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

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.

Inclusion Criteria:

- Weighing >= 40 kg at the time of consent.

- 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 or 2nd allogeneic HCT.

- 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

- 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.

- 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 the following
disease stages are eligible for this protocol:

- Persistent or recurrent minimal residual disease (MRD)

- Morphologic relapse

- Progression of clinically apparent disease that was present at the time of
transplant.

- Karnofsky performance status (PS) >= 80% or Eastern Cooperative Oncology Group (ECOG)
PS 0-1.

- 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.

- Subject may have received prior DLI and/or prior chemotherapy other than purine
analogues to treat MRD or morphologic/clinical relapse or progression but must have
persistent/recurrent MRD or morphologic relapse at the time of enrollment on this
study.

- Subject may have received prior CAR-T cell therapy to treat MRD or
morphologic/clinical relapse or progression but must have persistent/recurrent MRD or
morphologic/clinical relapse or progression at the time of enrollment on this study.
The non-CAR-T cells must constitute at least 50% of total peripheral blood T cells.

- Subject may have received prior antigen-specific T-cell receptor (TCR) T cell therapy
to treat MRD or morphologic/clinical relapse or progression but must have
persistent/recurrent MRD or morphologic/clinical relapse or progression at the time of
enrollment on this study. The non-engineered polyclonal T cells must constitute at
least 50% of total peripheral blood T cells.

- 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.

- DONOR: The donor must be suitable for medical reasons to donate according to Fred
Hutchinson Cancer Research Center (FHCRC) 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.

Exclusion Criteria:

- 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.

- 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.

- 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.

- Fertile men and women unwilling to use contraceptives before, during, and for 4 months
after BPX-501 infusion.

- 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.