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

NCT03807063 | Withdrawn Phase 1 DMC FDA Drug

• 4 other identifiers: RG1004457NCI-2019-000429739P30CA015704
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Bilineal Leukemia; Myelodysplastic/Myeloproliferative Neoplasm; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloproliferative Neoplasm; Recurrent Acute Biphenotypic Leukemia; Recurrent Acute Lymphoblastic Leukemia; Recurrent Acute Myeloid Leukemia; Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Chronic Myelomonocytic Leukemia; Recurrent Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• 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.

  1 year after last rivogenlecleucel infusion

• Dose-limiting toxicity (DLT) of BPX-501

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

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

Secondary Outcomes (4)

• Time to neutrophil and platelet recovery

  1 year

• Time to grade II-IV acute GVHD

  1 year

• Disease response

  1 year

• Survival

  1 year

Study Arms (1)

Treatment (rivogenlecleucel)

EXPERIMENTAL

Each 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).

Biological: Rivogenlecleucel; Drug: Rimiducid

Interventions

Rivogenlecleucel BIOLOGICAL

Given IV

Also known as: Allogeneic T-Lymphocytes BPX-501, BPX-501

Treatment (rivogenlecleucel)

Rimiducid DRUG

Given IV

Also known as: AP1903

Treatment (rivogenlecleucel)

Eligibility Criteria

• Age: 12 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Bellicum Pharmaceuticals: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

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; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

AP 1903 reagent

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Histiocytic Disorders, Malignant; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Elizabeth Krakow

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2019
• First Posted: January 16, 2019
• Study Start: January 2, 2020
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2021
• Last Updated: August 14, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)