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Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases

Primary Purpose

Acute Leukemias, Burkitt's Lymphoma, Chronic Myelogenous Leukemia

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Cyclophosphamide
Total Body Irradiation
Haploidentical stem cell transplant
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Leukemias focused on measuring Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Burkitt's lymphoma, Natural killer cell malignancies, Chronic myelogenous leukemia, Myelodysplastic syndrome, Large-cell lymphoma, Hodgkin lymphoma, Multiple myeloma, Chronic lymphocytic leukemia (CLL), Small lymphocytic lymphoma (SLL), Marginal zone B-cell lymphoma, Follicular lymphoma, Lymphoplasmacytic lymphoma, Mantle-cell lymphoma, Prolymphocytic leukemia, Refractory leukemia, Myelodysplastic syndrome (MDS), Bone marrow failure syndromes, Myeloproliferative syndromes

Eligibility Criteria

undefined - 74 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Must be <75 years old with no 7/8 or 8/8 HLA-matched sibling donor
  • One or more potential related mismatched donors (e.g. biologic parent (s) or siblings (full or half) or children). Low resolution using DNA based typing at HLA-A, -B and -DRB1 for potential haploidentical donors is required.
  • 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 Lymphoblastic Leukemia (ALL) in first complete remission (CR1) that is NOT considered favorable-risk.
    • Acute Myelogenous Leukemia (AML) in first complete remission (CR1) that is NOT considered as favorable-risk.
    • Acute Leukemias in 2nd or subsequent CR
    • Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent CR
    • Burkitt's lymphoma in CR2 or subsequent CR
    • Natural killer cell malignancies after response to initial therapy
    • Chronic myelogenous leukemia: all types except refractory blast crisis.
    • Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease that has failed or patients who are ineligible for an autologous transplant.
    • 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.
    • Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive.
    • Refractory leukemia or MDS These patients may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody.
    • Bone marrow failure syndromes, except for Fanconi Anemia
    • Myeloproliferative syndromes
  • Adequate organ function is defined as:

    • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 35%. For children that are not able to cooperate with multigated acquisition scan (MUGA) and echocardiography, such should be clearly stated in the physician's note
    • Pulmonary: Diffusing capacity of lung for carbon monoxide (DLCO) > 30% predicted, and absence of O2 requirements. For children that are not able to cooperate with pulmonary function tests (PFTs), a pulse oximetry with exercise should be attempted. If nether test can be obtained it should be clearly stated in the physician's note.
    • Liver: Transaminases < 5 x upper limit of normal and bilirubin < 3 x upper limit of normal
    • Renal: serum creatinine < 2.0 mg/dl (adults) or glomerular filtration rate (GFR) >40 mL/min/1.73m2 (peds). Patients with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have glomerular filtration rate (GFR) > 40 mL/min/1.73m2.
    • Adequate performance status is defined as Karnofsky score ≥ 60% (> 16 years of age) or Lansky score ≥ 50 (pediatrics)
  • If recent mold infection e.g. Aspergillus - must have minimum of 30 days of appropriate treatment before bone marrow transplant (BMT) and infection controlled and be cleared by Infectious Disease.
  • Second BMT: Must be > 3 months after prior myeloablative transplant.
  • Patients must be ineligible for autologous transplantation due to prior autologous transplant, an inadequate autologous stem cell harvest, inability to withstand a myeloablative preparative regimen, or clinically aggressive/high risk disease.
  • Patients are eligible for transplantation if there is no 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.
  • Patients with stable disease are eligible for transplantation if the largest residual nodal mass is < 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately).
  • Voluntary written consent (adult or parental/guardian)

Exclusion Criteria:

  • Available and clinically suitable 5-6/6 HLA-A, B, DRB1 matched sibling donor
  • Pregnant or breastfeeding
  • Evidence of HIV infection or known HIV positive serology
  • Current active serious infection
  • Unless in post-chemotherapy and radioimmunoconjugated antibody induced aplasia, when he/she would be eligible, patients with acute leukemia in morphologic relapse/ persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible.
  • Chronic myeloid leukemia (CML) in refractory blast crisis
  • Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
  • active central nervous system malignancy

Sites / Locations

  • University of Minnesota Masonic Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Haploidentical stem cell transplant

Arm Description

This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI).

Outcomes

Primary Outcome Measures

2 Year Survival
Percentage of patients that survive 2 years post-transplant

Secondary Outcome Measures

Number of Patients With Hematopoietic Engraftment
Engraftment is defined as absolute neutrophil count (ANC) ≥ 5 X 10^8/L for 3 consecutive measurements.
Number of Patients With Chimerism
Number of patients with chimerism at day 100, 6 months and 1 year
Number of Patients Experiencing Acute Graft-versus-host Disease by 100 Days
Number of Patients Experiencing Chronic Graft-versus-host Disease by 1 Year
Number of Patients Experiencing Transplant Related Mortality (TRM)

Full Information

First Posted
May 20, 2014
Last Updated
December 12, 2019
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT02145039
Brief Title
Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases
Official Title
Reduced Intensity Conditioning (RIC) and Transplantation of HLA(Human Leukocyte Antigen)-Haploidentical Related Bone Marrow (Haplo-BM) For Patients With Hematologic Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Terminated
Why Stopped
Replaced by another study.
Study Start Date
October 2014 (Actual)
Primary Completion Date
January 2018 (Actual)
Study Completion Date
January 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen, consisting of fludarabine, cyclophosphamide and low dose total body irradiation (TBI), is designed for the treatment of patients with advanced and/or high risk diseases.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Leukemias, Burkitt's Lymphoma, Chronic Myelogenous Leukemia
Keywords
Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Burkitt's lymphoma, Natural killer cell malignancies, Chronic myelogenous leukemia, Myelodysplastic syndrome, Large-cell lymphoma, Hodgkin lymphoma, Multiple myeloma, Chronic lymphocytic leukemia (CLL), Small lymphocytic lymphoma (SLL), Marginal zone B-cell lymphoma, Follicular lymphoma, Lymphoplasmacytic lymphoma, Mantle-cell lymphoma, Prolymphocytic leukemia, Refractory leukemia, Myelodysplastic syndrome (MDS), Bone marrow failure syndromes, Myeloproliferative syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Haploidentical stem cell transplant
Arm Type
Experimental
Arm Description
This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI).
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant.
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation
Other Intervention Name(s)
TBI
Intervention Description
TBI 200cGy on day -1 before transplant.
Intervention Type
Biological
Intervention Name(s)
Haploidentical stem cell transplant
Other Intervention Name(s)
HSCT
Intervention Description
Non-T-cell depleted bone marrow infusion
Primary Outcome Measure Information:
Title
2 Year Survival
Description
Percentage of patients that survive 2 years post-transplant
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Number of Patients With Hematopoietic Engraftment
Description
Engraftment is defined as absolute neutrophil count (ANC) ≥ 5 X 10^8/L for 3 consecutive measurements.
Time Frame
42 days
Title
Number of Patients With Chimerism
Description
Number of patients with chimerism at day 100, 6 months and 1 year
Time Frame
100 days
Title
Number of Patients Experiencing Acute Graft-versus-host Disease by 100 Days
Time Frame
100 days
Title
Number of Patients Experiencing Chronic Graft-versus-host Disease by 1 Year
Time Frame
1 year
Title
Number of Patients Experiencing Transplant Related Mortality (TRM)
Time Frame
6 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must be <75 years old with no 7/8 or 8/8 HLA-matched sibling donor One or more potential related mismatched donors (e.g. biologic parent (s) or siblings (full or half) or children). Low resolution using DNA based typing at HLA-A, -B and -DRB1 for potential haploidentical donors is required. 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 Lymphoblastic Leukemia (ALL) in first complete remission (CR1) that is NOT considered favorable-risk. Acute Myelogenous Leukemia (AML) in first complete remission (CR1) that is NOT considered as favorable-risk. Acute Leukemias in 2nd or subsequent CR Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent CR Burkitt's lymphoma in CR2 or subsequent CR Natural killer cell malignancies after response to initial therapy Chronic myelogenous leukemia: all types except refractory blast crisis. Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease that has failed or patients who are ineligible for an autologous transplant. 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. Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive. Refractory leukemia or MDS These patients may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody. Bone marrow failure syndromes, except for Fanconi Anemia Myeloproliferative syndromes Adequate organ function is defined as: Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 35%. For children that are not able to cooperate with multigated acquisition scan (MUGA) and echocardiography, such should be clearly stated in the physician's note Pulmonary: Diffusing capacity of lung for carbon monoxide (DLCO) > 30% predicted, and absence of O2 requirements. For children that are not able to cooperate with pulmonary function tests (PFTs), a pulse oximetry with exercise should be attempted. If nether test can be obtained it should be clearly stated in the physician's note. Liver: Transaminases < 5 x upper limit of normal and bilirubin < 3 x upper limit of normal Renal: serum creatinine < 2.0 mg/dl (adults) or glomerular filtration rate (GFR) >40 mL/min/1.73m2 (peds). Patients with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have glomerular filtration rate (GFR) > 40 mL/min/1.73m2. Adequate performance status is defined as Karnofsky score ≥ 60% (> 16 years of age) or Lansky score ≥ 50 (pediatrics) If recent mold infection e.g. Aspergillus - must have minimum of 30 days of appropriate treatment before bone marrow transplant (BMT) and infection controlled and be cleared by Infectious Disease. Second BMT: Must be > 3 months after prior myeloablative transplant. Patients must be ineligible for autologous transplantation due to prior autologous transplant, an inadequate autologous stem cell harvest, inability to withstand a myeloablative preparative regimen, or clinically aggressive/high risk disease. Patients are eligible for transplantation if there is no 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. Patients with stable disease are eligible for transplantation if the largest residual nodal mass is < 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately). Voluntary written consent (adult or parental/guardian) Exclusion Criteria: Available and clinically suitable 5-6/6 HLA-A, B, DRB1 matched sibling donor Pregnant or breastfeeding Evidence of HIV infection or known HIV positive serology Current active serious infection Unless in post-chemotherapy and radioimmunoconjugated antibody induced aplasia, when he/she would be eligible, patients with acute leukemia in morphologic relapse/ persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible. Chronic myeloid leukemia (CML) in refractory blast crisis Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky. active central nervous system malignancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudio Brunstein, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota Masonic Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

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Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases

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