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AzTrials

Graft Versus Host DiseasePhase 2NCT00450983

Donor Peripheral Stem Cell Transplant and Donor Natural Killer Cell Transplant After Total-Body Irradiation, Thiotepa, Fludarabine, and Muromonab-CD3 in Treating Patients With Leukemia or Other Blood Diseases

A Phase 2 study testing muromonab-CD3, natural killer cell therapy and fludarabine phosphate in people with Graft Versus Host Disease and Leukemia, run by Fred Hutchinson Cancer Center at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell and donor natural killer cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study

Who is it for?
Ages Up to 45 years
What is being tested?
muromonab-CD3, natural killer cell therapy and fludarabine phosphate
Type of treatment
Surgery or procedure
How many people
1 participants
Where
2 sitesUnited States
Study dates
Dec 2006to Jul 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following life-threatening hematological malignancies:
  • Acute lymphoblastic leukemia meeting 1 of the following criteria:
  • Advanced beyond first remission
  • In first remission with high-risk prognostic features, including any of the following:
  • Philadelphia chromosome-positive disease
  • Chromosome 11q23 abnormality
  • Hypodiploid
  • Failed to achieve first remission within 1 month after induction
  • Acute myeloid leukemia (AML) meeting 1 of the following criteria:
  • Advanced beyond first remission
  • First remission with high-risk prognostic features, including any of the following:
  • Chromosome 11q23 abnormality
  • Chromosome del 7q
  • Secondary AML
  • Failed to achieve first remission within 1 month after induction
  • Myelodysplastic syndromes with International Prognostic Score > 1
  • Chronic myelogenous leukemia in accelerated or blastic phase
  • No active CNS disease
  • No suitable HLA-matched related or unrelated donor available
  • Haploidentical family member available as donor of partially HLA-matched peripheral blood stem cells
  • Least degree of mismatch to HLA-A, B, C, DRB1, and DQB1
  • No mismatch for a single HLA-A, B, C, DRB1, or DQB1 antigen
  • Donor killer cell immunoglobulin-like receptor ligand group expression preferably different than patient

PATIENT CHARACTERISTICS:

  • LVEF ≥ 45%
  • DLCO ≥ 60% of predicted
  • AST and ALT ≤ 2 times upper limit of normal (ULN) (unless due to malignancy)
  • Bilirubin ≤ 2 times ULN (unless due to malignancy)
  • No life expectancy < 6 months due to coexisting disease other than the malignancy
  • No active infection (e.g., polymerase chain reaction [PCR] evidence for cytomegalovirus, human herpes virus 6, or invasive fungal infection)
  • No prior infections without evidence of resolution by PCR or imaging studies within the past 2 months
  • No hypersensitivity to murine antibodies
  • No known HIV positivity
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No prior marrow transplantation with total body irradiation > 400 cGy
  • No concurrent therapies for seizure disorder
  • No growth factors for 21 days after transplantation

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109-1023

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109-1024

Other trials in United States

About this study

Official title: Transplantation of Haploidentical CD34+ Purified Peripheral Blood Stem Cells With NK-Cell Add-Back Following Conditioning With Total Body Irradiation, Thiotepa, Fludarabine and OKT3

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell and donor natural killer cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving a donor peripheral stem cell transplant and a donor natural killer cell transplant after total-body irradiation, thiotepa, fludarabine, and muromonab-CD3 works in treating patients with leukemia or other blood diseases.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the effect of haploidentical donor CD34+ purified peripheral blood stem cells and donor natural killer (NK) cells on the risk of developing grades III-IV acute graft-vs-host disease in patients with leukemia or other hematologic diseases.

Secondary

  • Determine the risk for mortality from infection before day 180 in patients treated with this regimen.
  • Determine the risk for graft rejection in patients treated with this regimen.
  • Determine the risk for life-threatening infections in patients treated with this regimen.
  • Determine the concentration of subsets of NK, NK-T, T cells, and dendritic cells in the CD34+ NK/NK-T-enriched graft.
  • Determine cytomegalovirus-specific T-cells in product and donor graft.
  • Determine the genotype and phenotype of donor killer cell immunoglobulin-like receptor expression according to time after hematopoietic stem cell transplantation (HSCT).
  • Determine the reconstitution of NK function according to time after HSCT.
  • Determine the expression of NKG2 ligands of leukemic blasts.

OUTLINE: Patients are stratified according to age (≤ 7 years vs > 7 years).

  • Conditioning regimen: Patients 7 years of age or younger undergo total-body irradiation (TBI) twice daily on days -11 to -9. Patients over 7 years of age undergo TBI once on day -9. All patients receive thiotepa IV over 2 hours on days -8 and -7, fludarabine phosphate IV on days -6 to -3 and muromonab-CD3 on days -6 to 6. Patients with acute lymphoblastic leukemia or leukemia in the spinal fluid also receive methotrexate intrathecally prior to and after donor peripheral blood stem cell (PBSC) transplantation .
  • Donor PBSC transplantation: Patients undergo donor PBSC transplantation comprising CD34+ purified PBSCs and natural killer (NK) cells on day 0.

Blood samples are collected in weeks 1-4, 6, 8, and 12. Analysis of samples includes quantitation of NK, NK-T, and T-cell subsets (CD3, CD4, and CD8) by flow cytometry; donor killer cell immunoglobulin-like receptor genotype and phenotype; interferon-gamma levels; and NK cytotoxicity. Samples are also analyzed by leukemic blast assay to determine if ligands that activate NK cells are expressed.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Being tested
muromonab-CD3, natural killer cell therapy, fludarabine phosphate, methotrexate, thiotepa
Keywords
graft versus host disease, adult acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, childhood acute lymphoblastic leukemia in remission, recurrent childhood acute lymphoblastic leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, childhood acute myeloid leukemia in remission, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12)
Medical subject headings
Graft vs Host Disease, Leukemia, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Congenital Abnormalities, Leukemia, Myeloid, Acute, Leukemia, Myeloid, Accelerated Phase, Blast Crisis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD)

    Count of participants with acute GVHD grades III-IV.

    Measured: Up to day 100

Secondary outcomes (8)

  1. Risk for Mortality From Infection Before Day 180

    Count of participant deaths from infection up to day 180.

    Measured: Up to day 180

  2. Risk for Graft Failure

    Count of participant that had graft failure.

    Measured: Engraftment documented day +20

  3. Risk for Life-threatening Infections

    Count of participants with life-threatening infections

    Measured: Up to day 100

  4. Concentration of NK, NK-T, T-cells, and Dendritic Cell Subsets in the CD34+ NK/NK-T-enriched Graft

    Measured: Up to 5 years

  5. Cytomegalovirus-specific T Cells in Product and Donor Graft

    Measured: Up to 5 years

  6. Genotype and Phenotype of Donor Killer Cell Immunoglobulin-like Receptor Expression According to Time After Hematopoietic Stem Cell Transplantation (HSCT)

    Measured: Up to 5 years

  7. Reconstitution of NK Function According to Time After HSCT

    Measured: Up to 5 years

  8. Expression of NKG2 Ligands of Leukemic Blasts

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2007 (estimated)
  2. Study startDec 2006
  3. Primary completionJul 2010
  4. Study completionJul 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00450983
Sponsor's protocol ID
1965.00
Other IDs
R01AI053193, P30CA015704, FHCRC-1965.00, CDR0000533834
Status last verified
Apr 2017
First submitted
20 Mar 2007
Last updated
24 May 2017
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing muromonab-CD3, natural killer cell therapy and fludarabine phosphate in people with Graft Versus Host Disease and Leukemia, run by Fred Hutchinson Cancer Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD) (time frame: Up to day 100). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00450983.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2017.

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