Safety Study of Gene Modified Donor T-Cells in Adults With Advanced Hematologic Malignancies

NCT02487459 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: BP-005
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, non-randomized study to evaluate the safety of two planned infusions of BPX-501 T cells after partially mismatched, related (haploidentical) HSCT in adults with hematologic malignancies.

Conditions

Hematologic Malignancies

Keywords

acute lymphoblastic leukemia; acute myeloid leukemia; chronic myeloid leukemia; myelodysplastic syndrome; non-hodgkin lymphoma; hodgkin lymphoma

Outcome Measures

Primary Outcomes (1)

• Adverse events

  Number of adverse events after BPX-501 as a measure of safety

  2 years

Secondary Outcomes (1)

• Adverse events

  48 hours

Study Arms (1)

BPX-501 and AP1903

EXPERIMENTAL

Three cohorts, 3 patients each, will receive two infusions (at the same dose) of BPX-501. If needed to treat aGVHD, a single dose of AP1903 will be administered IV.

Biological: BPX-501; Drug: AP1903

Interventions

BPX-501 BIOLOGICAL

T cells transduced with CaspaCIDe suicide gene

BPX-501 and AP1903

AP1903 DRUG

dimerizer drug administered to treat GVHD

Also known as: Rimiducid

BPX-501 and AP1903

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Patients with one of the life-threatening hematological malignancies:
• Acute lymphocytic leukemia (ALL) in CR1 with high-risk features including adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; greater than 1 cycle to achiever remission or with persistent MRD; ALL in second or greater remission with or without MRD. Acute myeloid leukemia (AML) in CR1 with high-risk features defined as: Greater than 1 cycle of induction therapy required to achieve remission; Preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; Presence of FLT3 mutations or internal tandem duplications; FAB M6 or M7 classification; Adverse cytogenetics, -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 \[\> 3 abnormalities\];
• AML in second or greater remission, primary induction failure and patients with relapsed disease;
• Advanced chronic myeloid leukemia (CML) who have progressed to blast phase or accelerated phase and are in need of a transplant and do not have an HLA matched donor;
• MDS with IPSS intermediate-2 or higher or therapy-related MDS.Hodgkin lymphoma or Non-Hodgkin lymphoma (NHL): relapsed disease where remission duration is less than 1 year, relapse after previous autologous transplant, or failure to achieve CR with chemotherapy.
• Age ≥ 18 years and ≤ 65 years
• Deemed eligible for allogeneic stem cell transplantation
• Lack of suitable conventional donor (i.e. 8/8 related or unrelated donor) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
• HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, and DRBl loci
• A minimum genotypic identical haplotype match of 4/8 is required
• The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, and HLA- DRB1
• Subjects with adequate organs function as measured by:
• Cardiac: Left ventricular ejection fraction at rest must be \>45%
• Pulmonary: FEV 1, FVC, DLCO (diffusion capacity) \> 50% predicted (corrected for hemoglobin); or O2 saturation \> 92% on room air

You may not qualify if:

• HLA 8/8 allele matched (HLA-A,-B,-Cw,-DRBl) related or unrelated donor able to donate;
• Autologous hematopoietic stem cell transplant ≤ 3 months prior to enrollment;
• Prior allogeneic transplantation;
• Active CNS involvement by malignant cells (less than 2 months from the conditioning);
• Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings); the PI is the final arbiter of this criterion;
• Positive HIV serology or viral RNA (≥ Grade III per CTCAE criteria);
• Pregnancy (positive serum or urine βHCG test) or breast-feeding;
• Fertile men or women unwilling to use effective forms of birth control or abstinence for a year after transplantation;
• Bovine product allergy.
• Severe obesity (patient's weight is \>/= 1.5x the donor weight).

Sponsors & Collaborators

• Bellicum Pharmaceuticals: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Hodgkin Disease

Interventions

AP 1903 reagent

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma

Study Officials

• Bellicum Pharmaceuticals

  Bellicum Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 29, 2015
• First Posted: July 1, 2015
• Study Start: July 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: October 5, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)