CART-19 for Multiple Myeloma

NCT02135406 | Completed Phase 1 DMC

• 1 other identifier: UPCC02413, 817462
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The primary goals: determine the safety, tolerability and engraftment potential of CART-19 T cells in patients undergoing salvage ASCT after early relapse following first ASCT. CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCR(zeta):41BB administered by intravenous infusion using a single infusion of 1-5x108 CART19-transduced T cells on day +2 after autologous stem cell infusion following high-dose melphalan.

Conditions

Multiple Myeloma

Keywords

Adult; 18 years or older; multiple myeloma; poor prognosis; relapsed/progressive disease; within one year of first autologous stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events

  2 years

Study Arms (1)

Multiple Myeloma Patients

EXPERIMENTAL

Adult subjects (18 years or older) with multiple myeloma and with poor prognosis by virtue of having relapsed/progressive disease within one year of first autologous stem cell transplantation.

Biological: CART-19 T cells

Interventions

CART-19 T cells BIOLOGICAL

Multiple Myeloma Patients

Eligibility Criteria

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

You may not qualify if:

• Subjects who have undergone two prior ASCTs as part of a planned tandem ASCT consolidation regimen are eligible.
• Patients in whom first progression is identified between days 366 and 450 (inclusive) after ASCT will be eligible if progression is identified on their first evaluation for progression in this window and if they had not been evaluated between days 270 and 365 for progression. This clause is to account for practice patterns in which patients otherwise doing well are monitored infrequently (every 3-6 months) for relapse after they recover from their first ASCT. This will allow infrequently monitored patients to be included if progression is identified on their "12 month follow-up evaluation" if this appointment happens to be scheduled just outside the 365-day post-ASCT window. N.B.: There is no requirement that patients must enroll within 365 days of prior ASCT, and patients may be treated with other agents, including experimental agents, following relapse/progression after prior ASCT before enrollment on this study.
• Subjects must have received as part of their initial therapy for MM, prior to first ASCT, a regimen containing either bortezomib or lenalidomide.
• Subjects must have a confirmed diagnosis of active MM prior to first ASCT as defined by the IMWG criteria143, with the exception that patients treated for active MM on account of recurrent, complicated infections as the only clinical manifestation or on account of progressive smoldering MM with imminent clinical complications may be included.
• Subjects must have signed written, informed consent. Subjects must be ≥ 18 and \<70 years of age. Subjects must have an anticipated survival of \>100 days after high-dose melphalan.
• Subjects must have adequate vital organ function as defined by the following criteria: Serum creatinine ≤ 2.5 or estimated creatinine clearance ≥30 ml/min and not dialysis-dependent.
• Absolute neutrophil count ≥1000/μl and platelet count ≥50,000/μl. SGOT ≤ 3x the upper limit of normal and total bilirubin ≤ 2.0 mg/dl (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome).
• Left ventricular ejection fraction (LVEF) ≥ 45% Adequate pulmonary function with FEV1, FVC, TLC, DLCO (after appropriate adjustment for lung volume and hemoglobin concentration) ≥40% of predicted values.
• Toxicities from prior therapies must have recovered to grade ≤2 according to the CTC 4.0 criteria or to the subject's prior baseline.
• Subjects must have an ECOG performance status of 0-2, unless a higher performance status is due solely to bone pain.
• Subjects must be willing to comply with the requirements of the RevAssist program if maintenance lenalidomide is planned.
• Subjects must have measurable disease on study entry. Measurable disease may include quantifiable or detectable levels of serum or urine paraprotein. For patients with minimally secretory disease or non-secretory myeloma on study entry, serum free lambda or kappa light chain levels or the serum free light chain ratio may be measured and used for disease monitoring if abnormal. Likewise, for patients with IgA MM in which serum protein electrophoresis is deemed unreliable due to co-migration of normal serum proteins with the paraprotein, elevated total serum IgA levels may be considered measurable disease.
• Subjects must have stored in usable condition for second ASCT, as judged by the principal investigator, ≥3x106 CD34+ cells per kg of body weight (either autologous or syngeneic) stored in at least two bags such that after administration of the minimum dose of 2 x 106 CD34+ cells/kg required on this protocol that a separate aliquot of at least 1 x 106 CD34+ cells/kg remains for rescue infusion in the event of graft failure. Patients with inadequate stem cells stored may still sign consent and undergo a mobilization/collection procedure either before or after apheresis for T cell harvest. If this is required and is undertaken prior to apheresis for T cell harvest, two weeks must elapse between the last day of stem cell collection and apheresis for T cell harvest.
• Table 5 IMWG Criteria for Progression
• One or more of the following criteria must be met:

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Garfall AL, Stadtmauer EA, Hwang WT, Lacey SF, Melenhorst JJ, Krevvata M, Carroll MP, Matsui WH, Wang Q, Dhodapkar MV, Dhodapkar K, Das R, Vogl DT, Weiss BM, Cohen AD, Mangan PA, Ayers EC, Nunez-Cruz S, Kulikovskaya I, Davis MM, Lamontagne A, Dengel K, Kerr ND, Young RM, Siegel DL, Levine BL, Milone MC, Maus MV, June CH. Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. JCI Insight. 2018 Apr 19;3(8):e120505. doi: 10.1172/jci.insight.120505. eCollection 2018 Apr 19.

  PMID: 29669947 DERIVED

• Garfall AL, Maus MV, Hwang WT, Lacey SF, Mahnke YD, Melenhorst JJ, Zheng Z, Vogl DT, Cohen AD, Weiss BM, Dengel K, Kerr ND, Bagg A, Levine BL, June CH, Stadtmauer EA. Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma. N Engl J Med. 2015 Sep 10;373(11):1040-7. doi: 10.1056/NEJMoa1504542.

  PMID: 26352815 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Disease Progression

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Edward Stadtmauer, MD

  Abramson Cancer Center at Penn Medicine

  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: May 8, 2014
• First Posted: May 12, 2014
• Study Start: May 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: January 18, 2018
• Last Updated: June 22, 2023

Record last verified: 2018-02

Locations

US (1)