Id-KLH Vaccine + T Cells in Subjects With Myeloma Undergoing Transplant

Randomized Phase II Trial of CD3/CD28 Activated Id-KLH Primed Autologous Lymphocytes in Subjects With Myeloma Undergoing Autologous Transplant

This study will enroll myeloma subjects undergoing autotransplantation. The primary objective of this study is to evaluate whether infusions of Id-KLH primed CD3/CD28 activated autologous lymphocytes mediate a more intense Id-specific immunity than non Id-KLH primed CD3/CD28 activated autologous lymphocytes. There will be 2 arms in the study, one receiving a DLI with non Id-KLH vaccine and one receiving aDLI with Id-KLH vaccine.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: CD3/CD28

Detailed Description

The primary objectives of this study is to evaluate whether infusions of Id-KLH primed CD3/CD28 activated autologous lymphocytes mediate a more intense id-specific immunity than non id-KLH primed CD3/CD28 activated autologous lymphocytes. The secondary objectives of this study is to demonstrate that doses of 1 times 10e10 Id-KLH primed CD3/CD28 autologous lymphocytes can be infused safely and effectively in more than 80 percent of eligible patients, to determine whether Id-KLH primed CD3/CD28 activated autologous lymphocytes and to determine if the presence of Id-specific immunity correlates with disease response.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • University Of Texas, MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

SCREEN #1 (Visit 1) Step 1:

• Diagnosis of symptomatic multiple myeloma.
• Less than 10 months after initiation of systemic therapy.
• One or two lines of induction therapy with commonly used regimens.
• Age greater than or equal to 18 years to less than or equal to 70 years at the time of enrollment.
• IgG paraprotein (not of IgG3 subtype) with a paraprotein peak (M-spike) of ≥0.2 g/dL. Alternatively subjects who have previously stored purified Id-specific protein on other clinical or laboratory protocols.
• Echocardiogram or MUGA with an ejection fraction of 45% or more and no uncompensated congestive heart failure or uncontrolled arrhythmias.
• Adequate pulmonary function as defined by FEV1, FVC and actual or corrected DLCO of 50% or greater of the predicted value for age, sex and size.
• Adequate renal function as defined by creatinine of 2.0 mg/dl or less or a creatinine clearance of 40cc/min or more.
• Adequate hepatic function as defined by a total bilirubin of 2.0 mg/dl or less and AST and ALT less than 2 times upper limit of normal.
• Ability to sign written informed consent.
• Karnofsky performance status of at least 80% or more.
• Negative serum Beta HCG test in women of child bearing potential and agree to use a medically acceptable form of birth control while on the study drugs.

Exclusion:

• Subjects with melphalan-based induction
• Active uncontrolled infection
• HIV+ or active hepatitis B or C as defined by positive viral load or serology.
• Pre-existing autoimmune diseases, with exception of Hashimoto's thyroiditis.
• Concurrent use of systemic steroids at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during Tcell collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of inhaled steroids is permitted as well.
• Prior autologous or allogeneic transplant.

For this study, there will be no exceptions to eligibility granted.

4.2 PRE-VACCINE #1 ASSESSMENT (Visit 3) Step 2

Subjects must meet the following criteria to proceed with vaccination:

• Less than 9 months from randomization.
• Adequate renal function as defined by creatinine of 2.0 mg/dl or less or a creatinine clearance of 40cc/min or more.
• Adequate hepatic function as defined by a total bilirubin of 2.0 mg/dl or less and AST and ALT less than 2 times upper limit of normal.
• Karnofsky performance status of at least 80% or more.
• At least 2 weeks from last chemotherapy.
• Negative serum Beta HCG test in women of child bearing potential.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm A; Arm A will receive the CD3/CD28 activated autologous lymphocytes intravenously and subcutaneous injections of "KLH only" vaccine.	Biological: CD3/CD28; CD3/CD28 activated autologous lymphocytes intravenously
Other: Arm B; Arm B will receive the CD3/CD28 activated autologous lymphocytes intravenously and subcutaneous injections of ID-KLH Vaccine Myeloma Immunoglobulin Idiotype Vaccine (id-KLH vaccine)	Biological: CD3/CD28; CD3/CD28 activated autologous lymphocytes intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Id-specific Immunity	Evaluate whether infusions of Id-KLH primed CD3/CD28 activated autologous lymphocytes mediate a more intense Id-specific immunity than non Id-KLH primed CD3/CD28 activated autologous lymphocytes. RNA was isolated from CD4 and CD8 T cells pre-vaccine, and at day 30, 90 and 180 post-vaccine for gene expression analysis. The Nanostring Human immunology V2 kit, a multiplex assay for 594 genes involved in the human immunology response, was used with an nCounter digital analyzer to quantify immune response gene expression levels. Subjects were considered to have Id-specific immunity if they induced expression of effector (TBX21, KLRG1) and memory (CCL5) associated genes in CD8 T cells in post-vaccine time-points compared to baseline.	180 DAYS

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Ed Stadtmauer, MD, Abramson Cancer Center of the University of Pennsylvania

Publications and helpful links

General Publications

• Qazilbash MH, Saini NY, Cha SC, Wang Z, Stadtmauer EA, Baladandayuthapani V, Lin H, Tross B, Honhar M, Rao SS, Kim K, Popescu M, Szymura S, Zhang T, Anderson A, Bashir Q, Shpall EJ, Orlowski RZ, Levine BL, Kerr N, Garfall A, Cohen A, Vogl DT, Dengel K, June CH, Champlin R, Kwak LW. A randomized phase 2 trial of idiotype vaccination and adoptive autologous T-cell transfer in patients with multiple myeloma. Blood. 2022 Mar 3;139(9):1289-1301. doi: 10.1182/blood.2020008493.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: August 30, 2011
• First Submitted That Met QC Criteria: August 31, 2011
• First Posted (Estimate): September 1, 2011

Study Record Updates

• Last Update Posted (Actual): December 4, 2020
• Last Update Submitted That Met QC Criteria: December 2, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: adult; myeloma; symptomatic multiple myeloma; diagnosis within 12 months of initiation of systemic therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: UPCC 07409