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Trial record 64 of 65 for:    "Viral Infectious Disease" | "Mycophenolic acid"

Allo HSCT Using RIC for Hematological Diseases

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ClinicalTrials.gov Identifier: NCT02661035
Recruitment Status : Recruiting
First Posted : January 21, 2016
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion. The primary objective is to evaluate rates of acute graft-versus-host disease (GVHD) grades II-IV and chronic GVHD with an updated GVHD prophylaxis of tacrolimus and mycophenolate mofetil (MMF) with a non-myeloablative preparative regimen in persons with hematologic malignancies.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Acute Lymphocytic Leukemia Chronic Myelogenous Leukemia Plasma Cell Leukemia Myelodysplastic Syndromes Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma B-Cell Lymphoma Follicular Lymphoma Lymphoplasmacytic Lymphoma Mantle-Cell Lymphoma Prolymphocytic Leukemia Lymphoblastic Lymphoma Burkitt's Lymphoma Non-Hodgkin's Lymphoma Multiple Myeloma Myeloproliferative Syndromes Hematological Diseases Drug: Allopurinol Drug: Fludarabine Drug: Cyclophosphamide Drug: ATG Radiation: TBI Drug: Tacrolimus Drug: MMF Biological: Peripheral Blood Stem Cells Biological: Related or Unrelated Bone Marrow Cells Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning (RIC) for the Treatment of Hematological Diseases [MT2015-32]
Actual Study Start Date : March 9, 2017
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023


Arm Intervention/treatment
Experimental: Reduced Intensity Conditioning
Non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion
Drug: Allopurinol
300 mg/day (for peds -150 mg/m^2/day), day -6 and continue through day 0 or longer if clinically indicated
Other Name: Zyloprim

Drug: Fludarabine
30 mg/m^2 IV over 1 hour, day -6, -5, -4, -3 and -2
Other Name: Fludara

Drug: Cyclophosphamide
50 mg/kg IV over 2 hours, day -6
Other Name: Cytoxan

Drug: ATG
Only for patients with an unrelated donor (URD) and NO multi-agent chemotherapy 3 months prior to transplant. ATG will be administered IV every 12 hours for 6 doses on days -6, -5, and -4 according to institutional guidelines. Methylprednisolone 1 mg/kg IV administered immediately prior to each dose of ATG (6 doses).
Other Name: Anti-thymocyte globulin

Radiation: TBI
All patients who have had previous radiation therapy or TBI will be seen by Radiation Oncology prior to entrance on the protocol for approval for additional 200 cGy of TBI. TBI may be delivered by local guidelines provided the effective dose is equivalent to what is recommended in the TBI Guidelines. The dose of TBI will be 200 cGy given in a single fraction on day -1.
Other Name: Total body irradiation

Drug: Tacrolimus

All patients will receive tacrolimus therapy beginning on day -3. Initial dosing of tacrolimus will be 0.03 - 0.05 mg/kg/day IV; if the recipient body weight is <40 kg, dosing will be 3 times daily, and if ≥ 40 kg, twice daily or per current institutional guidelines.

An attempt will be made to maintain a trough level of 5-10 ng/mL and subsequent dose modifications will be provided by the pharmacist.

Once the patient can tolerate oral medications and has a reasonable oral intake, tacrolimus will be converted to an oral form based on the current IV dose providing normal renal and hepatic function and no major drug interactions.

The timing of the tacrolimus taper will be at the discretion of the treating physician, but in general:

  • Taper begins at day +100 +/- 10 days, if the patient is stably engrafted and has no active GVHD.
  • Taper to zero by reducing dose by approximately 10% a week (rounded to nearest pill size), with a goal to discontinue by month 6 post-HCT.
Other Name: Prograf

Drug: MMF

3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. In obese patients (>125% IBW) 15 mg/kg every 12 hours may be considered. Pediatric patient (<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning day -3. MMF dosing will be monitored and altered as clinically appropriate based on institutional guidelines. Patients will be eligible for MMF dosing and pharmacokinetics studies.

MMF will stop at day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD. (Definition of engraftment is 1st day of 3 consecutive days of absolute neutrophil count [ANC) ≥ 0.5 x 109 /L]). If no donor engraftment, MMF will continue as long as clinically indicated.

Other Name: Mycophenolate Mofetil

Biological: Peripheral Blood Stem Cells
On day 0, patients will receive an allogeneic transplant using PBSC which are CD34+ selected as the donor graft. The graft will be infused over 15-60 minutes after premedication with acetaminophen 650 mg PO and diphenhydramine 25 mg PO/IV with doses adjusted for pediatric patients.

Biological: Related or Unrelated Bone Marrow Cells
On day 0, a target dose of 3 x 10^8 nucleated cells/kg recipient weight will be collected. The graft will be infused over 15-60 minutes after premedication with acetaminophen 650 mg PO and diphenhydramine 25 mg PO/IV with doses adjusted for pediatric patients.




Primary Outcome Measures :
  1. Evaluate rates of acute graft-versus-host disease (GVHD) II-IV [ Time Frame: Day 100 post transplant ]
    Percent of subjects with grade II-IV acute GVHD


Secondary Outcome Measures :
  1. Evaluate rates of chronic GVHD [ Time Frame: 1 year post transplant ]
    Percent of subjects with chronic GVHD

  2. Evaluate neutrophil engraftment without ATG (in siblings) [ Time Frame: Day 42 post transplant ]
    Percent of subjects with neutrophil engraftment without ATG (in siblings)

  3. Evaluate neutrophil engraftment with ATG (in unrelated donors) [ Time Frame: Day 42 post transplant ]
    Percent of subjects with neutrophil engraftment with ATG (in unrelated donors)

  4. Evaluate neutrophil engraftment without ATG (in unrelated donors) [ Time Frame: Day 42 post transplant ]
    Percent of subjects with neutrophil engraftment without ATG (in unrelated donors)

  5. Evaluate relapse without ATG (in siblings) - 1 year [ Time Frame: 1 year post transplant ]
    Percent of subjects who relapsed without ATG (in siblings)

  6. Evaluate relapse without ATG (in siblings) - 2 years [ Time Frame: 2 years post transplant ]
    Percent of subjects who relapsed without ATG (in siblings)

  7. Evaluate relapse with ATG (in unrelated donors) - 1 year [ Time Frame: 1 year post transplant ]
    Percent of subjects who relapsed with ATG (in unrelated donors)

  8. Evaluate relapse with ATG (in unrelated donors) - 2 years [ Time Frame: 2 years post transplant ]
    Percent of subjects who relapsed with ATG (in unrelated donors)

  9. Evaluate relapse without ATG (in unrelated donors) - 1 year [ Time Frame: 1 year post transplant ]
    Percent of subjects who relapsed without ATG (in unrelated donors)

  10. Evaluate relapse without ATG (in unrelated donors) - 2 years [ Time Frame: 2 years post transplant ]
    Percent of subjects who relapsed without ATG (in unrelated donors)

  11. Overall survival [ Time Frame: Day 100 post transplant ]
    Percent of surviving subjects

  12. Overall survival [ Time Frame: 1 year post transplant ]
    Percent of surviving subjects

  13. Overall survival [ Time Frame: 3 years post transplant ]
    Percent of surviving subjects

  14. Transplant related mortality (TRM) [ Time Frame: Day 100 post transplant ]
    Percent of subjects with TRM

  15. Transplant related mortality (TRM) [ Time Frame: 1 year post transplant ]
    Percent of subjects with TRM



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age, Performance Status, and Graft Criteria

    • Age 0 to 70 years of age with Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years) - refer to appendix III
    • Patients ≥ 70 and ≤ 75 years of age may be eligible if they have a HCT-CI Co-Morbidity score ≤ 2 - refer to appendix II
    • Must be ≥ 3 months after prior myeloablative transplant, if applicable
    • 5/6 or 6/6 related donor match or a 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated donor marrow and/or PBSC donor match per current institutional guidelines Related donors will be evaluated and collected per MT2012-14C; Unrelated donors will be identified and collected per usual procedures
  • Eligible Diseases

    • Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia, FLT-3 ITD +; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
    • 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 Lymphocytic Leukemia (ALL): factor that define high risk CR1 include but are not limited to cytogenetics demonstrating t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
    • 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 achieved 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 imatinib mesylate.
    • Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
    • Myelodysplasia (MDS) requiring transplant as defined as: 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.
    • 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 de-bulking chemotherapy before transplant.
    • Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, NK cell malignancies are eligible after initial therapy in CR1+ or PR1+.
    • Large Cell NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
    • 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.
    • Myeloproliferative Syndromes
  • Organ Function Criteria Adequate organ function is defined as:

    • Liver: AST and ALT < 5 x upper limit of normal and bilirubin < 3 x upper limit of normal
    • Renal: Creatinine ≤ 2.0 mg/dl (adults) and estimated glomerular filtration rate (GFR) ≥ 40 mL/min (pediatrics). Adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have estimated glomerular filtration rate (GFR) > 40 mL/min.
    • Albumin > 2.5 g/dL
    • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 35%.
    • Pulmonary: DLCOcorr ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with or without exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
  • If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease
  • Females of child bearing potential and sexually active males 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 blood test or urine study within 14 days prior to registration to rule out pregnancy.
  • Untreated active infection
  • Active CNS disease
  • Active HIV infection or known HIV positive serology
  • Congenital bone marrow failure syndrome
  • Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of TBI
  • CML in refractory blast crisis
  • Intermediate or high grade NHL, mantle cell NHL, and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
  • Multiple myeloma progressive on salvage chemotherapy

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): NCT02661035


Contacts
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Contact: Timothy Krepski 612-273-2800 tkrepsk1@fairview.org

Locations
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United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Tim Krepski    612-273-2800    tkrepsk1@fairview.org   
Principal Investigator: Erica Warlick, MD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Erica Warlick, MD Masonic Cancer Center, University of Minnesota

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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT02661035     History of Changes
Other Study ID Numbers: 2015LS152
First Posted: January 21, 2016    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Masonic Cancer Center, University of Minnesota:
AML
ALL
CML
MDS
CLL
SLL
NHL
Additional relevant MeSH terms:
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Epstein-Barr Virus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Burkitt Lymphoma
Lymphoma
Leukemia
Multiple Myeloma
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myeloid
Lymphoma, Mantle-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Prolymphocytic
Waldenstrom Macroglobulinemia
Leukemia, Plasma Cell
Myelodysplastic Syndromes
Hematologic Diseases
Syndrome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Neoplasms, Plasma Cell