Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients

October 4, 2017 updated by: St. Jude Children's Research Hospital

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA - AML and MDS PARTICIPANTS

  • 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
    • 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

INCLUSION CRITERIA - HPC-A CELL DONOR

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Myeloid Malignancies

Includes 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
Drug: Cytarabine
Given by either intrathecal (IT) or intravenous (IV) route.
Other Names:
  • Ara-C
  • Cytosine arabinoside
  • Cytosar®
Drug: Intrathecal Triples
given IT.
Other Names:
  • ITMHA
  • Methotrexate/hydrocortisone/cytarabine
Biological: HPC-A
Given IV.
Other Names:
  • Donor infusion
  • Hematopoietic Progenitor Cell, Apheresis

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants by Stratum Who Complete 2 Cycles of Therapy
Time Frame: At the end of therapy cycle 2 (approximately 2-3 months)
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.
At the end of therapy cycle 2 (approximately 2-3 months)
Proportion of Participants Who Experience Therapeutic Success
Time Frame: At the end of therapy cycle 2 (approximately 2-3 months)

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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
3-year Event Free Survival (EFS)
Time Frame: 3 years after enrollment of the last participant
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.
3 years after enrollment of the last participant
3-year Overall Survival (OS)
Time Frame: 3 years after enrollment of the last participant
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
3 years after enrollment of the last participant
Median Time to Neutrophil Recovery
Time Frame: From start of therapy to completion of therapy (approximately 1 year)
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.
From start of therapy to completion of therapy (approximately 1 year)
Time to Platelet Recovery
Time Frame: From start of therapy to completion of therapy (approximately 1 year)

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.
From start of therapy to completion of therapy (approximately 1 year)
1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD)
Time Frame: From start of therapy through completion of therapy (approximately 1 year)

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
From start of therapy through completion of therapy (approximately 1 year)
1-year Cumulative Incidence of Chronic Graft Versus Host Disease (GVHD)
Time Frame: From start of therapy through completion of therapy (approximately 1 year)
All grades of GVHD will be reported.
From start of therapy through completion of therapy (approximately 1 year)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent Donor Chimerism
Time Frame: At weeks 1, 2, 3, and 4 after infusion of HPC-A
Percent donor chimerism in blood and bone marrow.
At weeks 1, 2, 3, and 4 after infusion of HPC-A

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
St. Jude Children's Research Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Cookies for Kids' Cancer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 22, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 8, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 8, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 29, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 5, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 1, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MITREL
  • NCI-2015-00691 (Registry Identifier: NCI Clinical Trial Registration Program)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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