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Acute Bilineal LeukemiaPhase 1NCT03807063

Rivogenlecleucel Donor Lymphocyte Immunotherapy in Treating Patients With Recurrent Blood Cancers After Stem Cell Transplant

A Phase 1 study testing Rivogenlecleucel and Rimiducid in people with Acute Bilineal Leukemia and Myelodysplastic/Myeloproliferative Neoplasm, run by Fred Hutchinson Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

This phase I trial studies the side effects and best dose of rivogenlecleucel, and how well it works, in treating patients with blood cancer that has come back (recurrent) after stem cell transplant. Donor T-cell therapy (rivogenlecleucel) may help control transplant-related infections after stem cell transplant. Read more about this study

Who is it for?
Ages 12 months and older
What is being tested?
Rivogenlecleucel and Rimiducid
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
2 Jan 2020to 31 Dec 2021
Phase
Phase 1

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 12 months and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Original HCT donor: The most recent transplant was from a related or unrelated donor with an allele-level match to the recipient at HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 (10/10) or with a single antigen or allele mismatch (9/10), or with one or two umbilical cord blood units that are individually antigen-level matched to the recipient in at least 4 of 6 HLA loci (HLA-A, -B, -DRB1).
  • Graft source: The most recent transplant (and any previous allotransplant) was from mobilized peripheral blood stem cells and/or bone marrow and/or umbilical cord blood.
  • Transplant number: The relapse occurred after a 1st, 2nd or 3rd allogeneic HCT.
  • Diseases: The subject relapsed or progressed with the same or related disease which prompted the previous allogeneic HCT.
  • Leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], chronic myelogenous leukemia [CML], chronic lymphocytic leukemia [CLL], chronic myelomonocytic leukemia [CMML], blastic plasmacytoid dendritic cell, biphenotypic, bilineage)
  • Myelodysplasia
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  • Myeloproliferative neoplasm
  • Myelodysplasia/myeloproliferative neoplasms (including "unclassified").
  • For subjects with persistent or relapsed acute B-cell lymphoblastic leukemia, the subject must have previously received a chimeric antigen receptor (CAR) T cell product and blinatumomab at any point (not necessarily to treat the current relapse or after the current allogeneic transplant), unless the subject is ineligible for a commercially-available CAR T cell product or blinatumomab or declines those treatments.
  • Relapse stage: The disease stage may be ascertained any time after engraftment of the original donor cells, where engraftment is defined as the first of 3 consecutive days of absolute neutrophil count >= 500/uL unsupported by granulocyte-colony stimulating factor (G-CSF) within the preceding 5 days. (Note that eligibility for the protocol does not require an ANC > 500/uL at the time of enrollment.) Subjects with any of the following disease stages are eligible for this protocol:
  • Morphologic disease persistence or relapse (defined as >= 5% bone marrow blasts in a bone marrow aspirate or biopsy, and/or the presence of circulating blasts detected by automated differential or review of the peripheral blood film and confirmed to be malignant, and/or >= 5% bone marrow blasts with aberrant immunophenotype consistent with malignancy detected by flow cytometry of blood or marrow)
  • Extramedullary disease persistence or relapse (e.g., granulocytic sarcoma, leukemia cutis)
  • A new hematologic malignancy related to the prior transplant indication (such as AML arising from myelodysplastic syndrome [MDS] or ALL arising from mixed lineage leukemia [MLL]-rearranged AML) as per above
  • Subject may have received prior DLI and/or prior genetically-modified DLI such as CAR-T cells and/or prior chemotherapy other than purine analogues to treat minimal residual disease (MRD) or morphologic/clinical relapse or disease persistence but must have had relapse as defined at some point after the most recent HCT to be enrolled on this study.
  • Adequate HCT donor chimerism as indicated by original-donor T cell chimerism (from the most recent HCT) in peripheral blood >= 50%. In the case of double umbilical cord transplant, one of the cord donors should constitute >= 50% of the peripheral blood T cells.
  • For subjects who received genetically-modified T cells such as CAR-T cells or antigen-specific T-cell receptor (TCR) T cells, the non-engineered, polyclonal T cells must constitute at least 50% of total peripheral blood T cells.
  • Performance status: Karnofsky or Lansky performance status (PS) >= 80% or Eastern Cooperative Oncology Group (ECOG) PS 0-1.
  • Capable of giving informed consent, if the subject is 18 years of age or older. A parent or legal representative will be asked to consent for patients young than 18 years old.
  • DONOR: The donor must be available to undergo apheresis at the Seattle Cancer Care Alliance, South Lake Union site or at Bloodworks Northwest.
  • DONOR: The donor must be suitable for medical reasons to donate according to institutional Standard Practice Guidelines and National Marrow Donor Program (NMDP) guidelines, including the absence of transmissible infections (hepatitis A, B, HIV, HTLV I/II, syphilis, West Nile virus [WNV] and Chagas disease).
  • DONOR: The donor must not be homozygous to the recipient at an HLA allele that is common to recipient and donor. (Homozygosity at antigenic resolution is permitted.) Therefore, people who are homozygous at any HLA allele will be excluded.
  • DONOR: The donor may not knowingly be related to a subject on this study by blood (e.g., sibling, parent, child, cousin). This is to prevent "coercive recruitment" of donors.
  • DONOR: The donor must be 18-50 years old.
  • DONOR: Capable of giving informed consent.
  • DONOR: Not pregnant or breastfeeding at the time of apheresis.
  • DONOR: Not on any prescription medications other than birth control pills or vitamins.
  • DONOR: The donor must be cytomegalovirus (CMV) seronegative at the time of screening. For the product to be banked, the CMV polymerase chain reaction (PCR) done on the day of apheresis must be negative.

Who cannot join

  • Subjects who currently have >= grade 1 acute GVHD or any chronic GVHD manifestation beyond pre-existing ocular or oral sicca or pre-existing sclerosis.
  • Subjects with oral or ocular sicca attributable to prior chronic GVHD should be excluded if there are other signs of active GVHD such as eosinophilia not explained by other causes (e.g. recurrent malignancy, medication).
  • Inability to have their dose of corticosteroids tapered to =< 0.25 mg/kg/day prednisone-equivalent for a minimum of 7 days prior to BPX-501 cell infusion. This determination will be made by the subject's treating physician (who is managing the subject's GVHD), documented in a clinical note, and verified by the protocol principal investigator (Pl).
  • Inability to stop all non-steroid immunosuppressive drugs (excepting beclomethasone, budesonide, topical skin corticosteroids, topical tacrolimus, Restasis eye drops, or low doses of glucocorticoids and/or mineralocorticoids given for adrenal insufficiency) for at least 2 weeks without development of grade 1 or greater acute GVHD according to the modified Keystone and NIH GVHD Morbidity Scales.
  • The use of purine analogue chemotherapy (including pentostatin), alemtuzumab, anti-thymocyte globulin, anti-lymphocyte globulin, total body irradiation, and total lymphoid irradiation at any time after infusion of the index HCT graft. All other debulking protocols and patients who received any form of ex-vivo T-cell depleted graft should be cleared by the protocol PI before confirming subject eligibility for this trial.
  • Central nervous system (CNS) leukemia (including leukemia detectable in the cerebrospinal fluid and/or solid chloromas and/or leptomeningeal leukemia) that has not cleared with radiation, intrathecal or systemic therapy.
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  • Inadequate cardiac function defined by left ventricular ejection fraction (LVEF) < 40%.
  • Inadequate pulmonary function defined by any one of the following: forced expiratory volume in one second (FEV1), forced vital capacity (FVC), or corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 40% predicted, or peripheral capillary oxygen saturation (SpO2) < 92% on room air.
  • Direct bilirubin > 3 x upper limit of normal.
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5 X upper limit of normal.
  • Creatinine > 2 X upper limit of normal for age or on dialysis.
  • Concurrent active malignancy other than the malignancy under treatment with BPX-501.
  • Uncontrolled infection, including no invasive fungal infection during the acute antifungal treatment phase (secondary prophylaxis for fungal infection is permitted) and no viral respiratory tract infection that has not cleared as evidenced by a negative nasopharyngeal aspirate or nasopharyngeal swab.
  • Positive for human immunodeficiency virus (HIV), chronic hepatitis B, chronic hepatitis C, or human T-lymphotropic virus (HTLV) pre-transplant (To continue on study, this testing also needs to be confirmed negative within 30 days pre-DLI).
  • Fertile men and women unwilling to use contraceptives before, during, and for 4 months after BPX-501 infusion.
  • Pregnancy: For females of childbearing potential, a pregnancy test is required at enrollment and must be confirmed negative within 7 days before BPX-501 T cell infusion.
  • Medical or psychological conditions present within 30 days prior to enrollment that would make the subject unsuitable for cell therapy or for research trial participation at the discretion of the PI.

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: Phase I Trial With "Off-The-Shelf" Third-Party BPX-501 Donor Lymphocyte Immunotherapy to Treat Persistence or Relapse of Hematologic Malignancies After Allogeneic Stem Cell Transplantation

This phase I trial studies the side effects and best dose of rivogenlecleucel, and how well it works, in treating patients with blood cancer that has come back (recurrent) after stem cell transplant. Donor T-cell therapy (rivogenlecleucel) may help control transplant-related infections after stem cell transplant.

Read the detailed description

This is a dose-escalation study of rivogenlecleucel.

Each subject may receive up to 3 doses of rivogenlecleucel intravenously (IV), at intervals of no less than 28 days. Subjects meeting protocol-specified severity criteria for acute GVHD, chronic GVHD, cytokine release syndrome (CRS), prolonged aplasia, or encephalopathy will be treated with rimiducid infusion(s).

After completion of study treatment, patients are followed up every 6 months for 5 years and then annually for 10 years.

Being tested
Rivogenlecleucel, Rimiducid
Medical subject headings
Myelodysplastic-Myeloproliferative Diseases, Myeloproliferative Disorders, Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Blastic Plasmacytoid Dendritic Cell Neoplasm, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

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

  • RivogenlecleucelBiological

    Also called Allogeneic T-Lymphocytes BPX-501, BPX-501

    Given IV

  • RimiducidDrug

    Also called AP1903

    Given IV

Study groups in NCT03807063
Study groupRoleWhat they receive
Treatment (rivogenlecleucel)ExperimentalEach subject may receive up to 3 IV infusions of rivogenlecleucel at intervals no less than 28 days apart. Subjects who meet protocol-specified severity criteria for acute GVHD, chronic GVHD, cytokine release syndrome (CRS), prolonged aplasia or encephalopathy will be treated with rimiducid infusion(s).
Receives: Biological: Rivogenlecleucel; Drug: Rimiducid

What is being measured

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

  1. Global incidence of grade II-IV acute graft versus host disease (GVHD) requiring rimiducid treatment

    Will be reported, and 95% confidence intervals will be calculated. The global incidence of grade II-IV acute GVHD (requiring rimiducid or not) will also be reported.

    Measured: 1 year after last rivogenlecleucel infusion

  2. Dose-limiting toxicity (DLT) of BPX-501

    Will be reported, and 95% confidence intervals will be calculated. The specific DLTs will be reported descriptively.

    Measured: 56 days after last rivogenlecleucel or rimiducid infusion (whichever is later)

Secondary outcomes (4)

  1. Time to neutrophil and platelet recovery

    Will be reported with cumulative incidence curves (with death as a competing risk), for all donor lymphocyte infusions (DLIs) combined and for each separate dose level.

    Measured: 1 year

  2. Time to grade II-IV acute GVHD

    Will be reported with cumulative incidence curves (with death as a competing risk), for all DLIs combined and for each separate dose level.

    Measured: 1 year

  3. Disease response

    Descriptive, due to the expected heterogeneity of enrolled subjects

    Measured: 1 year

  4. Survival

    Descriptive, due to the expected heterogeneity of enrolled subjects

    Measured: 1 year

Timeline

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

  1. First posted16 Jan 2019
  2. Study start2 Jan 2020
  3. Primary completion31 Dec 2020 (estimated)
  4. Study completion31 Dec 2021 (estimated)

Why it stopped: Insufficient funding

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03807063
Sponsor's protocol ID
RG1004457
Other IDs
NCI-2019-00042, 9739, P30CA015704
Status last verified
Aug 2020
First submitted
14 Jan 2019
Last updated
14 Aug 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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