Chronic Myeloproliferative DisordersPhase 2NCT00589602

T-Cell Depletion, Donor Hematopoietic Stem Cell Transplant (HSCT), and T-Cell Infusions in Treating Patients With Hematologic Cancer or Other Diseases

A Phase 2 study testing peripheral blood lymphocyte therapy, allogeneic hematopoietic stem cell transplantation and peripheral blood stem cell transplantation in people with Chronic Myeloproliferative Disorders and Leukemia, run by The Cleveland Clinic 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

Who is it for?: Ages 18 years and older
Conditions the study is for: Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
What is being tested?: peripheral blood lymphocyte therapy, allogeneic hematopoietic stem cell transplantation and peripheral blood stem cell transplantation
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 1 siteUnited States
Study dates: Jan 2004to Dec 2014
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient actual weight must not be greater than 1.5x their ideal body weight
Cardiac ejection fraction >45%. If less than 45%, a Cardiac consult will be obtained.
A suitably matched unrelated donor that is at least a 7 out of 8 HLA serologic match.
Patient is not pregnant.
FEV 1 and DLCO > 45% predicted on pulmonary function testing.
Serum creatinine <2.0 mg/dl, serum bilirubin <2.0 mg/dl.

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Patient and donor are HIV negative.
Diagnosis of one of the following diseases
Acute myelogenous leukemia
Relapsed disease,
Refractory disease, or
With poor-risk cytogenetics
Acute lymphoblastic leukemia
Relapsed disease,
Refractory disease, or
With poor-risk cytogenetics
Chronic myelogenous leukemia
Persistent disease after at least 6 months of treatment with Imatinib Mesylate (Gleevec)
Myelodysplasia
FAB Classification of RAEB or RAEB-T -Or-
IPSS score >2
Lymphoid malignancies, including non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia and prolymphocytic leukemia
Relapsed or refractory disease after at least 1 prior therapy
Myelofibrosis
Transfusion dependence (RBC's, platelets, or both)
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Transfusion dependent
Myeloproliferative Disorder
Eosinophilic Leukemia
Severe aplastic anemia (<1% corrected reticulocyte count, <30,000 untransfused platelet count, bone marrow biopsy with <15% cellularity)
Plasma cell leukemia
Patients with ET or PV will not be candidates unless their disease has transformed to end stage myelofibrosis or acute leukemia, for which eligibility criteria for myelofibrosis or acute leukemia would apply.
Patient must signed written informed consent.

Who cannot join

Inability to give informed consent
Absence of any of the above mentioned medical conditions
Availability of matched-related donor
History of prior allogeneic BMT

Trial locations and contacts

1 site in 1 country.

United States1 site

Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195

Other trials in United States

About this study

Official title: Phase II Feasibility Study of T-Cell Depletion in Allogeneic Unrelated Bone Marrow Transplantation (MUD ALLO BMT) Followed by Delayed T-Cell Infusions

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When 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. Removing the T cells from the donor cells before transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help destroy any remaining cancer cells (graft-versus-tumor effect).

PURPOSE: This phase II trial is studying T-cell depletion in donor stem cell transplant followed by delayed T cell infusions in treating patients with hematologic cancer or other disease.

Read the detailed description

OBJECTIVES:

Primary

Determine if T-cell depletion of a peripheral blood progenitor cell (PBPC) graft followed by delayed add-backs of defined doses of donor lymphocytes decreases the rate of graft-versus-host disease and its complications in matched unrelated donor (MUD) allogeneic peripheral blood progenitor cell (PBPC) transplantation in patients with hematologic cancers or other diseases.
Determine whether targeted T-cell dosages in the PBPC graft can be achieved in these patients by positive CD34+ selection using the Baxter Inc. Isolex 300i v. 2.5.
Determine the effects of T-cell depletion on the rate of engraftment in these patients.
Develop a matched unrelated donor (MUD) allogeneic transplantation regimen that will decrease overall treatment-related mortality in these patients.

OUTLINE: This is a non-randomized study.

Myeloablative preparative regimen: Patients receive cyclophosphamide IV once daily on days -5 and -4 followed by total body irradiation twice daily on days -3, -2, and -1. Patients also receive tacrolimus on day -1 administered by continuous IV infusion over 24 hours.
Peripheral blood progenitor cell graft transplantation: Patients receive T-cell depleted, peripheral blood progenitor cells (PBPC) by IV infusion on day 0. Beginning 1 day after completion of the PBPC infusion, patients receive filgrastim (G-CSF) subcutaneously once daily until blood counts recover.
Post transplantation T cell add-backs: Patients receive defined doses of donor T cells by IV infusion on days 45 and 100, in the absence of active graft-versus-host disease (GVHD) requiring steroids*.

NOTE: *A T cell add-back may be given in the presence of GVHD, if the investigator considers the risk from relapse or overwhelming viral infection to outweigh the risk of exacerbating GVHD.

Patients will be followed periodically for relapse and survival.

Conditions: Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Malignant Plasma Cell Neoplasms, Myelodysplastic Syndromes, Precancerous/Nonmalignant Condition
Being tested: peripheral blood lymphocyte therapy, allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation, total-body irradiation (TBI)
Keywords: Adult leukemia, lymphoma, myelodysplastic syndromes, plasma cell disorders
Medical subject headings: Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Myelodysplastic Syndromes, Precancerous Conditions

What participants receive

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

peripheral blood lymphocyte therapyProcedure or surgery
Also called T-cell depletion
T-cell depletion will be accomplished using CD34 selection with the Baxter Isolex 300i v. 2.5 device. The desirable T-cell dose will be >0.5 x 105 but <1.0 x 105 CD3+ cells per kg. The targeted CD34 cell dose will be >2 x 106 cells/kg.
allogeneic hematopoietic stem cell transplantationProcedure or surgery
Allogeneic Hematopoietic Stem Cell Transplantation
peripheral blood stem cell transplantationProcedure or surgery
Peripheral blood stem cell transplantation
total-body irradiation (TBI)Radiation
Treatment will be delivered using 6MV photons twice daily for 3 days

Study groups in NCT00589602
Study group	Role	What they receive
T-Cell Depletion Transplant	Experimental	Our protocol is designed to attempt to improve the current results of matched unrelated donor (MUD) allo bone marrow transplant (BMT) and will be a major step towards the introduction and refinement of graft engineering. Our approach will address in a rational fashion all major technical and clinical aspects of MUD allo BMT. Peripheral blood lymphocyte therapy; cyclophosphamide, tacrolimus, peripheral blood stem cell transplantation; total-body irradiation; 'allogeneic hematopoietic stem cell transplantation' Receives: Procedure: peripheral blood lymphocyte therapy; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation (TBI)

What is being measured

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

Treatment-related Mortality (TRM)
The complication rate in matched unrelated donor (MUD) allogeneic bone marrow transplant (allo BMT) is known to be high. Graft failure and severe graft versus host disease (GvHD) are the most significant contributors to treatment related mortality (TRM). This treatment regimen will be considered unacceptable if the number of patients that experience TRM is 55% or greater, and effective if TRM is 33% or less.
Measured: 180 days after transplant

Secondary outcomes (4)

The Rate of Acute Graft Versus Host Disease (GVHD)
Measured: D+100 from transplant
Number of Participants With Duration of Absolute Neutropenia
Measured: D+100 from transplant
Number of Participants Able to Receive T-cell Add Backs
Patients receive defined doses of donor T cells by IV infusion on days 45 and 100, in absence of active graft-versus-host disease (GVHD) requiring steroids.
Measured: through D+100
Number of Participants With Relapse-free Survival
number of patients that were still alive and relapse free
Measured: after 7 years of follow up

Timeline

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

Jan 2004Dec 2014

First posted9 Jan 2008 (estimated)
Study startJan 2004
Primary completionAug 2009
Study completionDec 2014

Why it stopped: slow accrual

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
More trials run by The Cleveland ClinicThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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
Model description: Allogeneic Hematopoietic Stem Cell Transplantation
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00589602
Sponsor's protocol ID: CCF-6501
Other IDs: P30CA043703
Status last verified: Apr 2017
First submitted: 1 Jan 2008
Last updated: 30 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia

All Chronic Myeloproliferative Disorders trials

Study at a glance

From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II Feasibility Study of T-Cell Depletion in Allogeneic Unrelated Bone Marrow Transplantation (MUD ALLO BMT) Followed by Delayed T-Cell Infusions
ClinicalTrials.gov ID: NCT00589602
Acronym / sponsor ID: CCF-6501
Conditions: Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Malignant Plasma Cell Neoplasms, Myelodysplastic Syndromes, Precancerous/Nonmalignant Condition
Keywords: Adult leukemia, lymphoma, myelodysplastic syndromes, plasma cell disorders
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: slow accrual
Enrolment: 13 participants (actual)
Lead sponsor: The Cleveland ClinicUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: Jan 2004
Primary completion: Aug 2009 (actual)
Study completion: Dec 2014 (actual)
First posted: 9 Jan 2008 (estimated)
Results: Posted 30 May 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

PURPOSE: This phase II trial is studying T-cell depletion in donor stem cell transplant followed by delayed T cell infusions in treating patients with hematologic cancer or other disease.

Detailed description

OBJECTIVES:

Primary

Determine if T-cell depletion of a peripheral blood progenitor cell (PBPC) graft followed by delayed add-backs of defined doses of donor lymphocytes decreases the rate of graft-versus-host disease and its complications in matched unrelated donor (MUD) allogeneic peripheral blood progenitor cell (PBPC) transplantation in patients with hematologic cancers or other diseases.
Determine whether targeted T-cell dosages in the PBPC graft can be achieved in these patients by positive CD34+ selection using the Baxter Inc. Isolex 300i v. 2.5.
Determine the effects of T-cell depletion on the rate of engraftment in these patients.
Develop a matched unrelated donor (MUD) allogeneic transplantation regimen that will decrease overall treatment-related mortality in these patients.

OUTLINE: This is a non-randomized study.

Myeloablative preparative regimen: Patients receive cyclophosphamide IV once daily on days -5 and -4 followed by total body irradiation twice daily on days -3, -2, and -1. Patients also receive tacrolimus on day -1 administered by continuous IV infusion over 24 hours.
Peripheral blood progenitor cell graft transplantation: Patients receive T-cell depleted, peripheral blood progenitor cells (PBPC) by IV infusion on day 0. Beginning 1 day after completion of the PBPC infusion, patients receive filgrastim (G-CSF) subcutaneously once daily until blood counts recover.
Post transplantation T cell add-backs: Patients receive defined doses of donor T cells by IV infusion on days 45 and 100, in the absence of active graft-versus-host disease (GVHD) requiring steroids*.

NOTE: *A T cell add-back may be given in the presence of GVHD, if the investigator considers the risk from relapse or overwhelming viral infection to outweigh the risk of exacerbating GVHD.

Patients will be followed periodically for relapse and survival.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Allogeneic Hematopoietic Stem Cell Transplantation

Arm	Type	Receives
T-Cell Depletion Transplant	Experimental	Procedure: peripheral blood lymphocyte therapy, Procedure: allogeneic hematopoietic stem cell transplantation, Procedure: peripheral blood stem cell transplantation, Radiation: total-body irradiation (TBI)Our protocol is designed to attempt to improve the current results of matched unrelated donor (MUD) allo bone marrow transplant (BMT) and will be a major step towards the introduction and refinement of graft engineering. Our approach will address in a rational fashion all major technical and clinical aspects of MUD allo BMT. Peripheral blood lymphocyte therapy; cyclophosphamide, tacrolimus, peripheral blood stem cell transplantation; total-body irradiation; 'allogeneic hematopoietic stem cell transplantation'

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (33 listed)

Patient actual weight must not be greater than 1.5x their ideal body weight
Cardiac ejection fraction >45%. If less than 45%, a Cardiac consult will be obtained.
A suitably matched unrelated donor that is at least a 7 out of 8 HLA serologic match.
Patient is not pregnant.
FEV 1 and DLCO > 45% predicted on pulmonary function testing.

Key exclusion criteria (4 listed)

Inability to give informed consent
Absence of any of the above mentioned medical conditions
Availability of matched-related donor
History of prior allogeneic BMT

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
peripheral blood lymphocyte therapyAlso: T-cell depletionT-cell depletion will be accomplished using CD34 selection with the Baxter Isolex 300i v. 2.5 device. The desirable T-cell dose will be >0.5 x 105 but <1.0 x 105 CD3+ cells per kg. The targeted CD34 cell dose will be >2 x 106 cells/kg.	Procedure or surgery	T-Cell Depletion Transplant
allogeneic hematopoietic stem cell transplantationAllogeneic Hematopoietic Stem Cell Transplantation	Procedure or surgery	T-Cell Depletion Transplant
peripheral blood stem cell transplantationPeripheral blood stem cell transplantation	Procedure or surgery	T-Cell Depletion Transplant
total-body irradiation (TBI)Treatment will be delivered using 6MV photons twice daily for 3 days	Radiation	T-Cell Depletion Transplant

Primary outcome

Treatment-related Mortality (TRM)
Time frame: 180 days after transplant
The complication rate in matched unrelated donor (MUD) allogeneic bone marrow transplant (allo BMT) is known to be high. Graft failure and severe graft versus host disease (GvHD) are the most significant contributors to treatment related mortality (TRM). This treatment regimen will be considered unacceptable if the number of patients that experience TRM is 55% or greater, and effective if TRM is 33% or less.

4 secondary outcomes

The Rate of Acute Graft Versus Host Disease (GVHD)
Time frame: D+100 from transplant
Number of Participants With Duration of Absolute Neutropenia
Time frame: D+100 from transplant
Number of Participants Able to Receive T-cell Add Backs
Time frame: through D+100
Number of Participants With Relapse-free Survival
Time frame: after 7 years of follow up

Results and safety

Results posted to the registry on 30 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
T-Cell Depletion Transplant	13	12

Primary outcome: Treatment-related Mortality (TRM)

Time frame: 180 days after transplant. Number. Unit: participants

Measure	T-Cell Depletion Transplant n = 12
Value	8

Population analysed: Patients that received treatment

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events data was over the course of the study for approximately 7 years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
T-Cell Depletion Transplant	9 of 12 (75%)	12 of 12 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Chronic Myeloproliferative Disorders

RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Brian J. Bolwell, MD study chair

The Cleveland Clinic

Jarek Maciejewski, MD, PhD principal investigator

The Cleveland Clinic

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 33 inclusion and 4 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 30 May 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 30 May 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?

Treatment-related Mortality (TRM) (time frame: 180 days after transplant). 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 NCT00589602.

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 30 May 2017.