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Myeloablative Allo HSCT With Related or Unrelated Donor for Heme Disorders

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ClinicalTrials.gov Identifier: NCT03314974
Recruitment Status : Recruiting
First Posted : October 19, 2017
Last Update Posted : March 22, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
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 Biological: HSCT with TBI Regimen Biological: HSCT with Non-TBI Regimen Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Myeloablative Allogeneic Hematopoietic Cell Transplantation Using a Related or Unrelated Donor for the Treatment of Hematological Diseases
Estimated Study Start Date : December 10, 2019
Estimated Primary Completion Date : November 10, 2023
Estimated Study Completion Date : November 10, 2024


Arm Intervention/treatment
Experimental: TBI Regimen Biological: HSCT with TBI Regimen
Day -5 to -2: Total Body Irradiation Day 0: Hematopoietic Stem Cell Transplantation Day +3 to +4: Cyclophosphamide Day +5: Tacrolimus from day +5 until taper day +100 (day +60 for peds if no acute or chronic GVHD present) Day +5: Mycophenolate mofetil through day +35 or 7 days after engraftment, whichever day is later, if no acute GVHD
Other Name: Hematopoietic Stem Cell Transplantation

Experimental: Non-TBI Regimen Biological: HSCT with Non-TBI Regimen
Day -5 to Day -2: Busulfan and Fludaribine Day 0: Hematopoietic Stem Cell Transplantation Day +3 to +4: Cyclophosphamide Day +5: Tacrolimus from day +5 until taper day +100 (day +60 for peds if no acute or chronic GVHD present) Day +5: Mycophenolate mofetil through day +35 or 7 days after engraftment, whichever day is later, if no acute GVHD
Other Name: Hematopoietic Stem Cell Transplantation




Primary Outcome Measures :
  1. Chronic GVHD - 1 year [ Time Frame: 1 year ]
    Incidence of chronic GVHD


Secondary Outcome Measures :
  1. Grade II-IV acute GVHD [ Time Frame: Day +100 ]
    Cumulative incidence grade II-IV acute GVHD

  2. Chronic GVHD - 2 years [ Time Frame: 2 years ]
    Incidence of chronic GVHD

  3. Relapse [ Time Frame: 2 years ]
    Cumulative incidence of relapse

  4. Overall survival [ Time Frame: 2 years ]
    Cumulative incidence of overall survival

  5. Treatment-related mortality [ Time Frame: 2 years ]
    Cumulative incidence of treatment-related mortality

  6. Graft-versus-host disease-free, relapse free survival (GRFS) [ Time Frame: 1 year ]
    Cumulative incidence of GRFS

  7. Graft-versus-host disease-free, relapse free survival (GRFS) [ Time Frame: 2 years ]
    Cumulative incidence of GRFS

  8. Neutrophil Engraftment [ Time Frame: Day 42 ]
    Cumulative incidence of Neutrophil Engraftment

  9. Neutrophil Engraftment [ Time Frame: 6 months ]
    Cumulative incidence of Neutrophil Engraftment

  10. Platelet Engraftment [ Time Frame: Day 42 ]
    Cumulative incidence of Platelet Engraftment

  11. Platelet Engraftment [ Time Frame: 6 months ]
    Cumulative incidence of Platelet Engraftment



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03314974


Contacts
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Contact: Tim Krepski (612)-273-2800 tkrespk1@fairview.org

Locations
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United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55337
Contact: Timothy Krepski, RN    612-273-2800    tkrepsk1@Fairview.org   
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Shernan Holtan Masonic Cancer Center, University of Minnesota

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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT03314974     History of Changes
Other Study ID Numbers: 2015LS034
MT2015-29 ( Other Identifier: University of Minnesota )
First Posted: October 19, 2017    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Masonic Cancer Center, University of Minnesota:
AML
ALL
MDS
NHL
CLL
CML
SLL
Additional relevant MeSH terms:
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Leukemia, Plasma Cell
Burkitt Lymphoma
Lymphoma
Leukemia
Multiple Myeloma
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma, B-Cell, Marginal Zone
Leukemia, Prolymphocytic
Leukemia, Myelomonocytic, Juvenile
Waldenstrom Macroglobulinemia
Anemia
Myeloproliferative Disorders
Anemia, Refractory
Pancytopenia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Myeloid
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias