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Acute Myeloid Leukemia (AML)Phase 2NCT02433483

Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients

A Phase 2 study testing Cytarabine, Intrathecal Triples and HPC-A in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by St. Jude Children's Research Hospital at 1 site 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

Allogeneic transplant can sometimes be an effective treatment for leukemia. In a traditional allogeneic transplant, patients receive very high doses of chemotherapy and/or radiation therapy, followed by an infusion of their donor's bone marrow or blood stem cells. Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
Cytarabine, Intrathecal Triples and HPC-A
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
22 May 2015to 8 May 2017
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 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Participants must have a diagnosis of AML or myelodysplastic syndrome (MDS), ALL, and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after HSCT.
  • Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy.
  • Patients with AML must have ≥ 5% leukemic blasts in the bone marrow or have converted from negative minimal residual disease (MRD) status to positive MRD status in the bone marrow as assessed by flow cytometry. If an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood.
  • Participant is ≤ 21 years of age (i.e., has not reached 22nd birthday).
  • Adequate organ function defined as the following:
  • Total bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is > ULN, direct bilirubin is ≤ 1.5 mg/dL
Show all 25Show fewer
  • AST (SGOT)/ALT (SGPT) < 5 x ULN
  • Calculated creatinine clearance > 50 ml/min/1.73m^2 as calculated by the Schwartz formula for estimated glomerular filtration rate >
  • Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25%.
  • Has an available HPC-A donor.
  • Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are > 16 years old.
  • Does not have an uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable.
  • Patient has fully recovered from the acute effects of all prior therapy and must meet the following criteria.
  • At least 14 days must have elapsed since the completion of myelosuppressive therapy.
  • At least 24 hours must have elapsed since the completion of hydroxyurea, low-dose cytarabine (up to 200 mg/m^2/day), and intrathecal chemotherapy.
  • At least 30 days must have elapsed since the use of investigational agents.
  • For patients who have received prior HSCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HSCT. Patients cannot be receiving therapy, including steroids, for GVHD.
  • Post-menarchal female has had negative serum pregnancy test within 7 days prior to enrollment.
  • Male or female of reproductive potential has agreed to use effective contraception for the duration of study participation.
  • Not breastfeeding
  • At least 18 years of age.
  • Family member (first degree relatives).
  • Not pregnant as confirmed by negative serum or urine pregnancy test within 7 days prior to enrollment (if female).
  • Not breast feeding.
  • Meets donation eligibility requirements as outlined by 21 CFR 1271.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

Other trials in United States

About this study

Official title: A Phase II Study of Microtransplantation in Patients With Refractory or Relapsed Hematologic Malignancies

Allogeneic transplant can sometimes be an effective treatment for leukemia. In a traditional allogeneic transplant, patients receive very high doses of chemotherapy and/or radiation therapy, followed by an infusion of their donor's bone marrow or blood stem cells. The high-dose chemotherapy drugs and radiation are given to remove the leukemia cells in the body. The infusion of the donor's bone marrow or blood stem cells is given to replace the diseased bone marrow destroyed by the chemotherapy and/or radiation therapy. However, there are risks associated with allogeneic transplant. Many people have life-threatening or even fatal complications, like severe infections and a condition called graft-versus-host disease, which is caused when cells from the donor attack the normal tissue of the transplant patient.

Recently, several hospitals around the world have been using a different type of allogeneic transplant called a microtransplant. In this type of transplant, the donor is usually a family member who is not an exact match. In a microtransplant, leukemia patients get lower doses of chemotherapy than are used in traditional allogeneic transplants. The chemotherapy is followed by an infusion of their donor's peripheral blood stem cells. The objective of the microtransplant is to suppress the bone marrow by giving just enough chemotherapy to allow the donor cells to temporarily engraft (implant), but only at very low levels. The hope is that the donor cells will cause the body to mount an immunologic attack against the leukemia, generating a response called the "graft-versus-leukemia" effect or "graft-versus-cancer" effect, without causing the potentially serious complication of graft-versus-host disease.

With this research study, the investigators hope to find out whether or not microtransplantation will be a safe and effective treatment for children, adolescents and young adults with relapsed or refractory hematologic malignancies

Read the detailed description

PRIMARY OBJECTIVES:

  • To assess the safety and feasibility of standard chemotherapy plus GCSF-mobilized Hematopoietic Progenitor Cell, Apheresis (HPC-A) in pediatric patients with relapsed or refractory hematologic malignancies.
  • To estimate the response rates to standard chemotherapy plus GCSF-mobilized HPC-A in pediatric patients with relapsed or refractory hematologic malignancies.

SECONDARY OBJECTIVES:

  • To describe the event-free and overall survival of patients treated with standard chemotherapy plus GCSF-mobilized HPC-A.
  • To estimate the time to neutrophil and platelet recovery after treatment with standard chemotherapy plus GCSF-mobilized HPC-A.
  • To determine the cumulative incidence of acute and chronic graft-versus-host disease (GVHD).

OTHER PRESPECIFIED OBJECTIVES:

  • To characterize donor chimerism and microchimerism.

Patients will receive standard chemotherapy followed by infusion of donor peripheral blood mononuclear cells 2 days after the completion of chemotherapy. Patients who have at least a partial response are eligible to receive a second cycle.

Diagnostic lumbar puncture and intrathecal (IT) chemotherapy will be given prior to cycle 1. Patients without evidence of central nervous system (CNS) leukemia will receive no further IT therapy during cycle 1. Patients with CNS disease will receive weekly IT therapy (age-adjusted methotrexate, hydrocortisone, and cytarabine) until the cerebrospinal fluid (CSF) becomes free of leukemia (minimum of 4 doses).

Bone marrow aspiration (BMA) and biopsy to assess response will be performed on approximately day 29 of therapy.

For hematopoietic stem cell mobilization, donors will receive G-CSF (Filgrastim) (Neupogen®) each day for 5 days given subcutaneously (SQ) prior to HPC-A collected by leukapheresis on day 6.

Being tested
Cytarabine, Intrathecal Triples, HPC-A
Keywords
Adolescent, Children, Microtransplant, Leukemia
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia

What participants receive

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

  • CytarabineDrug

    Also called Cytosine arabinoside, Ara-C, Cytosar®

    Given by either intrathecal (IT) or intravenous (IV) route.

  • Intrathecal TriplesDrug

    Also called ITMHA, Methotrexate/hydrocortisone/cytarabine

    given IT.

  • HPC-ABiological

    Also called Donor infusion, Hematopoietic Progenitor Cell, Apheresis

    Given IV.

Study groups in NCT02433483
Study groupRoleWhat they receive
Myeloid MalignanciesExperimentalIncludes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A. Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses). Interventions: * Cycle 1: cytarabine, HPC-A donor infusion * Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion
Receives: Drug: Cytarabine; Drug: Intrathecal Triples; Biological: HPC-A

What is being measured

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

  1. Number of Participants by Stratum Who Complete 2 Cycles of Therapy

    If two or more patients die from causes other than leukemia progression or experience ≥ Grade 3 GVHD that is associated with detectable donor chimerism due to this protocol, or demonstrate persistent engraftment defined as >5% donor chimerism at the time of count recovery (ANC > 0.3 x 10^9/L and platelet count > 30 x 10^/L), then the cohort will close due to intolerability. Any subject who transfers to transplant prior to completion of two courses without experiencing an unacceptable toxicity is considered inevaluable for purposes of evaluating tolerability. Accrual will be halted for intolerability if there are two or more failures in tolerability among the first six subjects who are evaluable for tolerability.

    Measured: At the end of therapy cycle 2 (approximately 2-3 months)

  2. Proportion of Participants Who Experience Therapeutic Success

    All patients will be counted towards this two-stage design. Therapeutic success for patients at time of enrollment is defined as:

    • Patients with fewer than 5% blasts, a ≥ 10-fold decrease in level of minimal residual disease after completion of 1 or 2 cycles of therapy.
    • Patients with greater than 5% in leukemic blasts in the marrow, achieving CR or CRi after completion of 1 or 2 cycles of therapy.

    In terms of efficacy, patients who die before achieving therapeutic success will be counted as a failure, and all patients who receive ≥ 1 dose of protocol chemotherapy will be counted as a failure or success. Only subjects who withdraw or die prior to receiving the first dose of protocol chemotherapy will be considered inevaluable and replaced. The evaluation of tolerability and this phase II design will be performed concurrently, i.e., the first enrollees will be counted for both tolerability and efficacy.

    Measured: At the end of therapy cycle 2 (approximately 2-3 months)

Secondary outcomes (6)
  1. 3-year Event Free Survival (EFS)

    We will use the Kaplan-Meier method to describe event-free survival. EFS will be defined as the time from enrollment to death, relapse, or refractory disease with event-free subjects' time censored at the date of last follow-up.

    Measured: 3 years after enrollment of the last participant

  2. 3-year Overall Survival (OS)

    We will use the Kaplan-Meier method to describe overall survival. Overall survival will be defined as the time from enrollment to death, with living subjects' time censored at the date of last follow-up

    Measured: 3 years after enrollment of the last participant

  3. Median Time to Neutrophil Recovery

    The time to neutrophil recovery will be summarized using descriptive statistics. If there are no deaths prior to recovery of neutrophils, nonparametric confidence intervals for the median time to recovery will be computed by inverting the sign test. Otherwise, we will compute cumulative incidence curves to describe the time to platelet and neutrophil recovery while adjusting for competing events.

    Measured: From start of therapy to completion of therapy (approximately 1 year)

  4. Time to Platelet Recovery

    The time to platelet recovery will be summarized using descriptive statistics. If there are no deaths prior to recovery of platelets, nonparametric confidence intervals for the median time to recovery will be computed by inverting the sign test. Otherwise, we will compute cumulative incidence curves to describe the time to platelet and neutrophil recovery while adjusting for competing events.

    Due to the small number of patients enrolled, the data is presented by patient.

    Measured: From start of therapy to completion of therapy (approximately 1 year)

  5. 1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD)

    Children's Oncology Group (COG) Stem Cell Committee Consensus Guidelines for Establishing Organ Stage and Overall Grade of Acute Graft Versus Host Disease (GVHD) were used. Overall clinical grade was based on the highest stage obtained:

    • Grade 0: no stage 1-4 of any organ
    • Grade I: stage 1-2 skin and no liver or gut involvement
    • Grade II: stage 3 skin, or stage 1 liver involvement, or stage 1 GI
    • Grade III: stage 0-3 skin, with stage 2-3 liver, or stage 2-3 GI
    • Grade IV: stage 4 skin, liver or GI involvement

    Measured: From start of therapy through completion of therapy (approximately 1 year)

  6. 1-year Cumulative Incidence of Chronic Graft Versus Host Disease (GVHD)

    All grades of GVHD will be reported.

    Measured: From start of therapy through completion of therapy (approximately 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 posted5 May 2015 (estimated)
  2. Study start22 May 2015
  3. Primary completion8 May 2017
  4. Study completion8 May 2017

Why it stopped: The study was closed due to poor accrual and because of competing protocols.

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
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02433483
Sponsor's protocol ID
MITREL
Other IDs
NCI-2015-00691
Status last verified
Sep 2017
First submitted
29 Apr 2015
Last updated
1 Nov 2017
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cytarabine, Intrathecal Triples and HPC-A in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by St. Jude Children's Research Hospital at 1 site 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?

The sponsor lists 25 inclusion and 0 exclusion criteria. 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 1 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 1 Nov 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?

Number of Participants by Stratum Who Complete 2 Cycles of Therapy (time frame: At the end of therapy cycle 2 (approximately 2-3 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 1 Nov 2017.

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