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Reduced Intensity Conditioning Transplant Using Haploidentical Donors

Primary Purpose

Chronic Myelogenous Leukemia, Acute Myelogenous Leukemia, Myelodysplastic Syndrome

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Melphalan
Cyclophosphamide
peripheral blood stem cell transplant
Sponsored by
Northside Hospital, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myelogenous Leukemia focused on measuring CML, AML, MDS, ALL, CLL/CPL, HD, NHL, MPS, CMML, MM

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • No available matched related or unrelated donor, OR a matched related or unrelated donor will not be available in time frame necessary to perform potentially curative transplant
  • Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor (donor must have negative HLA cross-match in host vs. graft direction)
  • Karnofsky status ≥70%

  • One of the following high-risk malignancies:

    1. Chronic Myelogenous Leukemia: Chronic myelogenous leukemia in chronic phase, resistant or intolerant to available tyrosine kinase inhibitors; Chronic myelogenous leukemia in accelerated phase; Chronic myelogenous leukemia with blast crisis that has entered into a second chronic phase following induction chemotherapy
    2. Acute Myelogenous Leukemia in first or greater remission
    3. Myelodysplastic Syndrome at least one of the following: treatment-related; monosmy 7, complex cytogenetics or other high risk karyotype; IPSS score of 1.0 or greater; neutropenia or cytopenia requiring transfusion not responding to therapy; peripheral or BM blast count of <10%; CMML
    4. Acute lymphocytic leukemia/lymphoblastic lymphoma: 2nd or subsequent complete remission; first complete remission; marrow blasts <5%, but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
    5. Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia: previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs
    6. Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse): previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation
    7. Myeloproliferative diseases (myelofibrosis, CMML)
    8. Multiple Myeloma with relapse after a prior autologous transplant or eligible for allogeneic HSCT based on other risk factors

Exclusion Criteria:

  • not be excluded on basis of sex, racial, or ethnic backgrounds
  • poor cardiac function: left ventricular ejection fraction <40%
  • poor pulmonary function: FEV1 and FVC <50% predicted
  • poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy)
  • poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 40 mL/min based on Traditional Cockcroft-Gault formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x Serum creatinine (mg/dl)
  • HIV-positive
  • prior allogeneic transplant
  • women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
  • any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up

Sites / Locations

  • Northside Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Reduced-Intensity Mismatched Transplant

Arm Description

Fludarabine, Melphalan & Post-transplant cyclophosphamide

Outcomes

Primary Outcome Measures

Graft Rejection
Measurement of donor cells vs. recipient cells

Secondary Outcome Measures

Overall Survival
Number of participants still alive 2 years after transplant
Relapse Incidence
Number of patients with disease reoccurrence at 1 and 2 years post-transplant
GVHD Incidence
The number of participants that developed graft-versus-host-disease before or at 100 days after transplant

Full Information

First Posted
October 16, 2015
Last Updated
April 5, 2023
Sponsor
Northside Hospital, Inc.
Collaborators
Blood and Marrow Transplant Group of Georgia
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1. Study Identification

Unique Protocol Identification Number
NCT02581007
Brief Title
Reduced Intensity Conditioning Transplant Using Haploidentical Donors
Official Title
Reduced Intensity Conditioning and Transplantation of Partially HLA-Mismatched Peripheral Blood Stem Cells for Patients With Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
October 26, 2015 (Actual)
Primary Completion Date
November 5, 2019 (Actual)
Study Completion Date
December 28, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Northside Hospital, Inc.
Collaborators
Blood and Marrow Transplant Group of Georgia

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This trial will evaluate the safety and efficacy of a reduced intensity allogeneic HSCT from partially HLA-mismatched first-degree relatives utilizing PBSC as the stem cell source. The primary objective of the study is to estimate the incidence of graft rejection and acute GVHD. A secondary objective will be to estimate the incidence of the relapse, NRM, OS, chronic GVHD and EFS.
Detailed Description
Patients will receive a haploidentical transpalnt using a fludarabine melphalan prepartive regimen. Patients will get cyclophosphamide on days 3 & 4 post-transplant.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelogenous Leukemia, Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Myelofibrosis, CMML, Multiple Myeloma
Keywords
CML, AML, MDS, ALL, CLL/CPL, HD, NHL, MPS, CMML, MM

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Reduced-Intensity Mismatched Transplant
Arm Type
Experimental
Arm Description
Fludarabine, Melphalan & Post-transplant cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
fludarabine (30mg/m2) given every day starting on Day -6 through Day -2;
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
melphalan (140mg/m2) given one time on Day -1.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4.
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplant
Other Intervention Name(s)
HSCT
Primary Outcome Measure Information:
Title
Graft Rejection
Description
Measurement of donor cells vs. recipient cells
Time Frame
100 days
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Number of participants still alive 2 years after transplant
Time Frame
2 years
Title
Relapse Incidence
Description
Number of patients with disease reoccurrence at 1 and 2 years post-transplant
Time Frame
2 years
Title
GVHD Incidence
Description
The number of participants that developed graft-versus-host-disease before or at 100 days after transplant
Time Frame
100 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: No available matched related or unrelated donor, OR a matched related or unrelated donor will not be available in time frame necessary to perform potentially curative transplant Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor (donor must have negative HLA cross-match in host vs. graft direction) Karnofsky status ≥70% One of the following high-risk malignancies: Chronic Myelogenous Leukemia: Chronic myelogenous leukemia in chronic phase, resistant or intolerant to available tyrosine kinase inhibitors; Chronic myelogenous leukemia in accelerated phase; Chronic myelogenous leukemia with blast crisis that has entered into a second chronic phase following induction chemotherapy Acute Myelogenous Leukemia in first or greater remission Myelodysplastic Syndrome at least one of the following: treatment-related; monosmy 7, complex cytogenetics or other high risk karyotype; IPSS score of 1.0 or greater; neutropenia or cytopenia requiring transfusion not responding to therapy; peripheral or BM blast count of <10%; CMML Acute lymphocytic leukemia/lymphoblastic lymphoma: 2nd or subsequent complete remission; first complete remission; marrow blasts <5%, but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia: previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse): previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation Myeloproliferative diseases (myelofibrosis, CMML) Multiple Myeloma with relapse after a prior autologous transplant or eligible for allogeneic HSCT based on other risk factors Exclusion Criteria: not be excluded on basis of sex, racial, or ethnic backgrounds poor cardiac function: left ventricular ejection fraction <40% poor pulmonary function: FEV1 and FVC <50% predicted poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy) poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 40 mL/min based on Traditional Cockcroft-Gault formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x Serum creatinine (mg/dl) HIV-positive prior allogeneic transplant women of childbearing potential who currently are pregnant or who are not practicing adequate contraception any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melhem Solh, MD
Organizational Affiliation
Northside Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northside Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
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Citation
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Results Reference
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Reduced Intensity Conditioning Transplant Using Haploidentical Donors

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