Clinical Trials /

Myeloablative Allo HSCT With Related or Unrelated Donor for Heme Disorders

NCT03314974

Description:

This is a Phase II study of allogeneic hematopoietic stem cell transplant (HCT) using a myeloablative preparative regimen (of either total body irradiation (TBI); or, fludarabine/busulfan for patients unable to receive further radiation). followed by a post-transplant graft-versus-host disease (GVHD) prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF).

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Acute Undifferentiated Leukemia
  • Burkitt Lymphoma
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Chronic Myeloid Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Juvenile Myelomonocytic Leukemia
  • Leukemia
  • Lymphoblastic Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myelofibrosis
  • Myeloproliferative Neoplasm
  • Natural Killer Cell Lymphoblastic Leukemia/Lymphoma
  • Non-Hodgkin Lymphoma
  • Plasma Cell Leukemia
  • Prolymphocytic Leukemia
  • Refractory Anemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Myeloablative Allo HSCT With Related or Unrelated Donor for Heme Disorders
  • Official Title: Myeloablative Allogeneic Hematopoietic Cell Transplantation Using a Related or Unrelated Donor for the Treatment of Hematological Diseases

Clinical Trial IDs

  • ORG STUDY ID: 2015LS034
  • SECONDARY ID: MT2015-29
  • NCT ID: NCT03314974

Conditions

  • Acute Leukemia
  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia
  • Lymphoma
  • Chronic Myelogenous Leukemia
  • Plasma Cell Leukemia
  • Myeloproliferative Neoplasms
  • Myelofibrosis
  • Myelodysplasia
  • Refractory Anemia
  • High Risk Anemia
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Marginal Zone B-Cell Lymphoma
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle-Cell Lymphoma
  • Prolymphocytic Leukemia
  • Diffuse Large Cell Non Hodgkins Lymphoma
  • Lymphoblastic Lymphoma
  • Burkitt Lymphoma
  • High Grade Non-Hodgkin's Lymphoma, Adult
  • Multiple Myeloma
  • Juvenile Myelomonocytic Leukemia
  • Biphenotypic/Undifferentiated/Prolymphocytic Leukemias
  • MRD Positive Leukemia
  • Natural Killer Cell Malignancies
  • Acquired Bone Marrow Failure Syndromes

Interventions

DrugSynonymsArms
HSCT with TBI RegimenHematopoietic Stem Cell TransplantationTBI Regimen
HSCT with Non-TBI RegimenHematopoietic Stem Cell TransplantationNon-TBI Regimen

Purpose

This is a Phase II study of allogeneic hematopoietic stem cell transplant (HCT) using a myeloablative preparative regimen (of either total body irradiation (TBI); or, fludarabine/busulfan for patients unable to receive further radiation). followed by a post-transplant graft-versus-host disease (GVHD) prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF).

Trial Arms

NameTypeDescriptionInterventions
TBI RegimenExperimental
  • HSCT with TBI Regimen
Non-TBI RegimenExperimental
  • HSCT with Non-TBI Regimen

Eligibility Criteria

        Inclusion Criteria:

          -  Age, Performance Status, Consent:

               -  Age: ≤ 55 years of age

               -  Performance Status: Karnofsky ≥ 80%, Lansky play score ≥ 70

               -  Consent: Voluntary written consent (adult or legally authorized representative;
                  or parental/guardian)

          -  Adequate Organ Function:

               -  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/1.73m2

               -  Hepatic: Bilirubin, AST, alkaline phosphatase <4 times the upper limit of
                  institutional normal

               -  Pulmonary: Diffusion capacity of oxygen, corrected for hemoglobin, > 50% of
                  predicted

               -  Cardiac: Absence of decompensated congestive heart failure, or uncontrolled
                  arrhythmia and left ventricular ejection fraction > 45%. For children not able to
                  cooperate with MUGA or echocardiography, such should be clearly stated in the
                  physician's documentation

          -  Donor Availability: Patients considered for transplantation must have a sufficient
             graft as based on current criteria of the University of Minnesota Blood and Marrow
             Transplantation Program

          -  Eligible Diseases and Status: Patients are eligible unless their treatment is to be
             guided by a higher priority protocol.

          -  Acute Leukemias: Must be in remission by morphology (≤5% blasts). 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

          -  Very high risk pediatric patients with AML: Patients <21 years, however, are eligible
             with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of
             chemotherapy.

          -  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

          -  Very high risk pediatric patients with ALL: patients <21 years are also considered
             high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction
             or M3 marrow at the end of induction. They are eligible once they achieve a complete
             remission.

          -  Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in
             first chronic phase (CP1) patient must have failed or be intolerant to one or more
             tyrosine kinase inhibitors.

          -  Plasma Cell Leukemia after initial therapy, in patients who have achieved at least a
             partial remission

          -  Myeloproliferative Neoplasms/Myelofibrosis, either primary as a result of polycythemia
             vera or essential thrombocythemia, with disease risk of intermediate or high-risk
             according to DIPSS criteria. Blasts must be <10% by bone marrow aspirate morphology.

          -  Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia
             with severe pancytopenia, transfusion dependence, or high risk cytogenetics or
             molecular features. Blasts must be < 10% by a representative bone marrow aspirate
             morphology.

          -  Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone
             B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease
             progression/relapse within 12 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 (nodal mass greater than 5 cm) should be
             considered for debulking chemotherapy before transplant.

          -  Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible
             after initial therapy in CR1+ or PR1+.

          -  Diffuse large Cell NHL > CR/> PR: Patients in CR/PR with initial short remission (<6
             months) are eligible, or those who have failed/or are not eligible for autologous
             transplant.

          -  Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial
             therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.

          -  Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response
             lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this
             protocol after initial therapy.

          -  Juvenile myelomonocytic leukemia

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

          -  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.

          -  Natural Killer Cell Malignancies

          -  Acquired Bone Marrow Failure Syndromes except for Fanconi Anemia or Dyskeratosis
             Congenita

          -  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.

        Exclusion Criteria:

          -  Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after
             > 2 salvage regimens)

          -  CML in blast crisis

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

          -  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.

          -  Active central nervous system malignancy

          -  if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18
             years old prior myeloablative allotransplant or autologous transplant

          -  Active HIV infection or known HIV positive serology

          -  active uncontrolled infection

          -  Pregnant or breastfeeding. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Chronic GVHD - 1 year
Time Frame:1 year
Safety Issue:
Description:Incidence of chronic GVHD

Secondary Outcome Measures

Measure:Grade II-IV acute GVHD
Time Frame:Day +100
Safety Issue:
Description:Cumulative incidence grade II-IV acute GVHD
Measure:Chronic GVHD - 2 years
Time Frame:2 years
Safety Issue:
Description:Incidence of chronic GVHD
Measure:Relapse
Time Frame:2 years
Safety Issue:
Description:Cumulative incidence of relapse
Measure:Overall survival
Time Frame:2 years
Safety Issue:
Description:Cumulative incidence of overall survival
Measure:Treatment-related mortality
Time Frame:2 years
Safety Issue:
Description:Cumulative incidence of treatment-related mortality
Measure:Graft-versus-host disease-free, relapse free survival (GRFS)
Time Frame:1 year
Safety Issue:
Description:Cumulative incidence of GRFS
Measure:Graft-versus-host disease-free, relapse free survival (GRFS)
Time Frame:2 years
Safety Issue:
Description:Cumulative incidence of GRFS
Measure:Neutrophil Engraftment
Time Frame:Day 42
Safety Issue:
Description:Cumulative incidence of Neutrophil Engraftment
Measure:Neutrophil Engraftment
Time Frame:6 months
Safety Issue:
Description:Cumulative incidence of Neutrophil Engraftment
Measure:Platelet Engraftment
Time Frame:Day 42
Safety Issue:
Description:Cumulative incidence of Platelet Engraftment
Measure:Platelet Engraftment
Time Frame:6 months
Safety Issue:
Description:Cumulative incidence of Platelet Engraftment

Details

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

Trial Keywords

  • AML
  • ALL
  • MDS
  • NHL
  • CLL
  • CML
  • SLL

Last Updated