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Acute Myelogenous LeukemiaPhase 2NCT00571662

Safety and Efficacy of Pentostatin and Low Dose TBI With Allogenic Peripheral Blood Stem Cell Transplant

A Phase 2 study testing Pentostatin, Total-body irradiation (TBI) and Cyclosporine A (CsA) in people with Acute Myelogenous Leukemia and Acute Lymphocytic Leukemia, run by University of Nebraska at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a continuation of a pilot study which is now regarded as a phase II trial with a plan to enroll an additional 40 patients (20 related and 20 unrelated donor transplants) with hematological malignancy assessing the safety and efficacy of a minimally myelosuppressive regimen with pentostatin and low-dose total… Read more about this study

Who is it for?
Ages 19 to 75 years
What is being tested?
Pentostatin, Total-body irradiation (TBI) and Cyclosporine A (CsA)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
76 participants
Where
1 siteUnited States
Study dates
8 Dec 2000to 30 Dec 2008
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 19 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 19-75 years
  • Patients who relapse after autologous stem cell transplantation.
  • Patients who are candidates for an autologous or conventional allogeneic stem cell transplantation from a disease standpoint but who do not qualify functionally (from the point of view of organ function, or performance status) for a myeloablative protocol.
  • Any patient, where in the opinion of the primary treating oncologist, nonmyleoablative therapy would be the treatment option in the best patients interest providing the patient fits all other eligibility criteria for this protocol.
  • Identification of a matched related or unrelated stem cell donor
  • Diseases:
Show all 12Show fewer
  • Acute myelogenous leukemia first complete remission with high-risk cytogenetics>second complete remission minimal residual disease (<10% blasts). Acute lymphocytic leukemia first complete remission with high-risk cytogenetics >second complete remission minimal residual disease (<10% blasts). Chronic myelogenous leukemia first chronic phase, accelerated phase (<10% blasts)blast phase with minimal residual disease (<10% blasts)second chronic phase. Chronic lymphocytic leukemia recurrence after the front line regimen (related donor transplant), chemorefractory disease (unrelated donor transplant),T-CLL in partial remission or any minimal residual disease. Myelodysplastic syndromes refractory anemia with or without ringed sideroblasts,RAEB, RAEB-T, and CMML (< than 10% blasts). both in peripheral blood and bone marrow
  • Multiple myeloma - after receiving at least one regimen of prior chemotherapy
  • Non-Hodgkin's Lymphomas:
  • Small Lympho(plasma)cytic Lymphoma (B-SLL, B-LPL): recurrence after a front line regimen (related donor transplant), or chemorefractory disease (related or unrelated donor transplant). Follicular Low-Grade Lymphoma, Marginal Zone Lymphomas (splenic, nodal, or extranodal/MALT type): chemorefractory disease or > 2 prior regimens. Mantle Cell Lymphoma: first complete or partial remission, refractory disease, or failed prior ASCT. Diffuse Large B-cell Lymphoma, Follicular Large cell Lymphoma, Peripheral T-cell Lymphoma, Anaplastic Large Cell Lymphoma: refractory disease, or failed prior ASCT. Burkitt or Acute Lymphoblastic Lymphomas: high-risk disease in remission, chemosensitive persistent or recurrent disease. Cutaneous T-cell Lymphomas: (Mycosis Fungoides, Sezary Syndrome): chemorefractory disease of > 2 prior regimens
  • Hodgkins Disease: refractory or persistent disease and not candidate for ASCT, or failed prior ASCT.
  • Peripheral T-cell Lymphoma

Who cannot join

  • Age > 75 years and < 19 years
  • progressive disease within 8 weeks of prior therapy or within 12 weeks after prior autologous stem cell transplantation
  • Active CNS malignancy (patients with known positive CSF cytology or parenchymal lesions visible by CT or MRI)
  • Fertile men or women unwilling to use appropriate contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant
  • Patients who are HIV seropositive
Show all 27Show fewer
  • Active uncontrolled infection or immediate life-threatening condition at the time of enrollment
  • Significant Organ dysfunction:
  • Calculated Creatinine Clearance <55ml/min
  • cardiac ejection fraction <40%, NYHA class II or greater cardiac disease.
  • DLCO < 40% , FEV1/FVC ratio <50% predicted, or receiving supplementary continuous oxygen
  • total bilirubin > 2x upper limit of normal (unless due to Gilberts disease or malignancy), ALT and AST 4x the upper limit of normal
  • Karnofsky score <60%
  • Patients with uncontrolled medical illnesses (e.g., uncontrolled systemic hypertension, diabetes)
  • Donor Inclusion Criteria:
  • HLA genotypically matched relative
  • siblings or first-degree relatives matched at HLA-A, B, or DR loci (6 antigen match) are acceptable donors
  • HLA matched unrelated volunteer donor
  • unrelated donor matched at HLA-A, B, or DR loci (6 antigen match) are acceptable donors
  • One antigen mismatch related or unrelated donor will also be acceptable, molecular typing needs to be used at each H LA-A, B, or DR loci in case of mismatched unrelated donor.
  • Donor Exclusion Criteria:
  • Identical twin
  • Pregnancy
  • HIV positive
  • Serious Allergy to G-CSF
  • Current serious systemic illness
  • Failure to meet the UNMC or NMDP criteria for donors

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Nebraska Medical Center, Section of Oncology/Hematology

    Omaha, Nebraska, 68198

Other trials in United States

About this study

Official title: Allogeneic Peripheral Blood Stem Cell Transplantation With Minimally Myelosuppressive Regimen of Pentostatin and Low-dose Total-body Irradiation

This is a continuation of a pilot study which is now regarded as a phase II trial with a plan to enroll an additional 40 patients (20 related and 20 unrelated donor transplants) with hematological malignancy assessing the safety and efficacy of a minimally myelosuppressive regimen with pentostatin and low-dose total body irradiation (TBI) followed by allogeneic peripheral blood stem cell transplantation (alloPSCT).

Read the detailed description

This is a pilot study which began with a plan to enroll 50 patients (20 related and 30 unrelated donor transplants) with hematological malignancy assessing the safety and efficacy of a minimally myelosuppressive regimen with Pentostatin and low-dose total body irradiation (TBI) followed by allogeneic peripheral blood stem cell transplantation (alloPSCT). Patients with persistent or progressive malignancy after transplantation will be treated with GM-CSF (cytokine therapy) to assess its toxicity and potential therapeutic efficacy. Patients with persistent or progressive disease who fail or do not qualify for the cytokine therapy portion of the study will become candidates for donor leukocyte infusions.

The purpose of this protocol remains a pilot study which is now regarded as a phase II trial with a plan to enroll 40 ADDITIONAL patients (20 related and 20 unrelated donor transplants) with hematological malignancy assessing the safety and efficacy of a modified version of the original preparative regimen of Pentostatin and low-dose total body irradiation (TBI) followed by allogeneic peripheral blood stem cell transplantation (alloPSCT). Patients who fail will become candidates for donor-leukocyte infusion (DLI).

Primary Objectives

  1. To determine the safety of treating hematological malignancies by establishing donor hematopoietic chimerism using pentostatin and low-dose total body irradiation followed by allogeneic peripheral blood stem cell transplantation.
  2. To determine the immunomodulatory effects of pentostatin as part of the conditioning regimen for allogeneic peripheral blood stem cell transplantation.

Secondary Objectives

  1. To determine the incidence of infections after using a minimally myelosuppressive conditioning regimen.
  2. To determine the kinetics of hematological and immunological reconstitution after allotransplantation with a minimally myelosuppressive conditioning regimen.
  3. To determine the incidence of chronic GVHD after using allogeneic peripheral blood stem cell transplantation with a minimally myelosuppressive preparative regimen.
  4. To evaluate the role of the preparative regimen and donor source (related versus unrelated) on inflammatory cytokine profiles.
  5. To evaluate blood and where possible, biopsy specimens for a recently identified nuclear protein (molecular weight 44/46) in mononuclear cells obtained from study subjects.

Interventions, evaluation, and follow up will include:

Pentostatin 4 mg/m^2/d intravenously once a day x 3 days will be administered with 1000 cc NS hydration before and after pentostatin ten days prior to stem cell infusion (days -10, -9, and -8). Total-body irradiation (TBI): TBI 2.0 Gy will be given on day -1. Antiemetics will be given as needed. Patients will receive one liter normal saline over 2 hours pre TBI. A bone marrow biopsy and aspiration with cytogenetics and flow cytometry will be performed on Day +28, Day +70 and 6, 12, 18 and 24 months following the transplant to monitor hematologic recovery. DNA fingerprinting will also be conducted at the same time at 3, 4, 5, 6, 12, 18, and 24 months to determine chimerism.

Being tested
Pentostatin, Total-body irradiation (TBI), Cyclosporine A (CsA), Mycophenolate Mofetil (MMF), G-CSF
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Lymphocytic, Chronic, B-Cell, Myelodysplastic Syndromes, Multiple Myeloma, Lymphoma, Non-Hodgkin, Hodgkin Disease

What participants receive

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

  • PentostatinDrug

    Also called Nipent

    4 mg/m^2 intravenous(IV)once a day(QD)x3days (days -10, -9, -8)

  • Total-body irradiation (TBI)Radiation

    TBI will consist of 2.0 GY at 8-12cGy/min via 6MV photons delivered AP/PA fields, without lung blocks or via lateral fields with lucite compensator along the head and neck region. TLD (thermal luminescent dosimetry) will be used to verify dose uniformity. TBI will be given on day -1.

  • Cyclosporine A (CsA)Drug

    Also called Neoral

    CsA will be given at 2.0 mg/kg intravenous (IV) Q 12hrs on days -1,0,and+1 (total 6 doses) then converted to oral at 2 mg/kg by mouth (PO) twice a day (BID) until day+80, then tapered 10% per week over approximately 3 months if no GVHD for related donor transplants. For unrelated CsA will be given at same dose and schedule until day+100 then tapered by 10% per week if no GVHD

  • Mycophenolate Mofetil (MMF)Drug

    MMF 15 mg/kg by mouth twice a day (PO BID) will be given from day 0-27 then stopped without tapering for related donor transplants. For unrelated donor transplants MMF will be given at same dose until day+40 then tapered over 2months. in absence of GVHD. Doses will be rounded to nearest 250 mg.

  • G-CSFDrug

    Also called Leukine

    10 mcg/kg/day subcutaneously for at least 4 consecutive days.

Study groups in NCT00571662
Study groupRoleWhat they receive
Cohort IExperimentalPentostatin to be administered intravenously on days - 10, -9, and -8 at a dose of 4mg/m2/day
Receives: Drug: Pentostatin; Radiation: Total-body irradiation (TBI); Drug: Cyclosporine A (CsA); Drug: Mycophenolate Mofetil (MMF); Drug: G-CSF

What is being measured

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

  1. Percent of Participants With Chimerism: Full Donor Chimerism Defined as >95% Donor CD3+ Cell in Blood as Assessed by DNA Fingerprinting

    the efficacy of the regimen as determined by engraftment rate and establishment of donor hematopoietic chimerism at day +28 and day +70.

    Measured: days +28 and +70

  2. Toxicity for the Combination of Pentostatin and Low Dose Total Body Irradiation (TBI)

    Measured: Conditioning regimen to count recovery (D + 28 post transplant)

Secondary outcomes (3)

  1. Incidence of Acute and Chronic Graft-versus-host Disease

    Incidence of acute and chronic graft-versus-host disease. Acute GVHD usually occurs during the first three months following transplant. Chronic GVHD usually develops after the third month post-transplant.

    Measured: twice weekly until day 100 up to 1 year post transplant

  2. Responses to Therapy

    event-free and overall survival at 12 months

    Measured: every 6 mo. up to 2 years

  3. Kinetics of Immunologic Reconstitution

    Rate of return of immune cells after allogeneic transplantation

    Measured: at day 100 post transplantation

Timeline

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

  1. First posted12 Dec 2007 (estimated)
  2. Study start8 Dec 2000
  3. Primary completion30 Dec 2008
  4. Study completion30 Dec 2008

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
76 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00571662
Sponsor's protocol ID
0389-00-FB
Status last verified
Oct 2023
First submitted
11 Dec 2007
Last updated
24 Oct 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pentostatin, Total-body irradiation (TBI) and Cyclosporine A (CsA) in people with Acute Myelogenous Leukemia and Acute Lymphocytic Leukemia, run by University of Nebraska 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 12 inclusion and 27 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: finished, as of the sponsor's last update on 24 Oct 2023. 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 17 Nov 2010). 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?

Percent of Participants With Chimerism: Full Donor Chimerism Defined as >95% Donor CD3+ Cell in Blood as Assessed by DNA Fingerprinting (time frame: days +28 and +70). 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?

On the ClinicalTrials.gov record for NCT00571662.

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 24 Oct 2023.

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