Know Cancer

or
forgot password

Peripheral Blood Stem Cell Allotransplantation For Hematological Malignancies Using Ex Vivo CD34 Selection - a Platform For Adoptive Cellular Therapies


Phase 1/Phase 2
2 Years
80 Years
Open (Enrolling)
Both
MDS (Myelodysplastic Syndrome), Myeloproliferative Disorder, Lymphoma, Non-Hodgkin, ALL (Acute B-Lymphoblastic Leukemia), AML (Acute Meylogenous Leukemia

Thank you

Trial Information

Peripheral Blood Stem Cell Allotransplantation For Hematological Malignancies Using Ex Vivo CD34 Selection - a Platform For Adoptive Cellular Therapies


Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on
transplant techniques designed to decrease graft versus host disease (GVHD), increase the
graft-versus-leukemia (GVL) effect and reduce the risk of post-transplant graft rejection.

Through incremental transplant clinical trials we have shown that by controlling the stem
cell (CD34+ cell) and T lymphocyte (CD3+ cell) dose, severe GVHD can be reduced whilst
beneficial GVL effects can be preserved. We found that T cell depleted transplants using the
Nexell/Baxter Isolex 300i system and subsequently, the Miltenyi CliniMACS[registered] CD34+
system to obtain high CD34+ doses depleted of lymphocytes were safe to administer and
associated with less severe acute GVHD and promising response rates and overall survival.
Our previous trials have helped us to create the transplant environment (significant
lymphodepletion and minimal post transplant immunosuppression) that make for an ideal
platform for adoptive cellular immunotherapy. Adoptive cell transfer is the passive transfer
of immune cells, into a new recipient host with the goal of transferring the immunologic
functionality and characteristics into the new host.

This protocol is designed to evaluate the safety and efficacy of the Miltenyi
CliniMACS[registered] CD 34 selection system in HLA-matched sibling allogeneic peripheral
blood stem cell transplant. The manipulation of the graft is the primary research
intervention, subject to IDE# 13058, and all other aspects of clinical management on this
protocol are standard care. The target CD34+ dose range will be > 3 x 10(6)/kg and the
target CD3+ dose range will be 5 x 10(4)/kg to 1 x 10(6)/kg. Once we demonstrate adequacy of
this platform for engraftment and absence of significant GVHD in ten consecutive recipients,
we will seek IRB permission to proceed with planned adoptive cellular therapies.

The protocol will accrue up to 96 transplant recipients aged 10-75 with a hematological
malignancy and their HLA-matched sibling donors, in whom allogeneic stem cell
transplantation from an HLA-matched sibling would be routinely indicated. Diagnostic
categories will include acute and chronic leukemia, myelodysplastic syndromes, lymphomas,
multiple myeloma and myeloproliferative syndromes.

Subjects will receive a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg
total), fludarabine (125 mg/m(2) total) and total body irradiation (1200 cGy with lung
shielding to 600 cGy), followed by an infusion of a stem cell product selected for CD34+
progenitors using the Miltenyi CliniMACS[registered] system. Older subjects will receive a
lower dose of irradiation (600 cGy) without lung shielding to reduce the regimen intensity.

The overall objective is to assess the feasibility of using this system as a platform for
cellular immunotherapy initiatives. The primary study endpoint will be overall survival at
day +200. Stopping criteria for safety will monitor non-relapse mortality at day +200 and
late disease free survival at 2 years. Secondary endpoints will be standard transplant
outcome variables such as non-hematologic toxicity, incidence and severity of acute and
chronic GVHD and relapse of disease.

Inclusion Criteria


- INCLUSION CRITERIA RECIPIENT

5.1.1 Ages 10-75 years inclusive

5.1.2 Any one of the following hematologic conditions meeting a standard indication for
allogeneic stem cell transplant:

5.1.2.1 Chronic myelogenous leukemia (CML): Subjects under the age of 21 in chronic phase
OR Subjects ages 10-75 in chronic phase who have failed treatment with imatinib or have
intolerance to imatinib OR Subjects ages 10-75 in accelerated phase or blast
transformation. OR

5.1.2.2 Acute lymphoblastic leukemia (ALL): any of these categories: Adult ALL including
standard risk; Pediatric ALL in first remission with high-risk features (presenting
leukocyte count > 100,000/cu mm, karyotypes t(9; 22), t4, t19, t11, biphenotypic
leukemia). All second or subsequent remissions, primary induction failure, partially
responding or untreated relapse. OR

5.1.2.3 Acute myelogenous leukemia (AML): AML in first remission - except AML with good
risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), c-kit unmutated AML t (8; 21). All
AML in second or subsequent remission, primary induction failure and resistant relapse. OR

5.1.2.4 Myelodysplastic syndromes(MDS): any of these categories - refractory anemia with
transfusion dependence, refractory anemia with ANC< 500/microL, refractory anemia with
excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia,
atypical MDS/myeloproliferative syndromes. OR

5.1.2.5 Myeloproliferative disorders including atypical (Ph-negative) chronic myeloid and
neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential
thrombocythemia either in transformation to acute leukemia or with progressive transfusion
requirements or pancytopenia. OR

5.1.2.6 Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky
progressive disease or with thrombocytopenia (less than or equal to 100,000 / microl) or
anemia (less than or equal to 10g/dl) not due to recent chemotherapy. OR

5.1.2.7 Non-Hodgkin's lymphoma including Mantle cell lymphoma relapsing or refractory to
standard of care treatments. OR

5.1.2.8 Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed
following standard of care treatments. OR

5.1.2.9 Hodgkin's Lymphoma relapsing following an autologous transplant.

5.1.3 HLA identical (6/6) related donor.

5.1.4 For adults: ability to comprehend the investigational nature of the study and
provide informed consent. For minors: written informed consent from one parent or
guardian. Informed oral assent from minors: the process will be explained to the minor on
a level of complexity appropriate for their age and ability to comprehend.

EXCLUSION CRITERIA RECIPIENT

5.2.1 Major anticipated illness or organ failure incompatible with survival from
transplant

5.2.2 Severe psychiatric illness or mental deficiency sufficiently severe as to make
compliance with the transplant treatment unlikely and making informed consent impossible.

5.2.3 Positive pregnancy test for women of childbearing age

5.2.4 DLCO adjusted for Hb and ventilation< 50% predicted

5.2.5 Left ventricular ejection fraction < 40% (evaluated by ECHO) or < 30% (evaluated
by MUGA)

5.2.6 AST/SGOT > 10 times ULN

5.2.7 Total bilirubin > 5 times ULN

5.2.8 Estimated GFR < 15 mL/min

5.2.9 Prior allogeneic stem cell transplantation

INCLUSION CRITERIA DONOR

5.3.1 Related donor, HLA identical (6/6) with recipient

5.3.2 Weight greater than or equal to 18 kg

5.3.3 Age greater than or equal to 2 or less than or equal to 80 years old

5.3.4 For adults: ability to comprehend the investigational nature of the study and
provide informed consent. For minors: written informed consent from one parent or guardian
and informed assent: The process will be explained to the minor on a level of complexity
appropriate for their age and ability to comprehend.

EXCLUSION CRITERIA DONOR

5.4.1 Pregnant or breast-feeding. Lactating donors are permitted provided breast milk is
discarded during the days filgrastim (G-CSF) is given

5.4.2 Unfit to receive G-CSF and undergo apheresis (abnormal blood counts, history of
stroke, uncontrolled hypertension)

5.4.3 Sickling hemoglobinopathy including HbSS, HbSC

5.4.4 Donors who are positive for HIV, active hepatitis B (HBV), hepatitis C (HCV) or
human Tcell lymphotropic virus (HTLV-I/II)

5.4.5 Severe psychiatric illness or mental deficiency sufficiently severe as to make
compliance with the donation process unlikely, and making informed consent impossible.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary outcome of this protocol is to determine the rate of overall survival at 200 day using the Miltenyi CliniMACS CD34 selection system.

Outcome Time Frame:

200 days

Safety Issue:

Yes

Principal Investigator

Minocher M Battiwalla, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Heart, Lung, and Blood Institute (NHLBI)

Authority:

United States: Federal Government

Study ID:

130144

NCT ID:

NCT01866839

Start Date:

May 2013

Completion Date:

February 2017

Related Keywords:

  • MDS (Myelodysplastic Syndrome)
  • Myeloproliferative Disorder
  • Lymphoma, Non-Hodgkin
  • ALL (Acute B-Lymphoblastic Leukemia)
  • AML (Acute Meylogenous Leukemia
  • Acute Lymphoblastic Leukemia (ALL)
  • Acute Myelogenous Leukemia (AML)
  • Chronic Lymphocytic Leukemia (CLL)
  • Chronic Myelogenous Leukemia (CML)
  • Myelodyplastic Syndrome (MDS)
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892