Clinical Trials /

UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep

NCT02722668

Description:

This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen with modifications based on factors including diagnosis, disease status, and prior treatment. Single or double unit selected according to current University of Minnesota umbilical cord blood graft selection algorithm.

Related Conditions:
  • Acute Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Anaplastic Large Cell Lymphoma
  • Burkitt Lymphoma
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Chronic Myeloid Leukemia
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Lymphoblastic Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myeloproliferative Neoplasm
  • Prolymphocytic Leukemia
  • T-Cell and NK-Cell Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep
  • Official Title: Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Hematological Diseases Using a Non-Myeloablative Preparative Regimen

Clinical Trial IDs

  • ORG STUDY ID: 2015LS149
  • SECONDARY ID: MT2015-17
  • NCT ID: NCT02722668

Conditions

  • Acute Leukemia
  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia/Lymphoma
  • Burkitt's Lymphoma
  • Natural Killer Cell Malignancies
  • Chronic Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • Large-cell Lymphoma
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Relapsed Chronic Lymphocytic Leukemia
  • Relapsed Small Lymphocytic Lymphoma
  • Marginal Zone B-cell Lymphoma
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle-cell Lymphoma
  • Prolymphocytic Leukemia
  • Bone Marrow Failure Syndromes
  • Myeloproliferative Neoplasms/Myelofibrosis
  • Biphenotypic/Undifferentiated/Prolymphocytic Leukemias
  • MRD Positive Leukemia
  • Leukemia or MDS in Aplasia
  • Relapsed T-Cell Lymphoma
  • Relapsed Multiple Myeloma
  • Plasma Cell Leukemia

Interventions

DrugSynonymsArms
FludarabineFludaraNo ATG
CyclophosphamideCytoxanNo ATG
MMFMycophenolate MofetilNo ATG
SirolimusRapamycinNo ATG
Umbilical cord blood cell infusionUCBNo ATG
ATGAnti-thymocyte GlobulinATG

Purpose

This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen with modifications based on factors including diagnosis, disease status, and prior treatment. Single or double unit selected according to current University of Minnesota umbilical cord blood graft selection algorithm.

Trial Arms

NameTypeDescriptionInterventions
No ATGExperimentalHematologic malignancy patients who have received a previous autologous transplant or ≥ 2 cycles of multi-agent chemotherapy within the 3 months previous to umbilical cord blood transplantation.
  • Fludarabine
  • Cyclophosphamide
  • MMF
  • Sirolimus
ATGExperimentalHematologic malignancy patients who have not been treated with prior autologous transplant or ≤ 1 cycle of chemotherapy in the 3 months previous to umbilical cord blood transplantation, should receive Anti-thymocyte Globulin (ATG) as part of their conditioning regimen.
  • Fludarabine
  • Cyclophosphamide
  • MMF
  • Sirolimus

Eligibility Criteria

        Inclusion Criteria:

          -  Age, Performance Status, and Graft Criteria

               -  <70 years of age with no matched 5/6 or 6/6 sibling donor - patients ≥ 70 and ≤
                  75 years of age may be eligible if they have a Co-Morbidity score ≤ 2
                  (http://www.qxmd.com/calculate-online/hematology/hct-ci)

               -  Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years)

               -  UCB graft selected according to current University of Minnesota umbilical cord
                  blood graft selection algorithm

          -  Eligible Diseases All diseases listed below are advanced hematologic malignancies not
             curable by conventional chemotherapy. Responses to conventional treatment range from
             zero to 30% but are typically short lived.

               -  Acute Leukemias: Must be in remission by morphology (<5% blasts). Note
                  cytogenetic relapse or persistent disease without morphologic relapse is
                  acceptable. Also a small percentage of blasts that is equivocal between marrow
                  regeneration vs. early relapse are acceptable provided there are no associated
                  cytogenetic markers consistent with relapse.

                    -  Acute Myeloid Leukemia (AML) and related precursor neoplasms: 2nd or greater
                       complete remission (CR); first complete remission (CR1) in patients > 60
                       years old; CR1 in ≤ 60 years old that is NOT considered as favorable-risk.
                       Favorable risk AML is defined as having one of the following:

                         -  t(8,21) without cKIT mutation

                         -  inv(16) or t(16;16) without cKIT mutation

                         -  Normal karyotype with mutated NPM1 and wild type FLT-ITD

                         -  Normal karyotype with double mutated CEBPA

                         -  Acute prolymphocytic leukemia (APL) in first molecular remission at the
                            end of consolidation

                    -  Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1
                       unable to tolerate consolidation chemotherapy due to chemotherapy-related
                       toxicities; CR1 high-risk ALL. High risk ALL is defined as having one of the
                       following:

                         -  Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11),
                            other MLL rearrangements, IKZF1

                         -  30 years of age or older at diagnosis

                         -  White blood cell counts of greater than 30,000/mcL (B-ALL) or greater
                            than 100,000/mcL (T-ALL) at diagnosis

                         -  CNS leukemia involvement during the course of disease

                         -  Slow cytologic response (>10% lymphoblasts in bone marrow on Day 14 of
                            induction therapy)

                         -  Evidence of persistent immonophenotypic or molecular minimal residual
                            disease (MRD) at the end of induction and consolidation therapy

               -  Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR

               -  Chronic myelogenous leukemia in chronic or accelerated phase, or CML blast crisis
                  in morphological remission (<5% blasts): Chronic phase patients must have failed
                  at least two tyrosine kinase inhibitors, been intolerant to all available TKIs,
                  or have T315I mutation.

               -  Myelodysplastic syndrome: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO
                  classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC < 0.8, Anemia or
                  thrombocytopenia requiring transfusion; Poor or very poor risk cytogenetics based
                  on IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be < 5% by bone
                  marrow aspirate morphology. If ≥5% blasts, patient requires chemotherapy for
                  cytoreduction to <5% blasts prior to transplantation.

               -  MRD positive leukemia (AML, ALL or accelerated/blast phase CML). Selected
                  patients in morphologic CR, but with positive immunophenotypic (flow cytometry)
                  or molecular evidence of MRD may be eligible if recent chemotherapy has not
                  resulted in MRD negative status.

               -  Leukemia or MDS in aplasia. These patients may be taken to transplant if after
                  induction therapy they remain with aplastic bone marrow and no morphological or
                  flow-cytometry evidence of disease ≥ 28 days post-therapy. These high risk
                  patients will be analyzed separately.

               -  Burkitt's lymphoma in CR2 or subsequent CR

               -  Relapsed T-Cell Lymphoma that is chemotherapy sensitive in CR/PR that has failed
                  or ineligible for an autologous transplant.

               -  Natural killer cell malignancies

               -  Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy
                  sensitive disease who are ineligible for an autologous transplant.

               -  Relapsed Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),
                  marginal zone B-cell lymphoma, follicular lymphoma which have progressed within
                  12 months 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 should be considered for debulking chemotherapy
                  before transplant. Patients with refractory disease are eligible, unless bulky
                  disease and an estimated tumor doubling time of less than one month.

               -  Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are
                  eligible after initial therapy if chemotherapy sensitive.

               -  Relapsed Multiple Myeloma that is chemotherapy sensitive and has failed or
                  ineligible for an autologous transplant.

               -  Plasma Cell Leukemia after initial therapy if achieved at least in partial
                  remission; or relapsed and achieved subsequent remission (CR/PR)

               -  Acquired Bone marrow failure syndromes, except for Fanconi anemia

               -  Myeloproliferative Neoplasms/Myelofibrosis

               -  Other Leukemia Subtypes: A major effort in the field of hematology is to identify
                  patients who are of high risk for treatment failure so that patients can be
                  appropriately stratified to either more (or less) intensive therapy. This effort
                  is continually ongoing and retrospective studies identify new disease features or
                  characteristics that are associated with treatment outcomes. Therefore, if new
                  features are identified after the writing of this protocol, patients can be
                  enrolled with the approval of two members of the study committee.

          -  Additional Criteria for Bulky Disease (lymphomas)

               -  If stable disease is best response, the largest residual nodal mass must < 5 cm
                  (approximately)

               -  If response to previous therapy, the largest residual mass must represent a 50%
                  reduction and be < 7.5 cm (approximately)

          -  Organ Function Criteria

        Adequate organ function is defined as:

          -  Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia
             and left ventricular ejection fraction > 40%. For children that are not able to
             cooperate with MUGA and echocardiography, such should be clearly stated in the
             physician's note.

          -  Pulmonary: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements. For
             children that are not able to cooperate with PFTs, a pulse oximetry with exercise
             should be attempted. If neither test can be obtained it should be clearly stated in
             the physician's note.

          -  Liver: Transaminases ≤ 5 x upper limit of normal (ULN) and total bilirubin ≤ 2.5 mg/dL
             except for patients with Gilbert's syndrome or hemolysis

          -  Renal: Creatinine ≤ 2.0 mg/dl (adults) and creatinine clearance ≥ 40 mL/min
             (pediatrics). Adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction
             must have estimated creatinine clearance ≥ 40 ml/min/1.73m^2. Adequate performance
             status is defined as Karnofsky score ≥ 70% (≥ 16 years of age) or Lansky score ≥ 50
             (pediatrics)

               -  Sexually active females of childbearing potential and males with partners of
                  child-bearing potential must agree to use adequate birth control during study
                  treatment.

               -  Voluntary written consent (adult or parent/guardian with presentation of the
                  minor information sheet, if appropriate)

        Exclusion Criteria:

          -  Pregnant or breast feeding. The agents used in this study include Pregnancy Category
             D: known to cause harm to a fetus. Females of childbearing potential must have a
             negative pregnancy test prior to starting therapy.

          -  Untreated active infection

          -  Active HIV infection or known HIV positive serology

          -  Less than 3 months since prior myeloablative transplant

          -  Evidence of progressive disease by imaging modalities or biopsy - persistent PET
             activity, though possibly related to lymphoma, is not an exclusion criterion in the
             absence of CT changes indicating progression.

          -  CML in blast crisis

          -  Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on
             salvage therapy.

          -  Active central nervous system malignancy
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Probability of Acute Graft Versus Host Disease (GVHD)
Time Frame:Day 100
Safety Issue:
Description:Simple proportions will be used to estimate the probability of grade II-IV actue GVHD.

Secondary Outcome Measures

Measure:Incidence of Acute GVHD
Time Frame:Day 100
Safety Issue:
Description:Percentage of patients with grade III-IV acute GVHD.
Measure:Transplant related mortality
Time Frame:6 months post transplant
Safety Issue:
Description:
Measure:Chimerism
Time Frame:Day 21
Safety Issue:
Description:Percentage of subjects with donor chimerism.
Measure:Chimerism
Time Frame:Day 100
Safety Issue:
Description:Percentage of subjects with donor chimerism.
Measure:Chimerism
Time Frame:Day 180
Safety Issue:
Description:Percentage of subjects with donor chimerism.
Measure:Chimerism
Time Frame:1 year post transplant
Safety Issue:
Description:Percentage of subjects with donor chimerism.
Measure:Neutrophil Engraftment
Time Frame:Day 42
Safety Issue:
Description:Percentage of subjects with neutrophil engraftment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Masonic Cancer Center, University of Minnesota

Trial Keywords

  • AML
  • ALL
  • CML
  • CLL
  • SLL

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