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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT00145626
Other study ID # INFT2
Secondary ID NCI-2011-03671
Status Active, not recruiting
Phase Phase 2
First received September 1, 2005
Last updated January 20, 2016
Start date May 2004
Est. completion date June 2016

Study information

Verified date January 2016
Source St. Jude Children's Research Hospital
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

Recent studies of conventional chemotherapy for infants with high-risk hematologic malignancies show that the long-term disease-free survival is low. Although blood and marrow stem cell transplantation using an HLA identical sibling has improved the outcome for these children, less than 25% have this donor source available. Another option is haploidentical transplantation using a partially matched family member donor (i.e. parental donor).

Although haploidentical transplantation has proven curative for some patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including infection and graft versus host disease (GVHD). Building on prior institutional trials, this study will provide patients a haploidentical graft depleted of T lymphocytes using the investigational device, CliniMACS selection system. One week after the transplant procedure, patients will also receive an infusion of additional donor derived white blood cells called Natural Killer (NK) cells in an effort to decrease risks for rejection of the graft, disease relapse, and regimen related toxicity. The primary objective of the study is to evaluate 1 year survival in infants with high risk hematologic malignancies who receive this study treatment.


Description:

Secondary objectives for this study include the following:

- To estimate the incidence of three transplant-related adverse outcomes (i.e., regimen-related mortality, engraftment failure, and fatal acute GVHD) in the first 100 days after transplantation.

- To estimate the incidence of chronic graft-versus-host disease.

- To evaluate those factors that affect one-year survival.

- To assess the kinetics of lymphohematopoietic reconstitution.

- To assess the frequency and clinical relevance of minimal residual disease (MRD) before and after transplantation.

- To evaluate the incidence of and risk factors for long-term neurocognitive deficit and organ dysfunction.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 40
Est. completion date June 2016
Est. primary completion date March 2015
Accepts healthy volunteers No
Gender Both
Age group N/A to 24 Months
Eligibility Inclusion Criteria:

Must have one of the following diagnosis:

- AML in remission or relapse (e.g., FAB M7 or biphenotypic leukemia)

- High-risk ALL in first remission (e.g., poor responder to prednisone, Ph+ ALL)

- ALL beyond first remission

- Secondary leukemia

- Primary myelodysplasia (including RAEB, RAEB-T, CMML, JCML, and JMML)

- Chronic myeloid leukemia

- Histiocytoses (including multi-system Langerhans' cell histiocytosis and hemophagocytic lymphohistiocytosis

Inclusion criteria Donor research participants

- HIV negative (date).

- Hepatitis B surface antigen negative (date).

- Hepatitis C antibody negative (date).

- Syphilis negative (date).

- Donor is equal to or greater than 3 on 6 HLA match (date).

- Not pregnant (negative pregnancy test).

- Not lactating.

- At least 18 years of age.

Exclusion Criteria

- Patients greater than 24 months of age at the time of transplant.

- HLA-identical sibling donor is available.

- Cardiac function: shortening fraction <25%.

- Pulse oximetry oxygen saturation <92% on room air.

- Glomerular filtration rate less than 40 ml/min/1.73 m2 (may use Technetium-99 result for GFR).

- Direct bilirubin > 3 mg/dl.

- SGPT > 500 U/L.

- Patients with previous allergy to mouse proteins.

- Patients with previous allergy to rabbit serum products.

- Patients with Down's syndrome

Study Design

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


Related Conditions & MeSH terms


Intervention

Drug:
Chemotherapy and antibodies
Study participants will receive a non-TBI based preparative regimen consisting of Cyclophosphamide, fludarabine, thiotepa, melphalan, and muromonab-CD3 (OKT3) followed by an infusion of a T-lymphocyte depleted haploidentical hematopoietic stem cell graft. Seven days posttransplant, participants will receive an infusion of additional donor derived cells called NK cells.
Device:
Miltenyi Biotec CliniMACS
Stem cell selection device
Procedure:
Allogeneic stem cell transplantation
Allogeneic natural killer (NK)cell infusion

Locations

Country Name City State
United States St. Jude Children's Research Hospital Memphis Tennessee

Sponsors (2)

Lead Sponsor Collaborator
St. Jude Children's Research Hospital Assisi Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary One-year Survival The one-year survival of infants with high-risk hematologic malignancies who receive a haploidentical transplant procedure using a total body irradiation (TBI)-excluding conditioning regimen followed by an HLA-nonidentical family donor hematopoietic stem cell (HSC) graft depleted of T cells ex vivo using the CliniMACS CD34+ selection system, with a subsequent infusion of donor NK cells purified ex vivo using the CliniMACS CD3+ depletion and CD56+ enrichment system.
The Kaplan-Meier estimate for one-year survival is reported.
One year after transplant Yes
Secondary Number of Transplant-Related Adverse Outcomes: Regimen-Related Mortality The cumulative incidences of regimen-related mortality will be estimated using method of Kalbfleisch and Prentice. 100 days post-transplantation Yes
Secondary Number of Transplant-Related Adverse Outcomes: Engraftment Failure Engraftment failure is defined as <10% donor cell chimerism at any time point between 28 and 100 days after transplant with no evidence of disease relapse or requiring stem cell boost. 100 days post-transplantation Yes
Secondary Number of Transplant-Related Adverse Outcomes: Fatal Acute Graft-Versus Host Disease (GVHD) The cumulative incidence estimate for occurrence of fatal acute GVHD by the end of the first 100 days post-transplant was calculated using method of Kalbfleisch and Prentice. 100 days post-transplantation Yes
Secondary Number of Transplant-related Adverse Outcomes Adverse outcomes include regimen-related mortality, engraftment failure, and fatal acute graft-versus-host-disease (GVHD).
The cumulative incidences of regimen-related mortality will be estimated using method of Kalbfleisch and Prentice. The estimate of the incidence of engraftment failure and fatal acute GVHD will be obtained using Binomial distribution. Engraftment failure is defined as <10% donor cell chimerism at any time-point between 28-100 days after transplant with no evidence of disease relapse, or anyone requiring stem cell boost.
5 Years No
Secondary Number of Incidences of Chronic GVHD. The estimate of the incidence of chronic GVHD will be obtained using Binomial distribution. Up to 5 years after transplant Yes
Secondary Factors Affecting One-year Survival: Median Age of Donor at HSCT Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model). Up to one year after transplant No
Secondary Factors Affecting One-year Survival: Median Dose of CD34 Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model). Up to one year after transplant No
Secondary Factors Affecting One-year Survival: Median Dose of NK Cells Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model). Up to one year after transplant No
Secondary Factors Affecting One-year Survival: Disease Status at HSCT Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model). Up to one year after transplant No
Secondary Factors Affecting One-year Survival: Donor Type Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model). Up to one year after transplant No
Secondary Factors Affecting One-year Survival: Match N/6 HLA Loci HLA typing determined the degree of match by looking at 6 different HLA loci. The results indicate the number of the 6 loci that matched for each participant. Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model). Up to one year after transplant No
Secondary Factors Affecting One-year Survival: Minimal Residual Disease (MRD) Detection of leukemia blasts in bone marrow by flow cytometry Up to one year after transplant No
Secondary The Kinetics of Lymphohematopoietic Reconstitution. The lymphohematopoietic reconstitution will be assessed in a longitudinal manner and analyzed accordingly. Up to 5 years after transplant No
Secondary The Incidence of and Risk Factors for Organ Dysfunction. The organ dysfunction will be summarized using summary statistics and assessed in a longitudinal manner and analyzed accordingly. Up to 5 Years after transplant No
Secondary The Incidence of and Risk Factors for Long-term Neurocognitive Deficit. The long-term neurocognitive deficit will be summarized using summary statistics and assessed in a longitudinal manner and analyzed accordingly. Up to 5 Years after transplant No
Secondary The Frequency of and Clinical Relevance of Minimal Residual Disease (MRD) Before and After Transplantation The presence or absence of MRD before and after the bone marrow transplant (BMT) and its frequency distribution will be obtained for each time point separately. Their effect on overall survival will be evaluated using logistic regression and Cox's proportional hazard model if there is censoring. Baseline and up to 5 years after transplant No
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