TUMOR-ASSOCIATED ANTIGEN-SPECIFIC CYTOTOXIC T-LYMPHOCYTES FOR MULTIPLE MYELOMA
Conditions
Multiple Myeloma
Conditions: official terms
Multiple Myeloma - Neoplasms, Plasma Cell
Conditions: Keywords
Multiple Myeloma, Cytotoxic T-lymphocytes
Study Type
Interventional
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: TAA-specific CTLs
Type: Biological
Overall Status
Recruiting
Summary
This study is for patients that have a cancer called Multiple Myeloma. This research study uses special immune system cells called tumor associated antigen (TAA)-specific cytotoxic T lymphocytes (CTLs), a new experimental therapy.

The proteins that investigators are targeting in this study are called tumor associated antigens (TAAs). These are cell proteins that are specific to the cancer cell.They either do not show or show up in low quantities by normal human cells. In this study we target five common TAAs called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. On a different protocol, patients have been treated and so far this treatment has shown to be safe.

Investigators now want to try this treatment in patients with multiple myeloma.

These TAA-specific CTLs are an investigational product not approved by the Food and Drug Administration.

The purpose of this study is to find the largest safe dose of TAA-specific CTLs, to learn what the side effects are and to see whether this therapy might help patients with multiple myeloma.
Detailed Description
100ml of blood will be collected from the patient on two to three occasions (up to 300 ml = 60 teaspoons total) over a two month period. Under certain conditions related to the patient's health, the blood may need to be collected using a process called apheresis. Apheresis is the process where blood is passed through a machine that separates out the components of the blood that is needed. The remainder of the blood is then returned to the patient's body.

Investigators will use this blood to grow T cells. They will first grow a special type of cells called dendritic cells which will cause activity in the T cells. Once these are made the investigator will load them with small pieces of protein called peptides taken from the TAAs that they want to target. This helps to train the T cells to kill cells with TAAs on their surface. Then the investigators expand these TAA-specific CTLs.

Additional 30 ml (6 teaspoons) of blood will be collected from the patient to test for infectious viruses.

The cells will be infused by intravenous (IV) infusion into the patient over 10 minutes. The patient may be pretreated with acetaminophen (Tylenol) and diphenhydramine (Benadryl). Initially, two doses of TAA-specific CTLs will be given two weeks apart. The patient's disease will be assessed pre-infusion and then 6 weeks after the second infusion. If after the second infusion there is a decrease in the patient's disease or it remains stable, the patient can receive up to six (6) additional doses of the TAA-specific CTLs at monthly intervals. All of the treatments will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital.

In between the first and second infusions and for 6 weeks after the last infusion, the patient is asked not to receive any other anti-cancer treatments such as radiation therapy or chemotherapy. If they do receive any other therapies in-between the first and second infusion of cells, the patient will be taken off treatment and will not be able to receive the second infusion of cells.

This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dose (1 of 4 different levels) of TAA-specific CTLs. Once that dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 4 dose levels are studied. If the side effects are too severe, the dose will be lowered or the TAA-specific CTL infusions will be stopped.

Before being treated, the patient will receive a series of standard medical tests:

physical exam, blood tests to measure blood cells, kidney and liver function, blood tests to measure the patient's multiple myeloma, measurements of the patient's tumor by routine imaging studies and pregnancy test if the patient is a female who can have children.

The patient will receive standard medical tests when they are getting the infusions and after:blood tests to measure blood cells, kidney and liver function, blood tests to measure the patient's multiple myeloma and imaging study 8 weeks after the 1st CTL infusion.

The investigators will follow the patient up to one year from their last infusion. To learn more about the way the TAA specific CTLs are working in the patient's body, an extra 20-40 mls (4-8 teaspoons) of blood will be taken before each infusion, and at Weeks 1, 2, 4, and 6. Afterwards, blood will be collected at 3, 6, 9, and 12 months after the last infusion. The investigators will use this blood to see how long the TAA-specific CTLs last and to look at the immune response to the cancer.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Procurement Inclusion Criteria

- Any patient, at least 18 yrs old regardless of sex, with a diagnosis of Myeloma after receiving at least one treatment regimen

- Patients with life expectancy greater than or equal to 6 weeks.

- Hgb >8.0 (transfusions allowed).

- Patient able to give informed consent.

Treatment Inclusion Criteria

- Any patient, at least 18 yrs old regardless of sex, with a diagnosis of Myeloma after receiving at least one treatment regimen. If patient has received an autologous or syngeneic SCT they must be >90 days post-transplant (Group A) OR Following autologous or syngeneic SCT (as adjuvant therapy) and <90 days post transplant. (Group B)

- Patients with life expectancy greater than or equal to 6 weeks.

- Pulse oximetry of >93% on room air in patients who previously received radiation therapy

- Patients with a Karnofsky score of greater than or equal to 50

- Patients with bilirubin less than or equal to 2 times upper limit of normal, AST less than or equal to3 times upper limit of normal, and Hgb >8.0 (transfusion allowed).

- Engrafted post transplant (ANC > 500 for at least 3 consecutive days) and ANC > 500 at the time of infusion.

- Patients with a creatinine less than or equal to 2x upper limit of normal for age

- Patients should have been off other investigational therapy for one month prior to entry in this study.

- Patients should have been off conventional therapy for at least 1 week prior to entry in this study.

- Patient able to give informed consent.

- Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom. Females of child-bearing potential must be willing to utilize one of the more effective birth control methods during the study unless female has had a hysterectomy or tubal ligation.

Procurement Exclusion Criteria

- Patients with severe active infection.

- Patients with active HIV infection at time of procurement (can be pending at the time of blood draw)

Treatment Exclusion Criteria

- Patients with severe active infection.

- Patients receiving systemic corticosteroid within 48 hours of CTL infusion

- Pregnant
Location
Houston Methodist Hospital
Houston, Texas, United States
Status: Recruiting
Contact: Rammurti Kamble, MD - 713-441-1450 - RTKamble@houstonmethodist.org
Start Date
April 2015
Completion Date
April 2021
Sponsors
Baylor College of Medicine
Source
Baylor College of Medicine
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page