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A Reduced Intensity Conditioning Regimen With CD3-Depleted Hematopoietic Stem Cells to Improve Survival for Patients With Hematologic Malignancies Undergoing Haploidentical Stem Cell Transplantation


Phase 2
N/A
21 Years
Open (Enrolling)
Both
Leukemia, Acute Lymphocytic (ALL), Leukemia, Myeloid, Acute(AML), Leukemia, Myeloid, Chronic(CML), Juvenile Myelomonocytic Leukemia (JMML), Hemoglobinuria, Paroxysmal Nocturnal (PNH), Hodgkin Lymphoma, Lymphoma, Non-Hodgkin (NHL), Myelodysplastic Syndrome (MDS)

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Trial Information

A Reduced Intensity Conditioning Regimen With CD3-Depleted Hematopoietic Stem Cells to Improve Survival for Patients With Hematologic Malignancies Undergoing Haploidentical Stem Cell Transplantation


This study will explore the following objectives:

1. To assess if the event-free survival at one-year post-transplant for research
participants with high-risk hematologic malignancies can be improved following HAPLO
hematopoietic stem cell transplant (HSCT) using a graft depleted of CD3+ cells ex vivo
and a reduced intensity-conditioning regimen.

Secondary objectives:

1. To estimate the one-year overall survival (OS) and disease-free survival (DFS) for
research participants who receive this study treatment.

2. To estimate the cumulative incidence of relapse for research participants who receive
this study treatment.

3. To estimate the rate of overall grade III-IV acute GVHD, and the rate and severity of
chronic GVHD in research participants.

4. To estimate the incidence of non-hematologic regimen-related toxicity and
regimen-related mortality in the first 100 days post-transplant.

Exploratory objectives:

1. To explore the biologic significance of soluble interleukin-2 receptor and immunologic
state [quantitative lymphocyte studies, V beta spectratyping, T-cell receptor excision
circles (TREC) assay] to predict the development of acute and chronic GVHD in these
research participants.

2. To measure the pharmacokinetics of Campath-1H in pediatric HAPLO HSCT recipients


Inclusion Criteria:

(transplant recipient)

- Patients less than or equal to 21 years of age; may be greater than 21 years old if a
current St. Jude patient or previously treated St. Jude patient within 3 years of
completion of prior treatment.

- Must have one of the following diagnosis:

- ALL high risk in second remission. Examples include relapse on therapy, first
remission duration of less than or equal to 30 months, or relapse within 12
months of completing therapy.

- ALL in third or subsequent remission.

- ALL high risk in first remission. Examples include: induction failure, minimal
residual disease greater than or equal to 1% marrow blasts by morphology after
induction, persistent or recurrent cytogenetic or molecular evidence of disease
during therapy requiring additional therapy after induction to achieve
remission.

- High-risk AML in first remission. Examples include monosomy 7, M6, M7, t(6;9),
FLT3-ITD, or patients who have greater than or equal to 25% blasts by
morphology after induction or who do not achieve CR after 2 courses of therapy.

- Relapsed or persistent AML (less than or equal to 25% blasts in marrow by
morphology).

- AML in second or subsequent morphologic remission.

- CML in first chronic phase with detectable molecular or cytogenetic evidence of
disease despite medical therapy; or CML with a history of accelerated or blast
crisis, now in chronic phase; or unable to tolerate tyrosine kinase inhibitor
therapy.

- Juvenile myelomonocytic leukemia (JMML).

- Myelodysplastic syndrome (MDS).

- Therapy related (secondary) AML, ALL, or MDS.

- Hodgkin lymphoma in second or subsequent complete remission (CR) after prior
autologous HSCT transplant or will be unable to have hematopoietic stem cells
collected for autologous HSCT.

- Non-Hodgkin lymphoma (NHL) in second or subsequent CR after prior autologous
HSCT or unable to have stem cells collected for autologous HSCT.

- Has not received a prior allogeneic hematopoietic stem cell transplant.

- Does not have a suitable HLA-matched sibling donor available for stem cell donation.

- Does not have a suitable cord blood product or volunteer matched unrelated donor
(MUD) available in the necessary time for stem cell donation.

- Has a suitable HLA partially matched family member available for stem cell donation.

- Cardiac shortening fraction greater than or equal to 25%.

- Creatinine clearance greater than or equal to 40 ml/min/1.73 m^2.

- Forced vital capacity (FVC) greater than or equal to 40% of predicted value or a
pulse oximetry value of greater than or equal to 92% on room air.

- Direct bilirubin less than or equal to 3 mg/dl.

- Age-dependent performance score of greater than or equal to 50.

- Serum glutamic pyruvic transaminase (SGPT) less than 3 times the upper limit of
normal for age.

- Karnofsky or Lansky (age-dependent) performance score of greater than or equal to 50.

- No known allergy to murine products or human anti-mouse antibody (HAMA) results
within normal limits.

- Not pregnant (confirmed by negative serum or urine pregnancy test within 14 days
prior to enrollment).

- Not lactating.

Inclusion criteria (stem cell donor):

- Partially HLA matched family member.

- At least 18 years of age.

- Human immunodeficiency virus (HIV) negative.

- Not pregnant (confirmed by negative serum or urine pregnancy test within 7 days prior
to enrollment).

- Not lactating.

Inclusion criteria (transplant recipient - stem cell boost)

Has experienced one of the following disorders post-transplant:

- graft failure

- graft rejection

- delayed hematopoietic and/or immune reconstitution.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

To determine if one year event-free survival can be improved in pediatric patients undergoing a haploidentical transplant by using a reduced intensity conditioning regimen and a targeted dose T cell depleted donor product.

Outcome Time Frame:

one year post-transplant

Safety Issue:

Yes

Principal Investigator

Brandon Triplett, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

St. Jude Children's Research Hospital

Authority:

United States: Food and Drug Administration

Study ID:

HIFLEX

NCT ID:

NCT00566696

Start Date:

November 2007

Completion Date:

January 2018

Related Keywords:

  • Leukemia, Acute Lymphocytic (ALL)
  • Leukemia, Myeloid, Acute(AML)
  • Leukemia, Myeloid, Chronic(CML)
  • Juvenile Myelomonocytic Leukemia (JMML)
  • Hemoglobinuria, Paroxysmal Nocturnal (PNH)
  • Hodgkin Lymphoma
  • Lymphoma, Non-Hodgkin (NHL)
  • Myelodysplastic Syndrome (MDS)
  • Haploidentical stem cell transplant
  • Allogeneic stem cell transplant
  • Mismatched family member stem cell donor transplant
  • Bone marrow transplant
  • High risk hematologic malignancies
  • T cell depletion methodology
  • Miltenyi Biotec CliniMACS stem cell selection device
  • Campath-1H intravenous
  • Neoplasms
  • Hemoglobinuria
  • Hemoglobinuria, Paroxysmal
  • Hodgkin Disease
  • Leukemia
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Myelomonocytic, Chronic
  • Acute Disease
  • Leukemia, Myelomonocytic, Juvenile
  • Hematologic Neoplasms

Name

Location

St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794