to target an AUC of 4,000 microMol.min-1. In the event that PK adjusting were not possible a dose of busulfan of 130 mg/m2 will be administered.

GVHD PROPHYLAXIS: All patients receive mycofenolate mofetil IV over 2 hours or orally (PO) twice daily (BID) on days -3 with a taper beginning on day 100 in the absence of GVHD, tacrolimus IV or PO starting on day -2 for 6 months in the absence of GVHD, and filgrastim-sndz subcutaneously (SC) once daily (QD) starting on day 0 until white blood count begins to recover.

After completion of study treatment, patients are followed up at months 1, 3, 6, and 12.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have one of the following hematologic malignancies: a. Acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, flt3 mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome (MDS), Langerhan's cell histiocytosis, any disease beyond first remission. b. Myelodysplastic syndrome (MDS): MDS International Prognostic Scoring System (IPSS) INT-1 will be enrolled only if the subjects have failed previous leukemia treatments and are transfusion-dependent. MDS may be primary or therapy related, including patients that will be considered for transplant. Including the following categories: 1) Revised IPSS intermediate and high risk groups, 2) MDS with transfusion dependency, 3) Failure to respond or progression of disease on hypomethylating agents, 4) Refractory anemia with excess of blasts, 5) Transformation to acute leukemia, 6) Chronic myelomonocytic leukemia, 7) Atypical MDS/myeloproliferative syndromes, 8) Complex karyotype, abn(3g), -5/5g-, -7/7g-, abn(12p), abn(17p). c. Acute lymphoblastic leukemia (ALL) patients with the following will be considered: induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease. Patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia which excludes > 7 chromosomal abnormalities, or double hit non-Hodgkin's lymphoma. Non-Hodgkin's lymphoma (NHL) in second or third complete remission or relapse (including relapse post autologous hematopoietic stem cell transplant), or relapsed double hit lymphoma. Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease with progression after standard of care therapy or have failed/been intolerant to ibrutinib. Chronic myelogenous leukemia (CML) second chronic phase or accelerated phase. Hodgkin's disease (HD): Induction failure after the first complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant), or those with active disease.
• The first 6 patients must be >= 18 and =< 65 years old. The subsequent patients may include pediatric patients >= 12 and =< 65 years old. Eligibility for pediatric patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician.
• Performance score of at least 80% by Karnofsky or performance score (PS) < 3 (Eastern Cooperative Oncology Group [ECOG]) (age >= 12 years)
• Left ventricular ejection fraction of > 40%.
• Pulmonary function test (PFT) demonstrating a diffusion capacity of least 50% predicted.
• Creatinine =< 1.5 mg/dL for patients 12 years old and older and =< 1 for patients younger than 12 years old.
• Serum glutamate pyruvate transaminase (SGPT) =< to 2.0 x normal.
• Bilirubin =< to 2.0 x normal.
• Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization and willing to use an effective contraceptive measure while on study.
• Patients must have two cord blood (CB) units available which are matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. Each cord must contain at least 1.5 x 10^7 total nucleated cells/Kg recipient body weight (pre-thaw).
• Have identified a backup cells source in case of engraftment failure. The source can be autologous, related or unrelated.
• Patient must not have a 10/10 HLA matched family member or unrelated donor.
• Patients will have a back-up graft from any of the following: an available fraction of autologous marrow; or peripheral blood progenitor cells (PBPCs) harvested and cryopreserved; or family member donor; or a third cord blood unit.
• Prior to initiating chemotherapy in this study, twenty-one or more days must have elapsed since the patient's last radiation or chemotherapy administration (Hydrea, Gleevec and other tyrosine kinase inhibitors [TKI] as well as intrathecal therapy are accepted exceptions).

Exclusion Criteria:

• Patients with known history of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).
• Patients with positive hepatitis serology that is definitive of active disease.
• Active central nervous system (CNS) disease in patient with history of CNS malignancy.
• Patients with chronic active hepatitis or cirrhosis. If positive hepatitis serology, the study chair may deem the patient eligible based on the results of liver biopsy.
• Patients with uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which CB transplantation is proposed), or psychiatric condition that would limit informed consent.
• Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or breast-feeding.
• Pediatric patients with acute lymphoblastic leukemia (ALL) that is t (9,22) positive in first remission are not eligible unless there is evidence of minimal residual disease after initial induction and/or consolidation treatment or the pediatric Philadelphia chromosome positive (Ph+) ALL is clinically refractory to available therapies with evidence of persistence in the bone marrow or peripheral blood.
• Patients with options for treatment that are known to be curative are not eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Chemotherapy and Cord blood transfusion; All patients received Busulfan as per standard of care. Busulfan test dose can be administered either as an outpatient prior to admission or as an inpatient on Day -10. Busulfan pharmacokinetics will be performed with the test dose and the first dose on Day -7 per standard of care. The doses of Days -6, -5, and -4 will be subsequently adjusted to target an AUC of 4,000 microMol.min-1. In the event that PK adjusting were not possible a dose of busulfan of 130 mg/m2 will be administered. GVHD PROPHYLAXIS: All patients also receive mycofenolate mofetil IV over 2 hours or PO BID on days -3 with a taper beginning on day 100 in the absence of GVHD, tacrolimus IV or PO starting on day -2 for 6 months in the absence of GVHD, and filgrastim-sndz SC QD starting on day 0 until white blood count begins to recover.

Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Drug: Fludarabine; Given IV; Other Names: Fluradosa; Biological: Rituximab; Given IV; Other Names: Rituxan; MabThera; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; Monoclonal Antibody IDEC-C2B8; PF-05280586; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; Rituximab Biosimilar IBI301; Rituximab Biosimilar PF-05280586; Rituximab Biosimilar RTXM83; Rituximab Biosimilar SAIT101; RTXM83; Biological: Filgrastim-sndz; Given SC; Other Names: Filgrastim Biosimilar Filgrastim-sndz; Zarxio; Drug: Melphalan; Given IV; Other Names: CB-3025; L-PAM; Alanine Nitrogen Mustard; L-Phenylalanine Mustard; L-Sarcolysin Phenylalanine mustard; L-Sarcolysine; Melphalanum; Phenylalanine Mustard; Sarcoclorin; Sarkolysin; WR-19813; L-sarcolysin; Phenylalanine nitrogen mustard; Drug: Clofarabine; Given IV; Other Names: Clofarex; Clolar; Biological: Anti-Thymocyte Globulin; Given IV; Other Names: ATGAM; ATG; Antithymocyte Globulin; Antithymocyte Serum; ATS; Thymoglobulin; Drug: Busulfan; Given IV; Other Names: Busulfex; Misulfan; Mitosan; Myeloleukon; Myelosan; 1, 4-Bis[methanesulfonoxy]butane; BUS; Bussulfam; Busulfanum; Busulphan; CB 2041; CB-2041; Glyzophrol; GT 41; GT-41; Joacamine; Methanesulfonic Acid Tetramethylene Ester; Methanesulfonic acid, tetramethylene ester; Mielucin; Misulban; Myeleukon; Mylecytan; Myleran; Sulfabutin; Tetramethylene Bis(methanesulfonate); Tetramethylene bis[methanesulfonate]; WR-19508; Drug: Tacrolimus; Given IV; Other Names: Prograf; Hecoria; FK 506; Fujimycin; Protopic; Drug: Mycophenolate Mofetil; Given IV or PO; Other Names: Cellcept; MMF; Radiation: Total-Body Irradiation; Undergo total body irradiation; Other Names: Total Body Irradiation; Whole-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation; Undergo cord blood transplant; Other Names: Cord Blood Transplantation; UCB transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Engraftment	Number of days from transplant when participants achieved engraftment measure by ANC of 0.5 for three consecutive days.	Up to 12 months after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival	Number of participants that were in remission post transplant.	Up to12 months
Overall Survival	Number of participants alive 1 year post transplant.	Up to 12 months after transplant

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Amanda Olson, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2017
• Primary Completion (Actual): September 20, 2022
• Study Completion (Actual): September 20, 2022

Study Registration Dates

• First Submitted: March 21, 2017
• First Submitted That Met QC Criteria: March 24, 2017
• First Posted (Actual): March 30, 2017

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lung Diseases; Disease Attributes; Disease; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Anemia; Neoplastic Processes; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Leukemia, B-Cell; Lung Diseases, Interstitial; Anemia, Refractory; Chronic Disease; Lymphoma; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Hodgkin Disease; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase; Histiocytosis, Langerhans-Cell; Histiocytosis; Neoplasm, Residual; Anemia, Refractory, with Excess of Blasts; Leukemia, Biphenotypic, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Anti-Bacterial Agents; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Cyclophosphamide; Antibodies; Clofarabine; Immunoglobulins; Rituximab; Lenograstim; Melphalan; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Fludarabine; Tacrolimus; Mycophenolic Acid; Busulfan; Thymoglobulin; Antilymphocyte Serum; Mechlorethamine; Nitrogen Mustard Compounds
• Other Study ID Numbers: 2016-0051 (Other Identifier: M D Anderson Cancer Center); NCI-2018-01236 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No