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Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 2NCT01858740

Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Fludarabine Phosphate and Laboratory Biomarker Analysis in people with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Acute Biphenotypic Leukemia, run by Fred Hutchinson Cancer Center 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 phase II trial studies how well T cell depleted donor peripheral blood stem cell transplant works in preventing graft-versus-host disease in younger patients with high risk hematologic malignancies. Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Fludarabine Phosphate and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
10 Apr 2014to 30 Jul 2023
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 Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:
  • Acute lymphocytic leukemia in first or subsequent remission
  • Acute myeloid leukemia in first or subsequent remission
  • Acute lymphocytic leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3
  • Acute myeloid leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3
  • Refractory anemia with excess blasts (RAEB-1 and RAEB-2)
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  • Chronic myelogenous leukemia with a history of accelerated phase or blast crisis
  • Other acute leukemia (including but not limited to 'biphenotypic', 'undifferentiated' or 'ambiguous lineage' acute leukemia)
  • Patient with a human leukocyte antigen (HLA)-identical (HLA-A, B, C, and ribonucleic acid [RNA] binding motif protein 45 [DRB1] molecularly matched) unrelated donor or related donor capable of donating PBSC
  • DONOR: HLA-matched unrelated donors (HLA-A, B, C, and DRB1 matched based on high-resolution typing) capable and willing to donate PBSC
  • DONOR: HLA-matched related donors >= 18 years and capable and willing to donate PBSC

Who cannot join

  • Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation
  • Patients on other experimental protocols for prevention of acute GVHD
  • Patients who weigh >= 70 kg must be discussed with the principal investigator prior to enrolling on the protocol
  • Patients who are human immunodeficiency virus positive (HIV+)
  • Patients with uncontrolled infections for whom myeloablative hematopoietic stem cell transplant (HCT) is considered contraindicated by the consulting infectious disease physician (upper respiratory tract viral infection does not constitute an uncontrolled infection in this context)
  • Creatinine > 1.5 mg/dl
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  • Cardiac ejection fraction < 45%
  • Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of < 60% predicted; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the oxygen (O2) saturation is < 92% on room air
  • Patients who have liver function test (LFTs) (including total bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >= twice the upper limit of normal should be evaluated by a gastrointestinal (GI) physician unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); if the GI physician considers that HCT on protocol 2660 is contraindicated for that patient the patient will be excluded from the protocol; patients with Gilbert's syndrome and no other known liver function abnormality and patients with reversible drug-related transaminitis do not necessarily require GI consultation and may be included on the protocol
  • Patients with a life expectancy < 3 months from co-existing disease other than the leukemia or RAEB
  • Patients who are pregnant or breast-feeding
  • Fertile patients of child bearing age unwilling to use contraception during and for 12 months post-transplant
  • Patients with a significant other medical conditions that would make them unsuitable for transplant
  • Patients with a known hypersensitivity to tacrolimus
  • DONOR: Donors who are HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection
  • DONOR: Donors who fail eligibility requirements for donation of cells or tissue per section 21 Code of Federal Regulations (CFR) 1271 for donation of a HCT/product (P) will be excluded unless use of the cells complies with 21 CFR 1271.65(b)(iii) (urgent medical need) or with 21 CFR 1271.65(b)(i) (allogeneic use in a first-degree or second-degree relative)
  • DONOR: Unrelated donors donating outside of the United States of America (USA) or Germany

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD in Children

This phase II trial studies how well T cell depleted donor peripheral blood stem cell transplant works in preventing graft-versus-host disease in younger patients with high risk hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy 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 a subset of the T cells from the donor cells before transplant may stop this from happening.

Read the detailed description

OUTLINE:

CONDITIONING REGIMEN: Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -7, receive thiotepa intravenously (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.

TRANSPLANT: Patients undergo CD34+ enriched, CD45RA+ T cell-depleted allogeneic PBSCT on day 0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV continuously or orally (PO) every 12 hours beginning on day -1 and continuing through day 50 with taper. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed up for up to 5 years.

Being tested
Allogeneic Hematopoietic Stem Cell Transplantation, Fludarabine Phosphate, Laboratory Biomarker Analysis, Methotrexate, Peripheral Blood Stem Cell Transplantation
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Leukemia, Biphenotypic, Acute, Blast Crisis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute

What participants receive

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

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called allogeneic stem cell transplantation, HSC, HSCT

    Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IV

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant

    Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

  • T Cell-Depleted Hematopoietic Stem Cell TransplantationBiological

    Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV or PO

  • ThiotepaDrug

    Also called 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa

    Given IV

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation

    Undergo TBI

Study groups in NCT01858740
Study groupRoleWhat they receive
Treatment (CD45RA+ T cell depleted PBSCT)ExperimentalCONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -7, receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: Patients undergo CD34+ enriched, CD45RA+ T cell-depleted allogeneic PBSCT on day 0. POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV continuously or PO every 12 hours beginning on day -1 and continuing through day 50 with taper. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Methotrexate; Procedure: Peripheral Blood Stem Cell Transplantation; Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation; Drug: Tacrolimus; Drug: Thiotepa; Radiation: Total-Body Irradiation

What is being measured

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

  1. Graft Failure

    Graft failure defined as failure to reach ANC of >500/uL for 3 consecutive days by day 28, or irreversible decrease in ANC to <100 after an established donor graft. A reduction in ANC as result of relapse is not considered graft failure

    Measured: Up to 5 years

  2. Time to Discontinuation of Systemic Immunosuppression

    Measure the number of days to discontinuation of systemic immunosuppression (both including and excluding calcineurin inhibitors) in pediatric recipients of CD45RA+ T cell-depleted PBSCT. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome)

    Measured: 5 years post transplant

Secondary outcomes (11)

  1. Time to Platelet Count > 50,000/uL for 3 Days Without Transfusion

    Number of days post-transplant without transfusion where platelet count is >50,000/uL. Measured as the first of three days

    Measured: Up to 5 years

  2. Time to Platelet Count > 20,000/uL for 3 Days Without Transfusion

    Number of days post transplant until platelet count is >20,000/uL for three consecutive days without transfusion, counted as the first of three days

    Measured: Up to 5 years

  3. Time to ANC of > 1,000/uL

    Time (in days) to ANC of > 1,000/uL, counted as the first of three consecutive days post-transplant

    Measured: Up to 5 years

  4. Time to ANC of > 500/uL

    Time (in days) to ANC of > 500/uL, counted as the first of three consecutive days post-transplant

    Measured: Up to 5 years

  5. Occurrence of Chronic GHVD Meeting NIH Criteria and Requiring Systemic Pharmacological Immunosuppression

    Number of patients with chronic GVHD defined using NIH criteria. Incidents requiring only calcineurin inhibitors will not be counted. If patients do not develop cGVHD after transplant but then relapse and then receive a donor lymphocyte infusion or antigen specific T cells as treatment, they will no longer be evaluable for the cGVHD endpoint.

    Measured: Up to 5 years

  6. Acute GVHD Grade III-IV

    Number of patients with acute GVHD grade III-IV

    Measured: Up to day 100

  7. Acute GVHD Grades II-IV

    Number of patients with acute GVHD grades II-IV

    Measured: Up to day 100

  8. Steroid Refractory Acute GVHD

    Presence of steroid refractory acute GVHD within the first 100 days post transplant

    Measured: Up to day 100

  9. Relapse Post-transplant

    Relapse defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology

    Measured: Up to 5 years

  10. Transplant Related Mortality

    Transplant related mortality defined as mortality in any patient for whom there has not been a diagnosis of relapse

    Measured: Up to 5 years

  11. Use of Additional Immune Suppressive Agents to Treat Chronic GVHD

    Use of additional immune suppressive agents to treat chronic GVHD other than first line therapy. First line therapy is considered prednisone and tacrolimus/cyclosporin.

    Measured: Up to 5 years

Timeline

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

  1. First posted21 May 2013 (estimated)
  2. Study start10 Apr 2014
  3. Primary completion30 Jan 2023
  4. Study completion30 Jul 2023

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
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01858740
Sponsor's protocol ID
2660.00
Other IDs
NCI-2013-00958, 2660, 2660.00, K23CA154532, RG9213077, R01HL121568, 2P01CA018029
Status last verified
Mar 2024
First submitted
15 May 2013
Last updated
12 Mar 2024
Data monitoring committee
Yes

Publications

  • Bleakley M, Sehgal A, Seropian S, Biernacki MA, Krakow EF, Dahlberg A, Persinger H, Hilzinger B, Martin PJ, Carpenter PA, Flowers ME, Voutsinas J, Gooley TA, Loeb K, Wood BL, Heimfeld S, Riddell SR, Shlomchik WD. Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease. J Clin Oncol. 2022 Apr 10;40(11):1174-1185. doi: 10.1200/JCO.21.01755. Epub 2022 Jan 10.

    PubMed 35007144

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Fludarabine Phosphate and Laboratory Biomarker Analysis in people with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Acute Biphenotypic Leukemia, run by Fred Hutchinson Cancer Center 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 11 inclusion and 17 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 12 Mar 2024. 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 12 Mar 2024). 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?

Graft Failure (time frame: Up to 5 years). 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 NCT01858740, which also lists 1 linked publication.

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 12 Mar 2024.

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