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AzTrials

LeukemiaPhase 1NCT00376480

Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant

A Phase 1 study testing anti-thymocyte globulin, peripheral blood lymphocyte therapy and fludarabine phosphate in people with Leukemia and Myelodysplastic Syndromes, run by Dana-Farber Cancer Institute at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Giving total-body irradiation and chemotherapy, such as thiotepa and fludarabine, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also 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 50 years
Conditions the study is for
Leukemia, Myelodysplastic Syndromes
What is being tested?
anti-thymocyte globulin, peripheral blood lymphocyte therapy and fludarabine phosphate
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
6 sitesUnited States
Study dates
Jun 2005to 16 May 2018
Phase
Phase 1
Are there results?
None posted in the registry

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 50 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:
  • Acute lymphocytic leukemia
  • In ≥ second complete remission (CR), defined as < 5% blasts in bone marrow (BM) and no active extramedullary disease OR in first CR with any of the following high risk features:
  • History of induction failure
  • Philadelphia chromosome positive
  • t(4;11) by cytogenetic analysis
  • Any infant with MLL rearrangements on cytogenetic analysis
  • No relapse with isolated extramedullary disease after completion of prior treatment
  • Acute myeloid leukemia
  • Failed induction therapy after < 3 courses
  • In ≥ second CR, defined as < 5% blasts in BM and no active extramedullary disease OR in first CR with any of the following high-risk features:
  • History of induction failure = 5q- or monosomy 7 cytogenetic findings
  • Any of the following myelodysplastic syndromes:
  • Refractory anemia (RA) with excess blasts (RAEB) with a high International Prognostic Scoring System (IPSS) score or score of intermediate-1(INT-1) or intermediate-2 (INT-2)
  • RAEB in transformation with INT-1, INT-2, or high IPSS score
  • RA with INT-2 score
  • Patients must have a healthy, related donor who is at least genotypically HLA-A, B, C, and DR haploidentical to the patient
  • No suitably matched family donor defined by genotypic or phenotypic identity for ≥ 5/6 A, B, or DR loci
  • No immediately available genotypically matched (6/6) unrelated marrow donor
  • No immediately available umbilical cord blood donor with suitable cell dose after a search ≥ 2 months
  • Patients whose medical condition is at high risk of deteriorating or whose disease is at high risk of progression during a donor search are eligible
  • Has a parent with a haplotype that is disparate from that of the donor for the haplotype shared by the patient and parent, but not shared by the patient and donor OR patient is able to donate sufficient autologous cells by peripheral blood draw or unstimulated leukapheresis
  • No active CNS disease

PATIENT CHARACTERISTICS:

  • Room air O_2 saturation > 95% unless the lungs are involved with disease
  • No clinical evidence of pulmonary insufficiency unless the lungs are involved with disease
  • AST and ALT < 3 times upper limit of normal (ULN)*
  • Bilirubin < 2.0 mg/dL*
  • Creatinine < 2 times ULN OR creatinine clearance or glomerular filtration rate > 50% of the lower limit of normal
  • LVEF > 45% OR shortening fraction > 20%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active infection, defined as absence of an infectious diagnosis or (in patients who have had a recent positive infectious diagnosis) the resolution of fever, documentation of negative cultures or antigen testing, continuation or completion of a course of appropriate therapy, and presence of stable to resolving clinical symptoms
  • No evidence of HIV infection OR known HIV positivity NOTE: *Does not apply if liver is involved with disease

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior stem cell transplantation
  • No other concurrent immunosuppressive therapy

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Children's Hospital Boston

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of Florida Health Science Center - Gainesville

    Gainesville, Florida, 32610

  • M. D. Anderson Cancer Center at University of Texas

    Houston, Texas, 77030-4009

  • Childrens Hospital Los Angeles

    Los Angeles, California, 90027-0700

Other trials in United States

About this study

Official title: Delayed Infusion of Ex Vivo Anergized Peripheral Blood Mononuclear Cells Following CD34 Selected Peripheral Blood Stem Cell Transplantation From a Haploidentical Donor for Patients With Acute Leukemia and Myelodysplasia

RATIONALE: Giving total-body irradiation and chemotherapy, such as thiotepa and fludarabine, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy 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. Giving methylprednisolone and antithymocyte globulin before transplant and peripheral blood cells that have been treated in the laboratory after transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases.

Read the detailed description

OBJECTIVES:

Primary

  • Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells (PBMC) after CD34 (cluster designation 34)-selected megadose haploidentical hematopoietic stem cell transplantation (HSCT) in patients with hematopoietic cancers or other diseases.
  • Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the nonshared donor-recipient haplotype in these patients.
  • Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo anergization.
  • Determine the number of transplanted individuals who meet the criteria for proceeding to delayed infusion of ex vivo anergized donor PBMC.
  • Establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximum number of donor T cells that can be infused without unacceptable graft-versus-host disease.

Secondary

  • Evaluate, in vitro, the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization.
  • Assess, in vitro, the function of immune cells engrafted in these patients.
  • Assess, in vitro, whether alloantigen hyporesponsive donor T cells are present in these patients.
  • Develop, preliminarily, in vitro data on the extent of pathogen-specific immunity and its rate of recovery.
  • Describe the patterns of opportunistic infections in these patients.

OUTLINE: This is a multicenter, dose-escalation study of ex vivo anergized allogeneic peripheral blood mononuclear cells (PBMC). Patients who are treated on any dose level except dose level 1 are stratified according to age (under 17 [pediatric] vs 17 and over [adult]).

  • Myeloablative conditioning regimen: Patients undergo total-body irradiation twice daily on days -11 to -9. Patients also receive thiotepa IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 30 minutes on days -7 to -3, and anti-thymocyte globulin IV over 8 hours and methylprednisolone IV over 15-30 minutes on days -6 to -3.
  • Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo CD34-selected PBSCT on day 0.
  • Ex vivo anergized allogeneic PBMC infusion: If cells have engrafted and patients are free of active uncontrolled infection and graft-vs-host disease, patients undergo allogeneic or autologous PBMC infusion on day 35 or 42.

Cohorts of 3-8 patients receive escalating doses of ex vivo anergized allogeneic PBMCs until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 5 or 3 of 8 patients experience dose-limiting toxicity.

After completion of study, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Being tested
anti-thymocyte globulin, peripheral blood lymphocyte therapy, fludarabine phosphate, methylprednisolone, thiotepa
Keywords
refractory anemia with excess blasts in transformation, adult acute lymphoblastic leukemia in remission, refractory anemia with excess blasts, refractory anemia, adult acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), secondary myelodysplastic syndromes, childhood myelodysplastic syndromes
Medical subject headings
Leukemia, Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts, Anemia, Refractory, Congenital Abnormalities

What participants receive

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

Study groups in NCT00376480
Study groupRoleWhat they receive
administration of adoptive donor lymphocyte infusionExperimentaladministration of donor lymphocytes made using costimulatory blockade ex vivo
Receives: Biological: anti-thymocyte globulin; Biological: peripheral blood lymphocyte therapy; Drug: fludarabine phosphate; Drug: methylprednisolone; Drug: thiotepa; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: in vitro-treated peripheral blood stem cell transplantation; Radiation: total-body irradiation

What is being measured

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

  1. Feasibility of making and administering the adoptive T cell product

    ability to collect sufficient cells, make anergized product with good viability, without contamination and infuse per study toxicity of the conditioning regimen, the likelihood of engraftment, and the subsequent percentage of individuals who would be eligible to receive aDLI were determined.

    Measured: from conditioning through administration of anergized cells on day 35-42

  2. Safety of administering the adoptive T cell product on day 35-42 post haploidentical transplant

    rates of graft failure with CD34 selected product, adverse and severe adverse reactions attributable to infusion of anergized donor cells, including fever, hypotension, acute graft vs host disease, organ dysfunction

    Measured: the period from aDLI infusion through D100

  3. Alloreactivity engendered by administering the adoptive T cell product

    occurrence and severity of acute GVHD

    Measured: from cell infusion through day 100

Secondary outcomes (1)

  1. Efficacy in restoring adaptive immunity

    incidence of viral infection and type of immune reconstitution by phenotype and function of T cells

    Measured: from aDLI thorough 1 year

Timeline

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

  1. First posted15 Sep 2006 (estimated)
  2. Study startJun 2005
  3. Primary completionJun 2010
  4. Study completion16 May 2018

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00376480
Sponsor's protocol ID
05-030
Other IDs
P01CA100265, P30CA006516, MDA-2005-0695
Status last verified
Jul 2019
First submitted
13 Sep 2006
Last updated
5 Jul 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Davies JK, Brennan LL, Wingard JR, Cogle CR, Kapoor N, Shah AJ, Dey BR, Spitzer TR, de Lima M, Cooper LJ, Thall PF, Champlin RE, Nadler LM, Guinan EC. Infusion of Alloanergized Donor Lymphocytes after CD34-selected Haploidentical Myeloablative Hematopoietic Stem Cell Transplantation. Clin Cancer Res. 2018 Sep 1;24(17):4098-4109. doi: 10.1158/1078-0432.CCR-18-0449. Epub 2018 May 16.

    PubMed 29769208

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing anti-thymocyte globulin, peripheral blood lymphocyte therapy and fludarabine phosphate in people with Leukemia and Myelodysplastic Syndromes, run by Dana-Farber Cancer Institute at 6 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: finished, as of the sponsor's last update on 5 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Feasibility of making and administering the adoptive T cell product (time frame: from conditioning through administration of anergized cells on day 35-42). The study lists 3 primary outcomes in all. 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 NCT00376480, which also lists 1 linked publication.

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 5 Jul 2019.

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