Study of Gene Modified Donor T Cell Infusion in Patients With Recurrent Disease After Allogeneic Transplant

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

A Phase I study of BPX-501 T cell infusion in adults with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant. The treatment consists of increasing doses of BPX-501 T cell infusions to achieve a clinical response. AP1903 will be investigated for the treatment of aGvHD after BPX-501 T cell infusion to determine a dose that can mitigate GvHD and preserve the graft-versus tumor effect.

Condition or disease	Intervention/treatment	Phase
Hematologic Neoplasms	Biological: BPX-501; Drug: AP1903	Phase 1

Detailed Description:

Un-manipulated donor lymphocyte infusion (DLI) is used after stem cell transplantation to treat and prevent relapse, to prevent infections and to establish full donor chimerism. The addition of mature T cells which exhibit a broad repertoire of T cell immunity against viral antigens, as well as against cancer antigens, might provide a clinical benefit. However, an expected side effect of the presence of mature T cells is the potential occurrence of acute graft-versus-host disease (aGvHD). The use of a suicide gene switch which would trigger the initiation of the apoptosis of the alloreactive T cells by the infusion of a drug would represent the potential optimal strategy for restoring early immunity with a built in "safety switch" against GvHD side effects. Evidence has emerged that low-dose DLI followed by dose escalation can achieve higher clinical response rate with lower GvHD occurrence. Optimization of DLI dose and schedule as well as strategies of donor T-cell manipulation may lead to the consistent ability to separate GvHD from GvT (graft-versus-tumor) activity and improve the safety of DLI treatment. Our strategy is to infuse escalating doses of manipulated T cells (from the same donor who provided the original hematopoietic stem cell graft) in adults with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant to accelerate immune reconstitution thus improving graft versus leukemic effect while reducing the severity of GvHD.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	24 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase I/II Study of Donor BPX-501 T Cell Infusion for Adults With Recurrent or Minimal Residual Disease Hematologic Malignancies Post-Allogeneic Transplant
Study Start Date :	July 2016
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	December 2020

Arms and Interventions

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Arm	Intervention/treatment
Experimental: BPX-501 and AP1903; All subjects will receive 3 cycles of BPX-501 T cell infusions at escalating dose levels (DL). DL1 on Day 0, DL2 on Days 30 and 60. The first dose of BPX-501 T cells will occur ≥30 days after hematopoietic stem cell transplant (HSCT). Two doses of AP1903 ( 0.1 mg/kg and 0.4 mg/kg) will be investigated for the treatment of aGvHD after BPX-501 T cell infusion.	Biological: BPX-501; Biological: T cells transduced with CaspaCIDe suicide gene Drug: AP1903; AP1903 administered to treat GVHD; Other Name: Rimiducid

Outcome Measures

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Primary Outcome Measures :

1. Adverse events [ Time Frame: 2 years ]
   Number of adverse events after BPX-501 as a measure of safety

Secondary Outcome Measures :

1. Adverse events [ Time Frame: 48 hours ]
   Number of adverse events after AP1903 as a measure of safety

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Clinical diagnosis of one of the following:

   1. leukemia
   2. myelodysplasia
   3. lymphoma
   4. multiple myeloma
   5. Other high-risk hematologic malignancies eligible for stem cell transplantation per institutional standard

2. Recurrent disease that presents >100 days after, or minimal residual disease (MRD) that presents > 30 days after either:

   1. Matched related HSCT
   2. Mismatched related HSCT
3. Life expectancy >10 weeks;
4. Signed donor and patient/guardian informed consent;
5. A minimum genotypic identical match of 4/8 is required, 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.
6. Performance status: Karnofsky/Lansky score > 50%.

7. Subjects with adequate organ function as measured by:

   1. Bone marrow: > 25% donor T-cell chimerism in peripheral blood, obtained after 3 weeks post-transplant; ANC >1 x 10E9/L
   2. Cardiac: left ventricular ejection fraction at rest must be ≥ 45%
   3. Pulmonary: FEV 1, FVC, DLCO (diffusion capacity) ≥ 50% predicted (corrected for hemoglobin)
   4. Hepatic: direct bilirubin ≤ 3 x upper limit of normal, or AST/ALT ≤ 5 x upper limit of normal
   5. Renal: creatinine ≤ 2x of ULN for age

Exclusion Criteria:

1. ≥ Grade II acute GvHD or chronic extensive GvHD due to a previous allograft at the time of screening
2. Active CNS involvement by malignant cells (≤ 2 months from the conditioning)
3. Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings); the principal investigator is the final arbiter of this criterion
4. Positive HIV serology or viral RNA
5. Pregnancy (positive serum or urine βHCG test) or breast-feeding
6. Fertile men or women unwilling to use effective forms of birth control or abstinence for one year after transplantation
7. Bovine product allergy

Contacts and Locations

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Locations

United States, Georgia
BMT Program at Northside Hospital	Recruiting
Atlanta, Georgia, United States, 30342
Contact: Brandy Baker-Garner, RN 404-255-1930 Brandy.Baker-Garner@northside.com
Principal Investigator: Scott R Solomon, MD
United States, Kansas
University of Kansas	Recruiting
Westwood, Kansas, United States, 66205
Contact: Renee Sol rsol@kumc.edu
Principal Investigator: Joseph McGuirk, MD
United States, New York
Roswell Park	Recruiting
Buffalo, New York, United States, 14263
Contact: Heather Werner, BBA, CCRP 716-845-1761 heather.werner@roswellpark.org
Principal Investigator: George Chen, M.D.
Weill Cornell Medical College	Withdrawn
New York, New York, United States, 10065
United States, Oregon
Oregon Health & Science University	Recruiting
Portland, Oregon, United States, 97239
Contact: Chelsea Kline 503-418-0128 kline@ohsu.edu
Principal Investigator: Richard T Maziarz, MD
United States, Tennessee
Vanderbilt University	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Shireen Williams 615-875-6278 shireen.a.williams@vanderbilt.edu
Principal Investigator: Michael Byrne, MD
United States, Texas
UT Southwestern Medical Center	Recruiting
Dallas, Texas, United States, 75390
Contact: Ryan Woelfel, CRC 214-648-5130 ryan.woelfel@utsouthwestern.edu
Principal Investigator: Madhuri Vusirikala, M.D.
United States, Washington
Fred Hutchinson Cancer Research Center	Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Michelle Bouvier 206-667-6993 meb@fhcrc.org
Principal Investigator: Brenda Sandmaier, MD

Sponsors and Collaborators

Bellicum Pharmaceuticals

Investigators

Principal Investigator:	Madhuri Vusirikala, MD	University of Texas

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Bellicum Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02477878 History of Changes
Other Study ID Numbers:	BP-008
First Posted:	June 23, 2015
Last Update Posted:	January 16, 2018
Last Verified:	June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Bellicum Pharmaceuticals:

Adult leukemias and myelodysplasia; Adult lymphomas; Adult multiple myeloma

Additional relevant MeSH terms:

Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Hematologic Diseases