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

Primary Purpose

Multiple Myeloma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

CD3/CD28

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring adult, symptomatic multiple myeloma, myeloma, diagnosis within 12 months of initiation of systemic therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Abramson Cancer Center of the University of Pennsylvania
University of Texas, MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Arm A

Arm B

Arm Description

Arm A will receive the CD3/CD28 activated autologous lymphocytes intravenously and subcutaneous injections of "KLH only" vaccine.

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01426828

First Posted

August 30, 2011

Last Updated

December 2, 2020

Sponsor

University of Pennsylvania

1. Study Identification

Unique Protocol Identification Number

NCT01426828

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

August 2011 (undefined)

Primary Completion Date

June 2016 (Actual)

Study Completion Date

December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

adult, symptomatic multiple myeloma, myeloma, diagnosis within 12 months of initiation of systemic therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Other

Arm Description

Arm A will receive the CD3/CD28 activated autologous lymphocytes intravenously and subcutaneous injections of "KLH only" vaccine.

Arm Title

Arm B

Arm Type

Other

Arm Description

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)

Intervention Type

Biological

Intervention Name(s)

CD3/CD28

Intervention Description

CD3/CD28 activated autologous lymphocytes intravenously

Primary Outcome Measure Information:

Title

Participants With Id-specific Immunity

Description

Time Frame

180 DAYS

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ed Stadtmauer, MD

Organizational Affiliation

Abramson Cancer Center at Penn Medicine

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Muzaffar H. Qazilbash, MD

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Abramson Cancer Center of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

University of Texas, MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34521108

Citation

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.

Results Reference

derived

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

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