Trial of ID-Specific Donor Vaccinated Lymphocyte Infusion for Patients With Myeloma Relapsing or Failing to Achieve a Complete Remission After an Allogenic Transplant

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01174082
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 4
• Actual Duration (Months): 79.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if vaccinating a donor with your purified myeloma protein and then injecting it back into you will help your immune system control the multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Myeloma	Biological: KLH Vaccine; Biological: KLH-id Vaccine; Drug: GM-CSF; Procedure: Apheresis; Procedure: Donor Lymphocyte Infusion (DLI)	Phase 2

Detailed Description

A vaccine will be made of tumor protein taken from your plasma (liquid part of the blood) and KLH (a protein designed to increase the immune response of the vaccine). By vaccinating your brother or sister with protein made from the tumor, researchers hope to increase the antitumor effect of the stem cells. KLH is used to help the immune response.

Study Treatment Schedule:

If you are found to be eligible to take part in this study, you and your brother or sister will receive a vaccine with KLH. This research involves various steps. In Step 1, a large sample of your plasma will be collected through a vein using a blood separator device. This plasma will be sent to the MD Anderson GMP lab to prepare the vaccine. It takes about 3 months to create your myeloma-specific vaccine. It takes about 3 months to prepare enough vaccine for the next phases of the study.

In Step 2, your brother or sister will receive the vaccine with KLH as an injection under the skin 8 weeks, 6 weeks, and 2 weeks before collection of his/her lymphocytes (immune fighting cells). After each injection, your brother or sister will receive an injection of a medication called GM-CSF that helps the body's response to the vaccine. GM-CSF is given under the skin near the site of the vaccination every day for 4 days, starting the day of the vaccination.

In Step 3, your brother or sister will have apheresis. During apheresis, their blood is passed through a "cell separator" and the lymphocytes (immune fighting cells) are collected. A portion of these cells will be given to you on this day. You will get these cells through a vein while the remainder is stored and frozen for research and/or use later on if you fail to respond to the first infusion.

In Step 4, you will receive the vaccine with KLH. It will be given under the skin immediately after you get the infusion of donor cells, and again 4 and 8 weeks after the lymphocyte infusion. After each vaccine, you will receive an injection of a medication called sargramostim (GM-CSF) that helps the body's response to the vaccine. GM-CSF is given under the skin near the site of the vaccination every day for 4 days, starting the day of the vaccination.

If after 6 months you are not responding to the vaccine, you will be allowed to receive 3 additional vaccines, as long as you did not develop graft versus host disease or any other serious side effects to the first vaccine. The vaccines and follow-up schedule is exactly like the first.

Study Visits:

Within 10 days before you receive the infusion of your donor's cells and within 72 hours before each vaccine injection, the following tests and procedures will be performed:

• Your medical history will be recorded.

• You will have a physical exam, including measurement of your vital signs.

• You will be checked for possible reactions to your treatment, including graft-versus-host disease (GVHD). Infused donor cells may react against your body.

• You will be asked about any side effects you may have had since the first vaccine injection.

• Blood (about 6-12 teaspoons) will be drawn for routine tests and to check your kidney and liver function, as well as the status of your immune system. Part of the blood will be used to test for CMV, hepatitis B, hepatitis C, HIV, HTLV, syphilis, West Nile virus, sickle cell anemia, and Chagas disease. Part of the blood collection will also be used for a pregnancy test for females who are able to have children. To continue to receive infusions of your donor's cells, the pregnancy test must be negative.

• You will have x-rays or bone marrow aspirates and biopsies to assess the response of your disease.

These visits will require 1 day of your time.

Long-Term Follow-Up:

Once a month during Months 3, 6, 12, 18, and 24 months after your last vaccine, the following tests and procedures will be performed:

• Your medical history will be recorded.

• You will have a physical exam, including measurement of your vital signs.

• You will be checked for possible reactions to your treatment, including GVHD.

• Blood (about 6-12 teaspoons) will be drawn to check your kidney and liver, function as well as the status of your immune system. Part of the blood collection will also be used for a pregnancy test for females who are able to have children. To continue to receive infusions of your donor's cells, the pregnancy test must be negative.

• You will have a bone marrow biopsy and aspiration. It may be repeated more often, if your doctor thinks it is needed.

If you are not able to return to MD Anderson, your study doctor may agree to allow you to have these tests and procedures at your local doctor's office. Your local doctor will need to send the results to research staff at MD Anderson.

Once a year, starting 2 years after you receive the last infusion of your donor's cells, you will be contacted by phone to check on your health status.

Length of Study Participation:

You will be considered off study after 5 years. You will be taken off study at any time if lymphocytes cannot be collected, not enough lymphocytes can be collected, your doctor thinks it is needed, the recipient is not able to receive the vaccine, the study doctor thinks it is in your best interest, you need a treatment that is not allowed while on this study, you are unable to keep appointments, or you have intolerable side effects.

This is an investigational study. The myeloma-specific vaccine is not FDA approved or commercially available, and it has been authorized for use in research only. Up to 10 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of ID-Specific Donor Vaccinated Lymphocyte Infusion for Patients With Myeloma Relapsing or Failing to Achieve a Complete Remission After an Allogenic Transplant
• Actual Study Start Date: Jul 20, 2010
• Actual Primary Completion Date: Feb 23, 2017
• Actual Study Completion Date: Feb 23, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KLH Vaccine (Patient) After DLI on same day, patients receive vaccine according to donor randomization (the same type of vaccine that their donors received).	Biological: KLH Vaccine; Donor: 0.5 cc subcutaneously, 3 times on weeks -8, -6 and -2 prior to lymphocyte collection. Patient: 0.5 cc subcutaneously, 3 times immediately after infusion of donor cells (DLI), and again 4 and 8 weeks post DLI.; Drug: GM-CSF; 250 mcg/m2 subcutaneously daily for 4 days after each vaccine; Other Names: Sargramostim Leukine ; Procedure: Donor Lymphocyte Infusion (DLI); Day 0, infusion to patient of collected donor cells.
Experimental: KLH-id Vaccine (Patient) After DLI on same day, patients receive vaccine according to donor randomization (the same type of vaccine that their donors received).	Biological: KLH-id Vaccine; Donor: 0.5 cc subcutaneously, 3 times on weeks -8, -6 and -2 prior to donor lymphocyte collection. Patient: 0.5 cc subcutaneously, 3 times immediately after infusion of donor cells (DLI), and again 4 and 8 weeks post DLI.; Drug: GM-CSF; 250 mcg/m2 subcutaneously daily for 4 days after each vaccine; Other Names: Sargramostim Leukine ; Procedure: Donor Lymphocyte Infusion (DLI); Day 0, infusion to patient of collected donor cells.
Experimental: KLH Vaccine (Donor) Donor Group 1: (non-specific vaccination) vaccinated with KLH only vaccine 0.5 cc subcutaneously, 3 times on weeks -8, -6 and -2 prior to donor lymphocyte collection.	Biological: KLH Vaccine; Donor: 0.5 cc subcutaneously, 3 times on weeks -8, -6 and -2 prior to lymphocyte collection. Patient: 0.5 cc subcutaneously, 3 times immediately after infusion of donor cells (DLI), and again 4 and 8 weeks post DLI.; Drug: GM-CSF; 250 mcg/m2 subcutaneously daily for 4 days after each vaccine; Other Names: Sargramostim Leukine ; Procedure: Apheresis; Day 0 (day of lymphocyte collection) donors undergo a steady state pheresis to obtain lymphocytes.
Experimental: Vaccine KLH-id (Donor) Donor Group 2: (myeloma specific vaccination) vaccinated with KLH-id vaccine 0.5 cc subcutaneously, 3 times on weeks -8, -6 and -2 prior to donor lymphocyte collections.	Biological: KLH-id Vaccine; Donor: 0.5 cc subcutaneously, 3 times on weeks -8, -6 and -2 prior to donor lymphocyte collection. Patient: 0.5 cc subcutaneously, 3 times immediately after infusion of donor cells (DLI), and again 4 and 8 weeks post DLI.; Drug: GM-CSF; 250 mcg/m2 subcutaneously daily for 4 days after each vaccine; Other Names: Sargramostim Leukine ; Procedure: Apheresis; Day 0 (day of lymphocyte collection) donors undergo a steady state pheresis to obtain lymphocytes.

Outcome Measures

Primary Outcome Measures

1. The Rate of Partial Response(PR) and Complete Response(CR) in Patients Receiving DLI From an ID-specific Vaccinated Donor [DLI up to 5 years post DLI]

   PR defined as 50% reduction disease including serum monoclonal paraprotein and CR defined as absence of original monoclonal paraprotein in serum and urine.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Recipient: Patient with IgG1, IgG2, or IgG4 Multiple Myeloma who has received or planning to receive an allogeneic progenitor cell transplant from a HLA compatible related donor (either 6/6 or 5/6 related donor).

2. Recipient: Have evidence of persistent or relapsing disease as demonstrated by persistent serum peak (by either standard protein electrophoresis, immune fixation or free light chain assays) or marrow infiltration. Serum peak must be greater or equal than 0.2 gm/dl and represent more than 70% of the specific immunoglobulin subtype. Patients who have adequate amount of monoclonal idiotype protein previously cryopreserved on prior departmental laboratory protocols are also eligible to be registered for vaccine production using the cryopreserved samples.

3. Recipient: Able to sign written informed consent.

4. Recipient: Age up to 70 years.

5. Recipient: Zubrod PS >/=2.

6. Recipient: Have no serious organ dysfunction as defined by serum creatinine <2.5 mg/dL, serum bilirubin <3 x upper limit of normal, SGPT <4 x upper limit of normal.

7. Recipient: Negative donor infectious disease panel: Hepatitis B surface antigen (HBsAg), Anti-Hepatitis B core antibody (HBcAb), Anti-Hepatitis C Virus antibody (HCV Ab), Anti-Human Immunodeficiency Virus (HIV) antibody (HIV 1/2 type O Ab), Anti-Human T cell lymphotrophic Virus (HTLV) antibody (HTLV I/II Ab), Rapid Plasma Reagen (RPR), Cytomegalovirus antibody (CMV), HCV/HIV Nucleic Acid Test, West Nile Virus Nucleic Acid Test, Sickledex, T Cruzi AB. Additional tests shall be performed as required to assess the possibility of transmission of other infectious or non-infectious diseases.

8. Recipient: Negative serum Beta HCG test in a women with child bearing potential (not post-menopausal for 12 months or no previous surgical sterilization) and willing to use an effective contraceptive measure while on study. Mothers should not breastfeed during the study.

9. Donor: Able to sign written informed consent and be willing to provide donor lymphocytes.

10. Donor: Age 18 - 75 years

11. Donor: No physical contraindications to lymphocyte collection (i.e. severe atherosclerosis, auto-immune disease, cerebrovascular accident, prior malignancy less than 5 years ago other than non-melanoma skin cancer treated with surgery). Donors with severe atherosclerosis by history will receive a cardiology consult and be judged eligible on a case by case basis.

12. Donor: Negative donor infectious disease panel: Hepatitis B surface antigen (HBsAg), Anti-Hepatitis B core antibody (HBcAb), Anti-Hepatitis C Virus antibody (HCV Ab), Anti-Human Immunodeficiency Virus (HIV) antibody (HIV 1/2 type O Ab), Anti-Human T cell lymphotrophic Virus (HTLV) antibody (HTLV I/II Ab), Rapid Plasma Reagen (RPR), Cytomegalovirus antibody (CMV), HCV/HIV Nucleic Acid test. Additional tests shall be performed as required to assess the possibility of transmission of other infectious or non-infectious diseases.

13. Donor: Negative serum Beta HCG test in a woman with child bearing potential (not post-menopausal for 12 months or no previous surgical sterilization) must use an effective method of contraception until at least 1 month after lymphocyte collection. Mothers should not breastfeed during the study.

Exclusion Criteria:

1. Recipient with IGg3 Multiple Myeloma.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Muzaffar H. Qazilbash, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 6, 2012

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01174082
• Other Study ID Numbers: 2004-0660; NCI-2012-01781
• First Posted: Aug 3, 2010
• Last Update Posted: Jun 1, 2018
• Last Verified: May 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Multiple Myeloma; Vaccine; Lymphocyte Infusion
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Vaccines; Sargramostim

Study Results

Participant Flow

Arm/Group Title	Recipient	Donor
Arm/Group Description	Vaccine + DLI	Vaccine
Period Title: Overall Study
STARTED	1	1
COMPLETED	1	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Recipient	Donor	Total
Arm/Group Description	Vaccine + DLI	Vaccine	Total of all reporting groups
Overall Participants	1	1	2
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	1 100%	2 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1 100%	1 100%	2 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%

Outcome Measures

1. Primary Outcome

Title	The Rate of Partial Response(PR) and Complete Response(CR) in Patients Receiving DLI From an ID-specific Vaccinated Donor
Description	PR defined as 50% reduction disease including serum monoclonal paraprotein and CR defined as absence of original monoclonal paraprotein in serum and urine.
Time Frame	DLI up to 5 years post DLI

Outcome Measure Data

Analysis Population Description

The donor participant was to supply the cell product to manufacturer the vaccine. The donor has no disease and therefore cannot be analyzed for a response.

Arm/Group Title	Recipient	Donor
Arm/Group Description	Vaccine + DLI	Vaccine
Measure Participants	1	0
Count of Participants [Participants]	1 100%	0 0%

Adverse Events

Time Frame	Up to 5 years post start of treatment
Arm/Group Title	Recipient		Donor
Arm/Group Description	KLH vaccine + DLI		KLH vaccine
All Cause Mortality
	Recipient		Donor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/1 (0%)
Serious Adverse Events
	Recipient		Donor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Recipient		Donor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Decreased Platelet	1/1 (100%)		0/1 (0%)
Pancytopenia	0/1 (0%)		1/1 (100%)
Ear and labyrinth disorders
Hearing Loss	1/1 (100%)		0/1 (0%)
Gastrointestinal disorders
Diarrhea	1/1 (100%)		0/1 (0%)
Abd cramping	1/1 (100%)		0/1 (0%)
General disorders
Fatigue	1/1 (100%)		0/1 (0%)
Fever	1/1 (100%)		1/1 (100%)
Chills	0/1 (0%)		1/1 (100%)
Infections and infestations
Infection	1/1 (100%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Bone Pain	0/1 (0%)		1/1 (100%)
Nervous system disorders
Insomnia	1/1 (100%)		0/1 (0%)
Dizziness	1/1 (100%)		0/1 (0%)
Headache	1/1 (100%)		0/1 (0%)
Neuropathy	1/1 (100%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/1 (100%)		0/1 (0%)
Hemoptysis	1/1 (100%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Skin Rash	1/1 (100%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.