Th1/Tc1 Immunotherapy Following Stem Cell Transplantation in Multiple Myeloma

NCT01239368 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 11001611-C-0016
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

Background: \- Cancer development is associated with problems in immune system functions, which prevent the body from attacking and destroying the abnormal cells that lead to tumor growth. Research has suggested that certain white blood cells, known as Th1 (type 1 T helper cells) and Th2 T cells (type 2 T helper cells), are affected in individuals with some kinds of cancer -- when the proportion of Th2 cells is greater than Th1 cells, the immune systems ability to fight off the growth of malignant tumors is weakened. Researchers are interested in determining if an infusion of specially modified Th1 cells, in addition to stem cell transplant, is a safe and effective treatment for individuals with forms of multiple myeloma that might not respond well to standard treatments alone. Objectives: \- To determine the safety and effectiveness of the infusion of modified Th1 white blood cells, in conjunction with standard treatment, as a treatment for individuals who have been diagnosed with high-risk forms of multiple myeloma. Eligibility:

• Individuals age 18 to 75 who have been newly diagnosed with high-risk multiple myeloma and who have received no or minimal treatment (Cohort A).
• Individuals age 18 to 75 who have relapsed multiple myeloma, as defined by measurable disease after at least 2 prior treatment regimens. Design:
• Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies. Some participants may also have a bone marrow or other type biopsy to evaluate the state of their disease.
• White blood cells will be collected from the participants through an apheresis procedure, which will collect and separate the white blood cells and return the rest of the blood to the participant.
• The collected cells will be grown and expanded under special conditions in the laboratory and stored frozen until participants receive standard of care treatment for multiple myeloma, including a stem cell transplant.
• Participants will receive an infusion of the modified Th1 cells a few weeks after the transplant, and will remain in the hospital for a few days after receiving the cells to monitor the possible immediate effects of the treatment.
• Participants will have regular follow-up visits to study the long-term effects of the modified Th1 cell infusion.

Conditions

Myeloma, Plasma-Cell; Myeloma-Multiple; Myelomatosis

Keywords

Multiple Myeloma; High Risk; Newly Diagnosed; Adoptive Immunotherapy; Autologous

Outcome Measures

Primary Outcomes (3)

• Number of Patients With an Adverse Event Attributable to the Investigational Therapy

  Participants were assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  2 months

• Number of Participants With Progression Free Survival in Cohort A Th1 (Type 1 T Helper Cells)/Tc1 (T Cytotoxic Cells, Type 1) Rapa Prevention of Relapse

  Progressive disease is assessed by the Consensus of the International Myeloma Working Group criteria and is defined as one or more of the following: Increases of greater or equal to 25% in serum M-component (minimum absolute increase of 0.5 g/dl) or urine M-component (minimum absolute increase of 200mg/24h) or percentage of bone marrow plasma cells (minimum absolute percentage of 10%) or size of bone lesions or new plasmacytoma, or development of hypercalcemia solely attributable to the disease.

  Study completion at 22 months

• Number of Patients Who Developed a Partial Response (PR)+Complete Response (CR) in Cohort B at Any Time Point Post Therapy With PR/CR Being Maintained Until Study Completed

  Patients whose tumors shrunk and were disease free after therapy in cohort B. Partial response and complete response were assessed by the Consensus of the International Myeloma Working Group criteria. Partial response is defined as 50% or greater reduction in serum M-protein and 90% or greater reduction in 24-h urinary M-protein (or to less than 200 mg per 24h), 50% or greater reduction in the size of soft tissue plasmacytomas, if present at baseline, no evidence of progressive or new bone lesions if radiographic studies were performed (X-rays not required in absence of clinical indication). Complete response is defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and 5% or less plasma cells in bone marrow and no evidence of progressive or new bone lesion if radiographic studies were performed. Progressive disease is increases of ≥25% in serum M-component/urine M-component, or size of bone lesions.

  Study completion at 22 months

Secondary Outcomes (2)

• Immune Reconstitution in Recipients of Th1.(T Helper Cell) Rapa Cells.

  Baseline, prior to chemotherapy, and 2 weeks, 1, 2, and 3 months after final T cell infusion

• Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  Date treatment consent signed to last date off study, 81 months and 6 days

Study Arms (2)

Cohort B - Relapsed Multiple Myeloma

EXPERIMENTAL

Th1 (type 1 T helper cells)/Tc1 (T cytotoxic cells, type 1) .Rapamycin (Rapa) for Relapsed Multiple Myeloma

Procedure: Adoptive Immunotherapy; Biological: Th1/Tc1 Rapa Cell Therapy

Cohort A - Prevention of Relapse

EXPERIMENTAL

Th1/Tc1.Rapa Prevention of Relapse

Procedure: Adoptive Immunotherapy; Biological: Rapamycin-Generated Autologous Th1/Tc1 Cells (modified primary human T cells); Biological: Th1/Tc1 Rapa Cell Therapy

Interventions

Adoptive Immunotherapy PROCEDURE

Th1 (type 1 T helper cells)/Tc1 (T cytotoxic cells, type 1) Rapa cell infusion will be evaluated after administration of a 7-day or 14-day course of immune depleting chemotherapy (pentostatin plus cyclophosphamide regimen).

Cohort A - Prevention of Relapse; Cohort B - Relapsed Multiple Myeloma

Rapamycin-Generated Autologous Th1/Tc1 Cells (modified primary human T cells) BIOLOGICAL

Six Th1/Tc1 Rapa cell doses will be tested in cohorts of 1-6 subjects each: ranging from 10e(5) to 15 x 10e(6) cells/kg of body weight.

Cohort A - Prevention of Relapse

Th1/Tc1 Rapa Cell Therapy BIOLOGICAL

Th1/Tc1Rapa: 5 x 10e(6) cells/kg

Cohort A - Prevention of Relapse; Cohort B - Relapsed Multiple Myeloma

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MULTIPLE MYELOMA CRITERIA:
• Criteria for Cohort A (recently diagnosed subjects; to receive autologous hematopoietic cell transplantation (AHCT)):
• Must have presence of clonal plasma cells in the bone marrow greater or equal to 10% or biopsy proven plasmacytoma
• Must have either:
• presence of an M-component (Immunoglobulin G (IgG) or Immunoglobulin G (IgA)) in serum greater or equal to 1g/dl or in urine greater or equal to 200 mg/24 h; or
• presence of an abnormal serum free light chain (FLC) ratio on the serum FLC assay.
• Criteria for Cohort B (multiply relapsed multiple myeloma):
• Must have measurable multiple myeloma (MM), as defined by: serum M-protein greater than or equal to 1 g/dL, urine M-protein greater than or equal to 200 mg/24 hours, involved serum free light chain (FLC) level greater than or equal to 10 mg/dL, biopsy proven plasmacytoma, or more than 30% bone marrow plasma cells.
• Must have received at least 2 different treatment regimens for MM.
• Other eligibility criteria (applies to both Cohort A and Cohort B, unless specified):

You may not qualify if:

• For Cohort A only, high-dose chemotherapy and AHCT must be planned; with amendment K, post-transplant maintenance therapy will not be permitted.
• Karnofsky performance status (KPS) of 70% or greater. Lower KPS down to 50% may be acceptable if the restriction of activity is solely due to intractable pain from myeloma lesions.
• Ejection fraction (EF) by multi-gated acquisition scan (MUGA) or two-dimensional (2-D) echocardiogram within institution normal limits. In case of low EF, the subject may remain eligible after a stress echocardiogram is performed if the EF is more than 35% and if the increase in EF with stress is estimated at 10% or more.
• Serum creatinine less than or equal to 2.5 mg/dl,
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 times the upper limit of normal.
• Bilirubin less than or equal to1.5 (except if due to Gilbert's disease).
• Corrected carbon monoxide diffusing capacity (DLCO) greater than or equal to 50% on Pulmonary Function Tests
• No history of abnormal bleeding tendency or predisposition to repeated infections.
• Patients must be able to give informed consent
• Prior allogeneic stem cell transplantation
• Hypertension not adequately controlled by 3 or less medications.
• History of cerebro-vascular accident within 6 months of enrollment.
• History of documented pulmonary embolus within 6 months of enrollment.
• Clinically significant cardiac pathology: myocardial infarction within 6 months prior to enrollment, Class III or IV heart failure according to New York Heart Association (NYHA), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Hackensack Meridian Health: collaborator
• Georgetown University: collaborator

Study Sites (2)

National Institutes of Health (NIH) Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (3)

• Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.

  PMID: 18287387 BACKGROUND

• Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990 Feb;33(2):86-9. doi: 10.1002/ajh.2830330203.

  PMID: 2301376 BACKGROUND

• Tosi P, Zamagni E, Cellini C, Plasmati R, Cangini D, Tacchetti P, Perrone G, Pastorelli F, Tura S, Baccarani M, Cavo M. Neurological toxicity of long-term (>1 yr) thalidomide therapy in patients with multiple myeloma. Eur J Haematol. 2005 Mar;74(3):212-6. doi: 10.1111/j.1600-0609.2004.00382.x.

  PMID: 15693790 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Immunotherapy, Adoptive

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

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Limitations and Caveats

3/34 pts signed consent but never received therapy due to progressive malignancy that precluded their ability to receive the experimental therapy. These participants were not assigned to a cohort.

Results Point of Contact

• Title: Dr. Steven Pavletic
• Organization: National Cancer Institute

steven_pavletic@nih.gov

301-402-4899

Study Officials

• Steven Z Pavletic, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 10, 2010
• First Posted: November 11, 2010
• Study Start: November 10, 2010
• Primary Completion: August 16, 2017
• Study Completion: August 16, 2017
• Last Updated: December 10, 2019
• Results First Posted: October 16, 2018

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)