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Allogeneic Transplantation From Related Haploidentical Donors

Primary Purpose

Blood Cancer, Leukemia, Graft Versus Host Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
non-myeloablative hematopoietic cell transplantation
Anti-Thymocyte Globulin
Cyclosporine
Mycophenolate Mofetil
G-CSF
Solumedrol
Acetaminophen
Diphenydramine
Hydrocortisone
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Blood Cancer

Eligibility Criteria

12 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥ 50 years with hematologic malignancies treatable by a mixed chimera allogeneic HCT. For patients ≤ 50 years of age with hematologic malignacies treatable with mixed chimera HCT who because of pre-exisiting medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional transplants. Indolent advanced stage NHL, CLL, HD - Must have received and failed front-line therapy. Multiple myeloma (Stage II or III) - Must have received prior chemotherapy. Consolidation after prior autografting is permitted. AML/ALL - Must be in complete hematologic remission and have received cytotoxic chemotherapy at some stage before transplant. Patients with molecular or cytogenetic relapse will be accepted providing a donor is available. Patients with persistent or refractory disease will be considered on a case by case basis and transplants must be approved by the principal investigator. CML - Patients will be accepted in chronic or accelerated phase. Patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy for either peripheral blood stem cell mobilization or treatment of advanced CML may be enrolled provided they are in CR, chronic phase or accelerated phase. MDS - All patients with MDS will be eligible for this protocol, however, those patients with >10% blasts will require chemotherapy to reduce the blast % to < 10%. SAA - Patients with severe aplastic anemia who have failed front line therapy. A fully HLA-identical sibling donor is not available. A matched unrelated donor has not been identified. A haploidentical related donor is available who is in good health and does not have contraindications to donation. Exclusion Criteria: Patients with rapidly progressive intermediate or high grade NHL Uncontrolled CNS involvement with disease Fertile men Women unwilling to use contraceptive techniques during and for 12 months following treatment Females who are pregnant Cardiac function: ejection fraction < 30% or cardiac failure requiring therapy Pulmonary: DLCO < 40% predicted and/or receiving supplementary continuous oxygen Liver function abnormalities: elevation of bilirubin to > 4 mg/dl and/or transaminases > 3x the upper limit of normal. If hyperbilirubinemai is due to a known cause that will not increase the risks of transplant, than this upper limit may be exceeded. Renal: creatinine clearance < 50 cc/min (24 hour urine collection) Karnofsky performance score < 60% Patients with poorly controlled hypertension. Documented fungal disease that persists despite treatment HIV positive patients. Hepatitis B and C positive patients will be evaluated on a case by case basis Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or principal investigator would place the patient at unacceptable risk from this regimen.

Sites / Locations

  • Stanford University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Transplantation of CD34+ cells

Arm Description

Week #1: Total Lymphoid Inrradiation (TLI) 120 cGy + Anti-thymocyte Globulin (ATG) 1.5 mg/kg + Solumedrol 1.0 mg/kg Daily for 5 days. Week #2: TLI 120 cGy (3 days a week, double on the 4th day) 5 days of CSP (oraly) one day after TLI was started. 3 days of MMF 4 days after TLI was started.

Outcomes

Primary Outcome Measures

Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning
number achieving donor cell engraftment (>95%) by day 90 after transplant.

Secondary Outcome Measures

Acute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant
GVHD grading system goes from 0-4 where grade 4 is the most severe. Grade 0 and 1 do not require systemic treatment, Grade 2-4 require treatment. This trial evaluated the risk of developing acute GVHD grades 2-4 within 90 days of transplant.

Full Information

First Posted
September 12, 2005
Last Updated
November 17, 2019
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT00185692
Brief Title
Allogeneic Transplantation From Related Haploidentical Donors
Official Title
Allogeneic Hematopoietic Cell Transplantation of Positively Selected CD34+ Cells and Defined Inoculum of T Cells From Related Haploidentical Donors for Older Patients With Indolent Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
August 2000 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of the study is to evaluate the feasibility and safety of transplanting CD34+ selected hematopoietic cells from a haploidentical related donor following a nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG).
Detailed Description
An alternative to conventional allogeneic bone marrow transplantation is by using a non-myeloablative conditioning regimen. This regime would consist of both; total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG). Used in combination to achieve engraftment of haploidentical CD34+ selected peripheral blood stem cells in older patients or patients with underlying medical conditions that preclude standard allogeneic treatment. The expected results of this transplant regime will be expected to result in hematopoietic and immunologic reconstitution, decreased deaths related to the treatment regimen and decreased gravft-vs-host disease (GVHD).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blood Cancer, Leukemia, Graft Versus Host Disease, Malignancy, CLL, NHL, Hodgkin's Disease, MDS

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Transplantation of CD34+ cells
Arm Type
Experimental
Arm Description
Week #1: Total Lymphoid Inrradiation (TLI) 120 cGy + Anti-thymocyte Globulin (ATG) 1.5 mg/kg + Solumedrol 1.0 mg/kg Daily for 5 days. Week #2: TLI 120 cGy (3 days a week, double on the 4th day) 5 days of CSP (oraly) one day after TLI was started. 3 days of MMF 4 days after TLI was started.
Intervention Type
Procedure
Intervention Name(s)
non-myeloablative hematopoietic cell transplantation
Other Intervention Name(s)
Peripheral-blood stem-cell transplantation
Intervention Description
TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil.
Intervention Type
Drug
Intervention Name(s)
Anti-Thymocyte Globulin
Other Intervention Name(s)
ATG
Intervention Description
1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes.
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Other Intervention Name(s)
INN/BAN, USAN, CSA
Intervention Description
6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin).
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
MMF, CellCept
Intervention Description
15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively which blocks the de nobo synthesis of guanosine required for DNA synthesis and has an effect on T and B cells.
Intervention Type
Drug
Intervention Name(s)
G-CSF
Other Intervention Name(s)
Granulocyte colony-stimulating factor, CSF 3
Intervention Description
16 mg/kg, SQ Growth factor used to make bone marrow produce more blood cells
Intervention Type
Drug
Intervention Name(s)
Solumedrol
Other Intervention Name(s)
6-Methylprednisolone, Methylprednisolone Acetate, Methylprednisolone Sodium Succinate
Intervention Description
1.0 mg/kg IV 2 hours prior to ATG Used to treat severe inflamation
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Other Intervention Name(s)
Tylenol
Intervention Description
650 mg PO, 30 minutes prior to infusion Pain reliever
Intervention Type
Drug
Intervention Name(s)
Diphenydramine
Other Intervention Name(s)
Benadryl, Allermax, Q-Dryl, Diphen Cough
Intervention Description
50 mg IV, 30 minutes prior to infusion Used to relieve allergy symptoms
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Other Intervention Name(s)
Hydrocortisone Sodium Phosphate
Intervention Description
100 mg IV, 1 hour prior to infusion Used to relieve itching, redness and swelling of the skin
Primary Outcome Measure Information:
Title
Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning
Description
number achieving donor cell engraftment (>95%) by day 90 after transplant.
Time Frame
100 days
Secondary Outcome Measure Information:
Title
Acute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant
Description
GVHD grading system goes from 0-4 where grade 4 is the most severe. Grade 0 and 1 do not require systemic treatment, Grade 2-4 require treatment. This trial evaluated the risk of developing acute GVHD grades 2-4 within 90 days of transplant.
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 50 years with hematologic malignancies treatable by a mixed chimera allogeneic HCT. For patients ≤ 50 years of age with hematologic malignacies treatable with mixed chimera HCT who because of pre-exisiting medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional transplants. Indolent advanced stage NHL, CLL, HD - Must have received and failed front-line therapy. Multiple myeloma (Stage II or III) - Must have received prior chemotherapy. Consolidation after prior autografting is permitted. AML/ALL - Must be in complete hematologic remission and have received cytotoxic chemotherapy at some stage before transplant. Patients with molecular or cytogenetic relapse will be accepted providing a donor is available. Patients with persistent or refractory disease will be considered on a case by case basis and transplants must be approved by the principal investigator. CML - Patients will be accepted in chronic or accelerated phase. Patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy for either peripheral blood stem cell mobilization or treatment of advanced CML may be enrolled provided they are in CR, chronic phase or accelerated phase. MDS - All patients with MDS will be eligible for this protocol, however, those patients with >10% blasts will require chemotherapy to reduce the blast % to < 10%. SAA - Patients with severe aplastic anemia who have failed front line therapy. A fully HLA-identical sibling donor is not available. A matched unrelated donor has not been identified. A haploidentical related donor is available who is in good health and does not have contraindications to donation. Exclusion Criteria: Patients with rapidly progressive intermediate or high grade NHL Uncontrolled CNS involvement with disease Fertile men Women unwilling to use contraceptive techniques during and for 12 months following treatment Females who are pregnant Cardiac function: ejection fraction < 30% or cardiac failure requiring therapy Pulmonary: DLCO < 40% predicted and/or receiving supplementary continuous oxygen Liver function abnormalities: elevation of bilirubin to > 4 mg/dl and/or transaminases > 3x the upper limit of normal. If hyperbilirubinemai is due to a known cause that will not increase the risks of transplant, than this upper limit may be exceeded. Renal: creatinine clearance < 50 cc/min (24 hour urine collection) Karnofsky performance score < 60% Patients with poorly controlled hypertension. Documented fungal disease that persists despite treatment HIV positive patients. Hepatitis B and C positive patients will be evaluated on a case by case basis Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or principal investigator would place the patient at unacceptable risk from this regimen.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Lowsky
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Allogeneic Transplantation From Related Haploidentical Donors

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