This trial is active, not recruiting.

Conditions acute myeloid leukemia, myelodysplastic syndromes, biphenotypic leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, plasma cell neoplasms, lymphoma, hodgkin's disease, aplastic anemia
Treatments total body irradiation (tbi), donor lymphocyte infusion (dli), cyclophosphamide, mycophenolate mofetil (mmf), tacrolimus, hematopoietic stem cell transplantation (hsct)
Phase phase 2
Sponsor Thomas Jefferson University
Start date July 2010
End date May 2013
Trial size 28 participants
Trial identifier NCT01350245, 10D.219, 2010-10


The primary hypothesis of this research study is that patients in remission undergoing myeloablative haploidentical hematopoietic stem cell transplantation (HSCT) on the Thomas Jefferson University (TJU) 2 Step treatment regimen will have a disease-free survival (DFS) rate at 1 year that is the same or better than the historical DFS of patients with similar diagnoses and ages undergoing matched sibling HSCT. Based on a review of the literature a DFS rate of 50% or better at 1 year would meet the criterion for an effective alternative therapy. A DFS rate of 75% or better would imply superior efficacy of the TJU 2 Step approach over T-replete matched sibling HSCT.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
All patients treated on this trial will have hematological malignancies that are in remission at the time of the transplant. Their diseases would be expected to relapse with standard therapy alone.
total body irradiation (tbi)
Total body irradiation is given in 8 fractions over 4 days (total dose of 12 Gy).
donor lymphocyte infusion (dli)
After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days.
cyclophosphamide Endoxan
Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days
mycophenolate mofetil (mmf) CellCept
Started the day before the transplant to prevent graft versus host disease (GVHD)
tacrolimus FK-506
Started the day before the transplant to prevent graft-versus-host disease (GVHD)
hematopoietic stem cell transplantation (hsct) CliniMACS
One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-donor stem cell product. This is the day of transplant. The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem and progenitor cells in human allogeneic hematopoietic stem cell transplantation.

Primary Outcomes

Disease-Free Survival (DFS)
time frame: 1 year post-transplant

Secondary Outcomes

Time to Disease Progression
time frame: 1 year post-transplant

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Any patient with a hematologic or oncologic diagnosis without morphological evidence of disease in which allogeneic HSCT is thought to be beneficial. - Diagnoses include: Acute Myeloid Leukemia Myelodysplastic Syndromes Biphenotypic Leukemia Acute Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Lymphocytic Leukemia Plasma Cell Neoplasms Lymphoma Hodgkin Disease Aplastic Anemia 2. Patients must have a related donor who is a two or more allele mismatch at the HLA-A; B; C; DR loci. 3. Patients must adequate organ function: - LVEF of > or = 50% - DLCO > or = 50% of predicted corrected for hemoglobin - Adequate liver function as defined by a serum bilirubin < or = 1.8, AST or ALT < or = 2.5X upper limit of normal - Creatinine clearance of > or = 60 ml/min 4. Performance status > or = 70% (TJU Karnofsky) 5. HCT-CI Score < 5 Points 6. Patients must be willing to use contraception if they have childbearing potential 7. Able to give informed consent Exclusion Criteria: 1. Performance status < or = 70% (TJU Karnofsky) 2. HCT-CI Score > 5 Points 3. Combination of Performance status of < 80% (TJU Karnofsky) and an HCT-CI of 4 points or more. 4. HIV positive 5. Active involvement of the central nervous system with malignancy 6. Psychiatric disorder that would preclude patients from signing an informed consent 7. Pregnancy 8. Patients with life expectancy of < or = 6 months for reasons other than their underlying hematologic/oncologic disorder 9. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit ant-thymocyte globulin and have an ATG level of > or = 2 ugm/ml 10. Patients who cannot receive cyclophosphamide 11. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol.

Additional Information

Official title A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies in Remission From HLA Partially-Matched Related Donors
Principal investigator Dolores Grosso, DNP, CRNP
Description The primary rationale for the development of this research study is to find out if the Thomas Jefferson University (TJU) 2 Step approach to stem cell transplant is an effective treatment for patients with blood cancers who require transplant for long-term survival but are without an available matched-sibling donor. Historically, survival rates for patients undergoing half-matched stem cell transplant have been much lower than those observed after matched sibling stem cell transplant. This may be due to the poor-risk disease features of the patients by the time they are referred for hematopoietic stem cell transplantation (HSCT). Survival post half-matched stem cell transplant has also been affected by the requirement to remove or soothe donor T cells resulting in higher rates of infection and relapse. Newer approaches to haploidentical HSCT, such as the TJU 2 Step approach, utilize cyclophosphamide (CY) to tolerize donor lymphocytes instead of removing them completely from the donor product. This has resulted in less infection without concomitant increase in severe graft-versus-host disease (GVHD) and has increased overall survival as compared to older haploidentical treatment approaches due to decreases in regimen-related morbidity. Because of the historically low overall survival (OS) after haploidentical HSCT, it has become a procedure of last resort with most centers unwilling to consider it unless all other options are exhausted. With the recent development of regimens such as the TJU 2 Step approach which provide safe, alternative platforms for HSCT, it is now feasible, and ethically more acceptable, for patients without matched sibling donors to undergo HSCT prior to being heavily pretreated or developing resistant disease. In this setting, i.e. equivalent regimen safety profiles and more homogenous patient comparison groups, it is possible to more accurately compare antitumor effects between matched sibling donors and haploidentical donors. There is ample evidence in the literature that HLA mismatching causes GVHD. There is not a large body of evidence supporting the notion that HLA mismatching provides superior tumor control translating into greater relapse free survival. As compared to more common types of transplants where donor T cells are given to the recipient, the investigators would surmise that the T cell tolerization associated with the TJU 2 Step approach may decrease the anti-tumor effects of the donor immune system. Conversely, the greater degree of human leukocyte antigen (HLA) mismatch with exploitation of NK effects may mitigate some of the attenuated T cell alloreactivity. Thus, in the context of comparable regimen-related toxicity, our major aim in this research study is to compare graft versus tumor effects as measured by disease-free survival (DFS) between matched sibling HSCT and the TJU 2 Step haploidentical HSCT. If DFS is similar despite T cell tolerization, than the TJU 2 Step haploidentical approach should be considered an effective alternative therapy for those patients in remission without a matched sibling donor. The widespread benefit of this outcome would be the enfranchisement of segments of the population who are without available matched donors resulting in a delay or a failure to receive this potentially life-saving therapy. If DFS survival after treatment on the TJU 2 Step haploidentical approach is superior to what would be expected after matched sibling HSCT, then one could conclude that haploidentical HSCT confers greater tumor control forming the basis for future studies regarding the potential benefits of utilizing haploidentical donors over matched sibling donors when both types of donors are available.
Trial information was received from ClinicalTrials.gov and was last updated in July 2014.
Information provided to ClinicalTrials.gov by Thomas Jefferson University.