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

NCT03096782 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2016-0051NCI-2018-01236
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Biphenotypic Leukemia; Acute Leukemia; Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chemotherapy-Related Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Hodgkin Lymphoma; Langerhans Cell Histiocytosis; Minimal Residual Disease; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Refractory Acute Lymphoblastic Leukemia; Refractory Myelodysplastic Syndrome; Small Lymphocytic Lymphoma; Therapy-Related Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Disease-free Survival

  Up to12 months

• Overall Survival

  Up to 12 months after transplant

Study Arms (1)

Chemotherapy and Cord blood transfusion

EXPERIMENTAL

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.

Biological: Anti-Thymocyte Globulin; Drug: Busulfan; Drug: Clofarabine; Drug: Cyclophosphamide; Biological: Filgrastim-sndz; Drug: Fludarabine; Drug: Melphalan; Drug: Mycophenolate Mofetil; Biological: Rituximab; Drug: Tacrolimus; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation

Interventions

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin

Chemotherapy and Cord blood transfusion

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Chemotherapy and Cord blood transfusion

Clofarabine DRUG

Given IV

Also known as: Clofarex, Clolar

Chemotherapy and Cord blood transfusion

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Chemotherapy and Cord blood transfusion

Filgrastim-sndz BIOLOGICAL

Given SC

Also known as: Filgrastim Biosimilar Filgrastim-sndz, Zarxio

Chemotherapy and Cord blood transfusion

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Chemotherapy and Cord blood transfusion

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine nitrogen mustard, Sarcoclorin, Sarkolysin, WR-19813

Chemotherapy and Cord blood transfusion

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: Cellcept, MMF

Chemotherapy and Cord blood transfusion

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, 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

Chemotherapy and Cord blood transfusion

Tacrolimus DRUG

Given IV

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Chemotherapy and Cord blood transfusion

Total-Body Irradiation RADIATION

Undergo total body irradiation

Also known as: Total Body Irradiation, Whole-Body Irradiation

Chemotherapy and Cord blood transfusion

Umbilical Cord Blood Transplantation PROCEDURE

Undergo cord blood transplant

Also known as: Cord Blood Transplantation, UCB transplantation

Chemotherapy and Cord blood transfusion

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Leukemia, Biphenotypic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Hodgkin Disease; Histiocytosis, Langerhans-Cell; Neoplasm, Residual; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Lymphoma, Non-Hodgkin

Interventions

Antilymphocyte Serum; thymoglobulin; Busulfan; Clofarabine; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine; Melphalan; Mycophenolic Acid; Rituximab; CT-P10; Tacrolimus; Whole-Body Irradiation; Cord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

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; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Myelodysplastic-Myeloproliferative Diseases; Lymphoma; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Histiocytosis; Neoplastic Processes; Anemia, Refractory; Anemia

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Macrolides; Lactones; Radiotherapy; Therapeutics; Investigative Techniques; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Amanda Olson, MD / Stem Cell Transplantation
• Organization: University of Texas MD Anderson Cancer Center

alolson@mdanderson.org

713-745-1505

Study Officials

• Amanda Olson

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: March 30, 2017
• Study Start: October 13, 2017
• Primary Completion: September 20, 2022
• Study Completion: September 20, 2022
• Last Updated: October 11, 2023
• Results First Posted: June 28, 2023

Record last verified: 2023-10

Locations

US (1)