AlloHCT From Matched Unrelated Donors in Pts w/ Advanced Hematologic Malignancies & Disorders

June 4, 2024 updated by: City of Hope Medical Center

Allogeneic Stem Cell Transplantation for Patients With Hematological Malignancies Using Multiple Unrelated Cord Blood Units

RATIONALE: Giving chemotherapy with or without total-body irradiation before a donor umbilical cord blood 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 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 cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well four different chemotherapy regimens given with or without total-body irradiation before umbilical cord blood transplant work in treating patients with relapsed or refractory hematologic cancer.

Study Overview

Status

Status

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

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

OBJECTIVES:

Primary

  • To determine the survival at day 100 of patients with relapsed, refractory, or poor-risk hematological malignancies treated with four different preparative regimens followed by allogeneic hematopoietic stem cell transplantation (HSCT) using two unrelated umbilical cord blood (UCB) units.

Secondary

  • To determine the incidence and timing of neutrophil engraftment in patients treated with these regimens.
  • To determine the incidence and timing of platelet engraftment in patients treated with these regimens.
  • To determine the incidence and severity of acute and chronic graft-versus-host-disease (GVHD) in patients treated with these regimens.
  • To determine the survival at day 180 in patients treated with these regimens.
  • To determine the disease-free survival in patients treated with these regimens.
  • To determine the incidence of primary and secondary engraftment failure in patients treated with these regimens.
  • To determine the incidence of transplantation-related complications (e.g., infection, veno-occlusive disease of the liver, or organ toxicity) in these patients.
  • To determine the incidence of post-transplantation-related lymphoproliferative disease, secondary myelodysplastic syndromes, or other secondary malignancies in these patients.
  • To determine the incidence of relapse in patients treated with these regimens.
  • To determine post-transplantation chimerism in patients treated with these regimens.
  • To determine immune reconstitution in patients treated with these regimens.

OUTLINE: This is a multicenter study.

  • Preparative regimens: Patients are assigned to 1 of 4 preparative regimens.

    • Regimen 1 (for patients < 50 years of age and no contraindication to fractionated total-body irradiation (FTBI): Patients undergo FTBI 2-3 times a day on days -9 to -6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2.
    • Regimen 2 (for patients < 50 years of age and unable to tolerate FTBI due to prior dose-limiting radiotherapy or significant cardiotoxicity): Patients receive a test dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on days -5 to -2.
    • Regimen 3* (for patients unable to tolerate regimen 1 or 2; no age exclusion): Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV over 2 hours on day -3 and undergo TBI (single dose) on day -2.
    • Regimen 4* (for patients unable to tolerate regimen 1 or 2): Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2.

NOTE: *Treating physician decides the choice between regimen 3 and 4

  • Umbilical cord blood (UCB) transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover.
  • Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

After completion of study therapy, patients are followed periodically.

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.
10

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.
  • Not Applicable

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
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Banner Good Samaritan Medical Center
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope Medical Center

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

1 second to 120 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed hematological or lymphatic malignancy, including any of the following:

    • Acute myeloid leukemia

      • Relapsed or primary refractory disease with < 10% blasts on peripheral blood smear
      • In first remission with poor risk factors and molecular prognosis [i.e., AML with -5, -7, t(6;9), tri8, -11] (preparative regimen 3 or 4)

    • Acute lymphocytic leukemia

      • In second complete remission or higher OR in first remission with poor risk factors, including any of the following (preparative regimen 1 or 2):

        • BCR/ABL by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction
        • t(9;22)(q34;q11) detected by cytogenetics
        • Chromosomes < 44 by cytogenetics
        • DNA index < 0.81 by flow cytometry
        • Any rearrangement of chromosome 11 that results in disruption of MLL gene (11q23) by cytogenetics and SER
      • In first remission with poor risk factors and molecular prognosis [ALL with Philadelphia chromosome-positive t(9;22), t(4;22), (q34;q11)] (preparative regimen 3 or 4)

    • Chronic myelogenous leukemia

      • In accelerated phase or greater (preparative regimen 1 or 2)
      • In accelerated or second chronic phase (preparative regimen 3 or 4)

    • Myelodysplastic syndromes

      • With deletion of chromosome 7 or short arm of chromosome 5 (preparative regimen 1 or 2)
      • In high and high-intermediate risk categories (preparative regimen 3 or 4)
    • Non-Hodgkin lymphoma in relapse with marrow involvement
    • Refractory chronic lymphocytic leukemia

  • Patients deemed ineligible for conventional high-dose chemotherapy programs (i.e., regimens 1 or 2) due to any of the following concurrent medical conditions may be eligible for regimens 3 or 4 at the discretion of the treating physician and principal investigator (preparative regimen 3 or 4):

    • LVEF < 50% and > 40%
    • FEV1, FVC, or DLCO < 50%
    • Bilirubin > 3 mg/dL
    • Creatinine > 2 mg/dL

  • Two partially HLA-matched umbilical cord blood (UCB) units available

    • HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and -DRB1 loci with the patient

      • DRB1 matched by high resolution DNA typing
      • HLA-A and HLA-B matched by low resolution at the "serological match" level
    • Two pooled units with a nucleated cell number > 2.5 x 10^7/kg
  • No available HLA-identical sibling or 1 antigen-mismatched related donor
  • No available HLA-matched unrelated bone marrow donor

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • Karnofsky performance status (PS) 60-100% OR Lansky PS 60-100% OR Zubrod PS 0-1
  • Physiological age 60 or less (at any chronological age)
  • Weight > 50 kg
  • Creatinine normal for age OR creatinine clearance by 24-hour urine collection or glomerular filtration rate > 60 mL/min
  • Bilirubin ≤ 1.5 mg/dL
  • LVEF ≥ 50%
  • DLCO ≥ 60% of predicted
  • No HIV-1 infection
  • No active uncontrolled infection
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • Recovered from prior intensive chemotherapy

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: Parallel 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: Regimen I (FTBI, Cyclophosphamide, Fludarabine)
Patients undergo FTBI 2-3 times a day on days -9 to -6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Drug: Cyclophosphamide
Other Names:
  • CTX
Procedure: allogeneic hematopoietic stem cell transplantation
Other Names:
  • AlloHCT
Biological: filgrastim
Drug: Cyclosporine
Other Names:
  • CsA
Procedure: umbilical cord blood transplantation
Drug: Mycophenolate Mofetil
Other Names:
  • MMF
Radiation: Fractionated total body irradiation
Other Names:
  • FTBI
Drug: Fludarabine phosphate
Other Names:
  • Fludara
Experimental: Regimen II (Busulfan, Fludarabine, Melphalan)
Patients receive a test dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Procedure: allogeneic hematopoietic stem cell transplantation
Other Names:
  • AlloHCT
Biological: filgrastim
Drug: Cyclosporine
Other Names:
  • CsA
Procedure: umbilical cord blood transplantation
Drug: Melphalan
Other Names:
  • Alkeran
Drug: Busulfan
Other Names:
  • Busilvex
Drug: Mycophenolate Mofetil
Other Names:
  • MMF
Drug: Fludarabine phosphate
Other Names:
  • Fludara
Experimental: Regimen III (TBI, Cyclophosphamide, Fludarabine)
Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV over 2 hours on day -3 and undergo TBI (single dose) on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Drug: Cyclophosphamide
Other Names:
  • CTX
Procedure: allogeneic hematopoietic stem cell transplantation
Other Names:
  • AlloHCT
Radiation: total-body irradiation
Other Names:
  • TBI
Biological: filgrastim
Drug: Cyclosporine
Other Names:
  • CsA
Procedure: umbilical cord blood transplantation
Drug: Mycophenolate Mofetil
Other Names:
  • MMF
Drug: Fludarabine phosphate
Other Names:
  • Fludara
Experimental: Regimen IV (Fludarabine, Melphalan)
Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Procedure: allogeneic hematopoietic stem cell transplantation
Other Names:
  • AlloHCT
Biological: filgrastim
Drug: Cyclosporine
Other Names:
  • CsA
Procedure: umbilical cord blood transplantation
Drug: Melphalan
Other Names:
  • Alkeran
Drug: Mycophenolate Mofetil
Other Names:
  • MMF
Drug: Fludarabine phosphate
Other Names:
  • Fludara

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
Survival Rate at Day 100 After Allogeneic Transplant From Umbilical Cord Blood (UCB)
Time Frame: From transplant to Day 100 post-transplant
Number of surviving patients at Day 100 post-transplant divided by number of patients undergone transplantation.
From transplant to Day 100 post-transplant

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
Survival Rate at Day 180 After Allogeneic Transplant From Umbilical Cord Blood (UCB)
Time Frame: From transplant up to Day 180 post-transplant
Number of surviving patients at Day 180 post-transplant divided by number of patients undergone transplantation.
From transplant up to Day 180 post-transplant

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.
City of Hope Medical Center

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.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anna Pawlowska, MD, City of Hope Medical Center

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.
August 16, 2005

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.
November 11, 2009

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 28, 2024

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).
October 19, 2007

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.
October 19, 2007

First Posted (Estimated)

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.
October 22, 2007

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.
June 14, 2024

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.
June 4, 2024

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.
June 1, 2024

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.
  • 02165
  • P30CA033572 (U.S. NIH Grant/Contract)
  • CHNMC-02165
  • CDR0000570249 (Registry Identifier: NCI PDQ)

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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