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Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

Primary Purpose

Hematologic Malignancy

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Total Body Irradiation

Donor Lymphocyte Infusion (DLI)

Cyclophosphamide

Tacrolimus

Mycophenolate mofetil

Allogeneic hematopoietic stem cell transplantation

Laboratory biomarker analysis

About this trial

This is an interventional treatment trial for Hematologic Malignancy focused on measuring allogeneic stem cell transplant, TJU 2 Step, HSCT, Hematopoietic stem cell transplantation

Eligibility Criteria

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

Inclusion Criteria:

Any patient with a hematologic malignancy with residual disease after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely or who is in 3rd or greater complete remission (CR).
Patients with marrow based diseases in which the marrow biopsy does not meet criteria for active disease (ie <5% blasts in acute leukemia) but who does not have full count recovery will be eligible for treatment on this high risk trial.
Patients must have at least one related donor who is HLA mismatched in the GVHD direction at two or more HLA loci.
Patients must adequate organ function:
1. Left ventricular ejection fraction (LVEF) of >50 %
2. Diffusion capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) >50 % of predicted
3. Adequate liver function as defined by a serum bilirubin <1.8, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times upper limit of normal
4. Creatinine clearance of > 60 ml/min
Karnofsky Performance Status of > 80% on the modified KPS tool
Patients must be willing to use contraception if they have childbearing potential.
Able to give informed consent

Exclusion Criteria:

Modified Karnofsky performance status (KPS) of <80%
> 5 Comorbidity Points on the hematopoietic cell transplantation comorbidity index (HCT-CI) Index
Untreated class I or II antibodies against donor HLA antigens
HIV positive
Active involvement of the central nervous system with malignancy
Psychiatric disorder that would preclude patients from signing an informed consent
Pregnancy, or unwillingness to use contraception if they have child bearing potential
Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
Alemtuzumab treatment within 8 weeks of HSCT admission.
Anti-thymocyte globulin (ATG) level of > 2 ugm/ml
Patients with active inflammatory processes including Tmax >101 or active tissue inflammation are excluded
Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan

Sites / Locations

Sidney Kimmel Cancer Center at Thomas Jefferson University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Allogeneic HSCT

Arm Description

CONDITIONING: Patients undergo Total Body Irradiation (TBI) twice daily (BID) on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive DLI on day -6 and undergo cluster of differentiation 34 (CD34+) selected allogeneic HSCT on day 0 GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28.

Outcomes

Primary Outcome Measures

Number of Participants That Experience One Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplant (HSCT)

To assess relapse free survival in participants undergoing Hematopoietic Stem Cell Transplant (HSCT) using the Thomas Jefferson University 2 step approach with an extra day inserted between the donor lymphocyte infusion (DLI) and administration of cyclophosphamide.

Secondary Outcome Measures

Pace of T-cell and B-cell Immune Recovery

Reported descriptively

Regimen Related Toxicities Graded According to the National Cancer Institute (NCI) Common Toxicity Criteria, Version 3.0

Reported descriptively

Incidence and Severity of GVHD, Graded According to Standard Criteria

Reported descriptively

Full Information

NCT ID

NCT01341301

First Posted

April 21, 2011

Last Updated

April 23, 2018

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

1. Study Identification

Unique Protocol Identification Number

NCT01341301

Brief Title

Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

Official Title

A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using One Human Leukocyte Antigen Partially-Matched Related Donor

Study Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Completed

Study Start Date

May 2010 (undefined)

Primary Completion Date

November 4, 2013 (Actual)

Study Completion Date

August 7, 2014 (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

The purpose of this research study is to examine the survival of patients undergoing partially matched hematopoietic stem cell transplant (HSCT) on a new type of treatment approach, which has been developed specifically for patients who have evidence of their disease at the time of transplant. In this research study, a way of strengthening the response of the donor cells against the disease has been developed. Patients will undergo one additional day between the two steps of the transplant which may allow their donor's cells to fight the disease more effectively.

Detailed Description

This is a phase II study in which patients receive a haploidentical HSCT from a single donor. The period between the donor lymphocyte infusion (DLI) and tolerizing doses of CY has been extended to allow for an increased period of allogeneic response against tumor targets. The outcomes of patients undergoing this extra time period will be compared to historical data to assess efficacy. Primary Objective: 1) To assess 1 year relapse free survival in patients undergoing hematopoietic stem cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach with an extra day inserted between the DLI and administration of cyclophosphamide (CY). Secondary Objectives: To assess the consistency and pace of engraftment. To assess the pace of T cell and B cell immune recovery. To assess regimen related toxicity, (GVHD) graft-versus-host disease incidence and severity, and overall survival in patients undergoing treatment on this protocol. . To assess the tolerance of the period of fever, diarrhea, and rash in each arm in an effort to determine whether a longer interval prior to cytoxan changes this side effect qualitatively compared to prior patient groups or concurrent patient groups. N.B. Patients with hematologic malignancies in remission will continue to be transplanted without modification to the original 2-step approach and will serve as a concurrent comparison group. To collect leukemia samples prior to transplant and after relapse whenever possible. To assess the overall degree of HLA-class I and class II expression on these paired samples. To test for loss of one or both HLA haplotypes in the relapsed tumor specimens. To determine the number of cluster of differentiation 4 (CD4+) cluster of differentiation 25 (CD25+) FOXP3+ regulatory cells post HSCT and to assess whether this is correlated with the development of GVHD after transplant.

6. Conditions and Keywords

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

Hematologic Malignancy

Keywords

allogeneic stem cell transplant, TJU 2 Step, HSCT, Hematopoietic stem cell transplantation

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

Allogeneic HSCT

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Total Body Irradiation

Other Intervention Name(s)

TBI

Intervention Description

Undergo TBI

Intervention Type

Biological

Intervention Name(s)

Donor Lymphocyte Infusion (DLI)

Other Intervention Name(s)

DLI

Intervention Description

Undergo DLI

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan, Endoxan, Endoxana, Enduxan

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

Advagraf, Prograf, Protopic

Intervention Description

Given IV or PO

Intervention Type

Drug

Intervention Name(s)

Mycophenolate mofetil

Other Intervention Name(s)

Cellcept

Intervention Description

Given IV or PO

Intervention Type

Procedure

Intervention Name(s)

Allogeneic hematopoietic stem cell transplantation

Intervention Description

Undergo allogeneic HSCT

Intervention Type

Other

Intervention Name(s)

Laboratory biomarker analysis

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

Number of Participants That Experience One Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplant (HSCT)

Description

Time Frame

1 year after undergoing hematopoietic stem cell transplant

Secondary Outcome Measure Information:

Title

Pace of T-cell and B-cell Immune Recovery

Description

Reported descriptively

Time Frame

Assessed up to 1 year

Title

Regimen Related Toxicities Graded According to the National Cancer Institute (NCI) Common Toxicity Criteria, Version 3.0

Description

Reported descriptively

Time Frame

Assessed up to 1 year

Title

Incidence and Severity of GVHD, Graded According to Standard Criteria

Description

Reported descriptively

Time Frame

Assessed up to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Any patient with a hematologic malignancy with residual disease after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely or who is in 3rd or greater complete remission (CR). Patients with marrow based diseases in which the marrow biopsy does not meet criteria for active disease (ie <5% blasts in acute leukemia) but who does not have full count recovery will be eligible for treatment on this high risk trial. Patients must have at least one related donor who is HLA mismatched in the GVHD direction at two or more HLA loci. Patients must adequate organ function: Left ventricular ejection fraction (LVEF) of >50 % Diffusion capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) >50 % of predicted Adequate liver function as defined by a serum bilirubin <1.8, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times upper limit of normal Creatinine clearance of > 60 ml/min Karnofsky Performance Status of > 80% on the modified KPS tool Patients must be willing to use contraception if they have childbearing potential. Able to give informed consent Exclusion Criteria: Modified Karnofsky performance status (KPS) of <80% > 5 Comorbidity Points on the hematopoietic cell transplantation comorbidity index (HCT-CI) Index Untreated class I or II antibodies against donor HLA antigens HIV positive Active involvement of the central nervous system with malignancy Psychiatric disorder that would preclude patients from signing an informed consent Pregnancy, or unwillingness to use contraception if they have child bearing potential Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder Alemtuzumab treatment within 8 weeks of HSCT admission. Anti-thymocyte globulin (ATG) level of > 2 ugm/ml Patients with active inflammatory processes including Tmax >101 or active tissue inflammation are excluded Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Neal Flomenberg, MD

Organizational Affiliation

Thomas Jefferson University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Dolores Grosso, DNP, CRNP

Organizational Affiliation

Thomas Jefferson University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sidney Kimmel Cancer Center at 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

Learn more about this trial

Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

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