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Reduced Intensity Haploidentical Transplant for Hematological Malignancies

Primary Purpose

Hematological Malignancies

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Haploidentical Allogeneic Transplantation

About this trial

This is an interventional treatment trial for Hematological Malignancies focused on measuring Reduced Intensity Haploidentical Transplant

Eligibility Criteria

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

Inclusion Criteria:

Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied.
Patients must have a related donor who is a two or more allele mismatch at the HLA-A;B; C; DR loci.
Patients who have sibling donors with a one antigen mismatch due to recombination will not be enrolled in this protocol.
Patients must adequate organ function:
1. LVEF of >45%
2. DLCO >45% of predicted corrected for hemoglobin
3. Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal
4. Serum creatinine < 2.0 mg/dl or creatinine clearance of > 40 ml/min
Performance status > 70% (Karnofsky)
Patients must be willing to use contraception if they have childbearing potential
Able to give informed consent

Exclusion Criteria:

Performance status of < 70% (Karnofsky)
HIV positive
Active involvement of the central nervous system with malignancy
Psychiatric disorder that would preclude patients from signing an informed consent
Pregnancy
Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder or complications there from.
Patients who have received alemtuzumab within 8 weeks of transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have ATG levels of > 2 µgm/ml.
Patients who cannot receive cyclophosphamide
Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

Sites / Locations

Thomas Jefferson University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Transplantation

Arm Description

Outcomes

Primary Outcome Measures

Overall Survival at 6 Months Post-transplant in Patients Receiving a Partially-matched Related Donor Allogeneic Transplant After Reduced-intensity Conditioning

Number of patients alive at 6 months post-transplant

Secondary Outcome Measures

Number of Participants With Successful Engraftment

Immune Reconstitution

Full Information

NCT ID

NCT01162096

First Posted

July 12, 2010

Last Updated

January 3, 2018

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

1. Study Identification

Unique Protocol Identification Number

NCT01162096

Brief Title

Reduced Intensity Haploidentical Transplant for Hematological Malignancies

Official Title

A Two Step Approach To Non-Myeloablative Matched-Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies

Study Type

Interventional

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Completed

Study Start Date

September 2006 (undefined)

Primary Completion Date

September 2010 (Actual)

Study Completion Date

April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Many patients with hematological malignancies (leukemia, lymphoma, multiple myeloma) cannot undergo hematopoietic stem cell transplantation (HSCT) because they do not have a well matched donor. HSCT from partially matched family donors (haploidentical HSCT) is an option for most patients but has been associated with poor outcomes. This study was designed to test whether using an exact amount of a donor's lymphocytes (white cells) and dividing the transplant process into 2 steps, would increase overall survival by decreasing complications. The therapy is reduced intensity so it is targeted, but not limited to, patients over the age of 65 or those who have had previous transplants.

Detailed Description

Haploidentical hematopoietic stem cell transplant is a life saving therapy for patients who are without well matched donors. This type of therapy has been associated with poor outcomes in the past due to complications such as infection. The Jefferson 2 Step approach was designed to allow the infusion of an exact dose of tolerized lymphocytes in haploidentical transplant in order to allow for immune reconstitution post transplant to avoid infectious complications while still having acceptable rates of GVHD. In this approach, older patients or patients who were transplanted previously with high-risk hematological malignancies undergo chemotherapy with fludarabine and cytarabine or thiotepa. The patients then receive an exact dose of their donors' lymphocytes. The phase I portion of the study determined the optimal dose of lymphocytes. Two days after receiving the donor lymphocytes, the patients receive 2 daily doses of cyclophosphamide. The purpose of the cyclophosphamide is for in-vivo tolerization of the lymphocytes. One day after receiving cyclophosphamide, the patients receive stem cell from their donor. Tacrolimus and mycophenolate mofetil are used as GVHD prophylaxis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematological Malignancies

Keywords

Reduced Intensity Haploidentical Transplant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Transplantation

Arm Type

Experimental

Intervention Type

Device

Intervention Name(s)

Haploidentical Allogeneic Transplantation

Other Intervention Name(s)

CliniMACS

Intervention Description

Patients undergoing reduced intensity haploidentical hematopoietic stem cell transplant from a partially matched related donor.

Primary Outcome Measure Information:

Title

Overall Survival at 6 Months Post-transplant in Patients Receiving a Partially-matched Related Donor Allogeneic Transplant After Reduced-intensity Conditioning

Description

Number of patients alive at 6 months post-transplant

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Number of Participants With Successful Engraftment

Time Frame

6 months

Title

Immune Reconstitution

Time Frame

Up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients must have a related donor who is a two or more allele mismatch at the HLA-A;B; C; DR loci. Patients who have sibling donors with a one antigen mismatch due to recombination will not be enrolled in this protocol. Patients must adequate organ function: LVEF of >45% DLCO >45% of predicted corrected for hemoglobin Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal Serum creatinine < 2.0 mg/dl or creatinine clearance of > 40 ml/min Performance status > 70% (Karnofsky) Patients must be willing to use contraception if they have childbearing potential Able to give informed consent Exclusion Criteria: Performance status of < 70% (Karnofsky) HIV positive Active involvement of the central nervous system with malignancy Psychiatric disorder that would preclude patients from signing an informed consent Pregnancy Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder or complications there from. Patients who have received alemtuzumab within 8 weeks of transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have ATG levels of > 2 µgm/ml. Patients who cannot receive cyclophosphamide Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Neal Flomenberg, MD

Organizational Affiliation

Thomas Jefferson University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Thomas Jefferson University

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.JeffersonHospital.org

Description

Thomas Jefferson University Hospitals

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Reduced Intensity Haploidentical Transplant for Hematological Malignancies

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