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Low Intensity Non-Myeloablative Preparative Conditioning Followed by Transplantation of Genetically Modified HLA-Matched Peripheral Blood Hematopoietic Precursor Cells (PBPC) for Hematologic Malignancies in HIV Positive Adults

Phase 1
Not Enrolling
Hematologic Neoplasm, HIV Infection

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Trial Information

Low Intensity Non-Myeloablative Preparative Conditioning Followed by Transplantation of Genetically Modified HLA-Matched Peripheral Blood Hematopoietic Precursor Cells (PBPC) for Hematologic Malignancies in HIV Positive Adults

Adult patients with myelodysplasia, leukemia, and non-Hodgkin's lymphoma can be cured by
allogeneic bone marrow transplantation (BMT). This curative effect has until now been
ascribed to the intense chemoradiotherapy used to condition the recipient for
transplantation. The assumption that the curative effect of allogeneic transplantation
rests in the ability to deliver very high doses of chemoradiotherapy has led to the
restriction of allogeneic transplantation to those recipient patients whose overall status
would permit the use of such intense conditioning. As a result, HIV positivity has
generally appeared as an exclusion criteria to allogeneic transplantation for hematologic
malignancies. Additionally, early studies of allogeneic BMT in HIV patients suggested no
benefit in controlling the progression to AIDS.

Several in vitro studies have demonstrated the existence of donor derived CD4 and CD8
positive lymphocytes with specific reactivity to recipient leukemia providing a potent graft
versus leukemia (GVL) effect, and this GVL effect is area of intense interest both at the
NIH and elsewhere. In fact, early attempts to decrease treatment related mortality in
chronic myelogenous leukemia (CML) patients undergoing allogeneic BMT by T-cell depletion of
the graft resulted in an unacceptably high rate of relapse suggesting that alloreactivity in
the donor graft accounted for a significant portion of the cure rate in this disease. This
GVL effect is most dramatically demonstrated among relapsed allogeneic bone marrow
transplant recipients transplanted for CML in whom a simple infusion of donor lymphocytes
can induce a complete and durable remission.

Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being
investigated for engraftment efficacy and toxicity in a number of transplant centers.
Preliminary data including our own experience with 13 patients undergoing this type of
procedure have shown a high rate of complete donor engraftment, low toxicity, and
preservation of the GVL effect. Two recent published studies investigating
non-myeloablative allo-transplantation in standard risk patients revealed an extremely low
rate of transplant related complications and mortality.

The decreased risk of transplant related complications associated with non-myeloablative
transplants expands the eligibility of transplant candidates and may allow successful
application in patients infected with HIV. In this study, we will assess the safety and
efficacy of nonmyeloablative transplantation in patients with HIV infection. Moreover, the
introduction of an HIV resistance vector into a portion of the allogeneic graft provides a
unique opportunity to test the in vivo efficacy of introducing resistance to HIV through the
self renewing stem cell.

The end points of this study are engraftment, degree of donor-host chimerism, incidence of
acute and chronic GVHD, transplant related morbidity and mortality, disease free survival,
as well as overall survival, and overall level and persistence of progeny of gene modified

Inclusion Criteria


Patients with hematologic malignancies curable by allogeneic BMT not currently considered
for transplant because of HIV positivity.

Chronic myelogenous leukemia (CML): chronic phase.

Acute lymphoblastic leukemia (ALL), all patients in complete or partial remission.

Acute myelogenous leukemia (AML): AML in first complete or partial remission.
(Exceptions: AML with good risk karyotypes: AML M3t, AML M4Eo, AML t. All AML in second
or subsequent complete remission.)

Myelodysplastic syndromes: refractory anemia (failing ATG and/or CSA) to early
transformation to acute leukemia. Chronic myelomonocytic leukemia and myeloproliferative

Chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia, in complete or partial
remission, Mantle cell lymphoma, relapsed Hodgkin's and non-Hodgkin's lymphoma.

Multiple myeloma in remission following chemotherapy.

No major organ dysfunction precluding transplantation.

DLCO greater than 40 percent predicted.

Left ventricular ejection fraction greater than 30 percent.

ECOG performance status of 0 to 2.


HLA identical sibling donor.

Fit to receive G-CSF and give peripheral blood stem cells (normal blood count,
normotensive, no history of stroke, no history of severe heart disease).

Informed consent given.


Must not be pregnant or lactating.

Must be between 18 and 80 years of age.

Must not have ECOG performance status of 3 or more. Must not have psychiatric disorder or
mental deficiency of the patient or the donor sufficiently severe as to make compliance
with the BMT treatment unlikely, and making informed consent impossible.

Must not have a major anticipated illness or organ failure incompatible with survival from
BMT as determined by your NIH physician (including encephalopathy, cardiomyopathy, and

Must not have DLCO less than 40 percent predicted.

Must not have glomerular filtration rate less than 40.

Must not have serum bilirubin greater than 4 mg/dl, transaminases greater than 4x upper
limit of normal.

Donor must be HIV negative. Donors who are positive for HBV, HCV or HTLV will be used at
the discretion of the investigator.

Must not have other malignant diseases liable to relapse or progress within 5 years.

Donor must be fit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension,
history of congestive heart failure or unstable angina, thrombocytopenia).

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

September 1999

Completion Date:

November 2001

Related Keywords:

  • Hematologic Neoplasm
  • HIV Infection
  • Peripheral Blood Stem Cells
  • Engraftment
  • Graft vs. Host Disease
  • Graft-Versus-Leukemia
  • Donor Apheresis
  • Cyclophosphamide
  • Fludarabine
  • HIV
  • AIDS
  • Gene Therapy
  • Chronic Myelogenous Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myelogenous Leukemia
  • Chronic Lymphocytic Leukemia
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Neoplasms
  • Hematologic Neoplasms



National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Bethesda, Maryland  20892