Pilot Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Matched Unrelated Double Cord Blood Transplant for the Treatment of Leukemias, Lymphomas, and Pre-Malignant Blood Disorders

December 14, 2019 updated by: National Cancer Institute (NCI)

Background:

  • Allogeneic stem cell transplantation (SCT) has been used to treat many kinds of cancer or pre-cancerous conditions that develop in blood or immune system cells. Umbilical cord blood transplantation (UCBT) is a type of allogeneic transplant that is used when none of a patient s siblings are a match and an acceptable match cannot be identified from one of the bone marrow registries. Prior to receiving the cord blood stem cells, large doses of chemotherapy drugs and/or radiation have been traditionally used to eliminate most of the cancerous or abnormal cells from the recipient s system, along with most of his or her own stem cells and immune cells. Donor stem cells then replace the recipient s stem cells in the bone marrow, restoring normal blood production and immunity. In this way, an allogeneic SCT provides not only new blood cells but an entire new immune system.
  • In the past, allogeneic SCT was performed with very high doses of chemotherapy and/or radiation to get rid of as much of the recipient s cancer as possible and prevent rejection of the treatment. However, intensive chemotherapy or radiation can cause serious side effects, including death. A newer method uses smaller, less toxic doses of chemotherapy and/or radiation before allogeneic SCT. In these reduced-intensity stem cell transplants, the recipient s stem cells and immunity are not completely eliminated, but they are weakened enough to help prevent the donor s cells from being rejected.

Objectives:

- To study the safety and effectiveness of reduced-intensity stem cell transplants given with immune-depleting chemotherapy and umbilical cord blood provided by an unrelated donor.

Eligibility:

  • Individuals between 18 and 69 years of age who have been diagnosed with any of a number of cancerous and pre-cancerous blood conditions, including lymphoma and leukemia.
  • Participants must not have a potential donor sibling or a readily available unrelated donor identified through one of the bone marrow donor registries.

Design:

  • Patients will be matched with at least two umbilical cords with an acceptable cell dose. The two frozen umbilical cord blood units will be sent to the NIH prior to the date of transplant.
  • Patients will receive one, two, or three cycles of chemotherapy (based on the type of disease) to treat the disease and to weaken the immune system. Patients who already have a weakened immune system from other treatments will not receive this round of chemotherapy.
  • Patients will then receive 4 days of reduced-intensity transplant chemotherapy (also called the conditioning regimen ) to prepare for the transplant.
  • Two days after transplant chemotherapy, patients will receive the transplant, with the two umbilical cords infused one after the other on the same day. Patients will receive additional treatment to prevent complications.
  • Patients will remain in the hospital for 4 to 6 weeks after the transplant, and will be discharged for outpatient treatment when the study doctors deem it appropriate.
  • Patients will continue on medications at home to lower the risk of complications and infections, and will visit the NIH clinic regularly for the first 6 months after the transplant, and then less often for at least 5 years afterward.

Study Overview

Status

Status

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Terminated

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Detailed Description

Background:

The major limitations of umbilical cord blood transplantation (UCBT) in adults are graft rejection and delayed engraftment leading to increased infection-related morbidity and treatment related mortality (TRM). To increase engraftment rates while at the same time enhancing graft-versus-tumor effect, previous studies within our institution have employed the strategy of targeted immune depletion (TID). The goal of TID is to use T-cell suppressive chemotherapy prior to the conditioning regimen to treat the patient s disease while concurrently depleting host T-cells. This has lead to earlier complete donor chimerism in the setting of allogeneic sibling donor and matched unrelated donor transplantation. Our aim in the current protocol is to extend the strategy of TID to reduced-intensity UCBT, with the goal of more rapid engraftment, leading to decreased TRM and increased overall survival. Our intention is to investigate this approach in the setting of double cord blood transplant in adults in a pilot manner.

Objectives:

  • The primary objective of this study is to see whether targeted immune depletion can shorten the time to neutrophil recovery and improve the cord blood engraftment rate as measured by ANC greater than or equal to 500 x 3 and at least partial donor chimerism (10-90%).
  • Secondary objectives include further assessment of hematopoetic recovery, treatment related morbidity including infections and acute and chronic GVHD, TRM, progression free and overall survival, further assessment of immune reconstitution, and study of engraftment kinetics as they apply to prediction of which of the two transplanted cords will engraft in relation to cell dose, CD34+ dose, HLA-match, and other experimental variables.

Eligibility:

  • Adults (18-69 years) with advanced or high-risk hematologic malignancies including AML, ALL, MDS, CLL, NHL, HL, CML, multiple myeloma, and MPD who lack a readily available HLA-matched sibling or greater than or equal to 7/8 HLA-matched unrelated donor. Patients must have life expectancy of at least 3 months, ECOG less than or equal to 2, and relatively normal major organ functions.
  • Patients must have two partially HLA-matched UCB units. Units must be HLA-matched at HLA-A and B (intermediate resolution molecular typing) and DRB1 (high resolution molecular typing) 4-6/6 with the recipient and 4-6/6 with each other. Each unit must contain a minimum precryopreserved, nucleated cell dose of 1.5 x 10(7) per kilogram.

Design:

  • This is a Pilot study of TID in the setting of reduced-intensity double cord blood transplant in adults.
  • Patients will receive disease-specific induction chemotherapy (EPOCH-F/R or FLAG) prior to transplant for disease control and immune depletion.
  • All patients will receive an identical conditioning regimen consisting of cyclophosphamide 1200 mg/m(2)/day IV for 4 days and fludarabine 30 mg/m(2)/day for 4 days.
  • A maximum of 13 patients will be transplanted in the initial part of this pilot study. If no stopping rules are reached, the study will be expanded to allow the transplantation of an additional 12 patients (a total of 25 patients).

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 1

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
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

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

18 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • ELIGIBILITY CRITERIA:
  • Adults (18-69 years) with advanced or high-risk hematologic malignancies including AML, ALL, MDS, CLL, NHL, HL, CML, multiple myeloma, and MPD who lack a readily available HLA-matched sibling or greater than or equal to 7/8 HLA-matched unrelated donor. Patients must have life expectancy of at least 3 months, ECOG less than or equal to 2, and relatively normal major organ functions.
  • Patients must have two partially HLA-matched UCB units. Units must be HLA-matched at HLA-A and B (intermediate resolution molecular typing) and DRB1 (high resolution molecular typing) 4-6/6 with the recipient and 4-6/6 with each other. Each unit must contain a minimum precryopreserved, nucleated cell dose of 1.5 x 10(7) per kilogram.

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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
The primary objective of this study is to see whether targeted immune depletion can shorten the time to hematopoietic recovery and improve cord blood engraftment rate as measured by ANC greater than 500 X 3 and at least partial donor chimerism (...

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
Secondary objectives include further assessment of immune reconstitution, study of engraftment kinetics in relation to cell dose and HLA-match, and comprehensive assessment of acute and chronic GVHD.

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.
National Cancer Institute (NCI)

Publications and helpful links

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General Publications

Study record dates

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Study Major Dates

Study Start

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.
August 25, 2009

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 20, 2013

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 20, 2013

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).
September 5, 2009

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.
September 5, 2009

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.
September 9, 2009

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.
December 17, 2019

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.
December 14, 2019

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.
May 20, 2013

More Information

Terms related to this study

Keywords

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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.
  • 090210
  • 09-C-0210

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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