Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes in the Autologous Transplant Setting in Multiple Myeloma
- Evaluate the safety and response rate of activated marrow infiltrating lymphocytes
(aMILs) in patients undergoing autologous peripheral blood stem cell transplantation
for newly diagnosed, stage II-III multiple myeloma.
- Determine the overall in vitro fold-expansion and assess pre- and post-expansion for
myeloma T-cell specificity in assessing the feasibility of generating aMILs from
- Assess the toxicity of aMILs.
- Evaluate the effect of aMILs on hematopoietic engraftment, including neutrophil
engraftment, platelet engraftment, and primary graft failure (if failure occurs).
- Evaluate response rates utilizing the Blade criteria, including the complete response
(CR) rate, near complete response (nCR) rate, very good partial response (VGPR) rate,
partial response (PR) rate, minimal response (MR) rate, and overall response rate (CR,
VGPR, PR, MR).
- Evaluate T-cell reconstitution, including absolute lymphocyte counts, CD3+, CD4+, and
CD8+ T-cell counts.
- Evaluate progression-free survival and overall survival.
- Evaluate anti-tumor immune response.
- Determine pneumococcal-specific vaccine responses.
- Determine delayed-type hypersensitivity (DTH) responses.
OUTLINE: Patients undergo collection of marrow infiltrating lymphocytes (MILs)* either at
diagnosis prior to the initiation of induction therapy or upon completion of induction
therapy. The MILs bone marrow product undergo ex vivo activation and expansion of T cells
for 7-8 days to produce activated marrow infiltrating lymphocytes (aMILs). Patients then
undergo stem cell mobilization and leukapheresis to collect the peripheral blood stem cells
12 days after mobilization. Patients receive melphalan IV over 20-30 minutes on days -2 and
-1 and undergo a peripheral blood stem cell transplantation on day 0 as planned. Patients
receive aMILs infusion on day 3. Patients receive pneumococcal polyvalent vaccine on day 21.
NOTE: *Patients who have completed induction therapy receive pneumococcal polyvalent vaccine
approximately 2 weeks prior to MILs collection; patients undergoing MILs collection prior to
starting induction therapy do not receive a pre-transplantation vaccine.
Blood and bone marrow samples are collected periodically for laboratory correlative studies.
After completion of study treatment, patients are followed periodically for up to 1 year.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Ivan Borrello, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|