ASCIST: Donor Natural Killer Cell Infusion after Autologous CD133+ Selected Stem Cell Transplant in Treating Younger Patients with High-Risk Solid Tumors or Lymphomas

A Phase I Study of Immunotherapy Including Haploidentical NK Cell Infusion Following CD133+Positively-Selected Autologous Hematopoietic Stem Cells In Children With High-Risk Solid Tumors or Lymphomas

Categories:

Bone Marrow Transplant

Solid Tumor

Phase I/II

Diseases Treated:

High-risk solid tumors and lymphomas

Eligibility Overview:

  • Has a type of high-risk cancer including
    • Neuroblastoma
    • Solid tumors
    • Lymphomas
  • 21 years of age or younger
  • Has not received a prior hematopoietic (blood cells from bone marrow) stem cell transplant within the previous three months
  1. Brief Summary

    This is a pilot clinical trial investigating the addition of haploidentical natural killer (NK) cell infusion to autologous stem cell transplantation. This intervention will be evaluated in children with high-risk solid tumors for whom autologous transplantation is indicated. The effect on normal hematopoietic cell recovery will be evaluated and survival of children treated with this approach will be determined.

    Primary Objective

    To evaluate day +35 ANC engraftment in autologous stem cell transplantation for high risk pediatric malignancies after stem cell selection and immunotherapy.

    Trial Outline

    NK cells from a haploidentical family member will be given after high-dose chemotherapy and positively selected autologous stem cells. In patients with neuroblastoma, the anti-GD2 antibody hu14.18K322A will also be given.

    Study Arms

    Experimental: Group A: Neuroblastoma

    All participants first receive standard of care high-dose chemotherapy specific to their tumor type.

    Interventions

    • Drugs: Busulfan, melphalan
    • Devices: CD133+ selected autologous stem cell infusion, haploidentical natural killer cell infusion
    • Biologicals: hu14.18K322A, IL-2, G-CSF, GM-CSF

    Experimental: Group B: Lymphoma

    All participants first receive standard of care high-dose chemotherapy specific to their tumor type.

    Interventions:

    • Drugs: Bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan
    • Devices: CD133+ selected autologous stem cell infusion, haploidentical natural killer cell infusion
    • Biologicals: IL-2, G-CSF, GM-CSF

    Experimental: Group C: High-Risk Tumors

    All participants first receive standard of care high-dose chemotherapy specific to their tumor type.

    Interventions:

    • Drugs: Melphalan, etoposide (or etoposide phosphate), carboplatin
    • Devices: CD133+ selected autologous stem cell infusion, haploidentical natural killer cell infusion
    • Biologicals: IL-2, G-CSF, GM-CSF

    Eligibility Criteria

    The transplant recipient will be evaluated for eligibility at 2 time points during study participation. The first phase will be when the autologous stem cell product is collected. The recipient will later need to meet specific eligibility criterion at the time of the autologous stem cell infusion. The 2 phases and the respective inclusion criteria are described below.

    Inclusion criteria for autologous stem cell collection (Phase 1 - transplant recipient):

    • Less than or equal to 21 years of age
    • Malignancy at high risk of treatment failure for which autologous hematopoietic stem cell transplantation is considered within standard practice
      • Group A: High-risk neuroblastoma
      • Group B: Recurrent or refractory Hodgkin lymphoma; recurrent or refractory non-Hodgkin lymphoma
      • Group C: High-risk, recurrent or metastatic sarcoma; recurrent or advanced stage Wilms tumor; desmoplastic small round cell tumor; metastatic or recurrent retinoblastoma, high-risk germ cell tumors, and high-risk brain tumors
    • Sarcoma or Wilms tumor diagnosis (Group C) will require evaluation by physician in the St. Jude Solid Tumor Division, other than the referring physician, attesting that autologous SCT provides the prospect of direct benefit for the participant
    • Has a potentially suitable human leukocyte antigen (HLA) haploidentical donor available.
    • Does not have any active or prior malignant or pre-malignant condition of the bone marrow, excluding metastasis of the primary malignancy.
    • Has no known allergy to murine products or positive human anti-mouse antibody (HAMA)
    • Not pregnant or breastfeeding

    Inclusion criteria to proceed with autologous stem cell transplantation (Phase 2 - transplant recipient):

    • Has a confirmed suitable HLA haploidentical donor available
    • Previously collected autologous stem cell product met the minimum collection target and minimum infusion target (as described in the protocol)
    • At least 2 weeks since receipt of any biological therapy, chemotherapy, and/or radiation therapy
    • Has recovered from all acute NCI Common Toxicity Criteria grade II-IV non-hematologic toxicities from prior therapy per the judgment of the PI
    • Shortening fraction ≥25%
    • Creatinine clearance or glomerular filtration rate ≥50 mL/min/1.73 m2
    • Pulse oximetry ≥92% on room air
    • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 times the upper limit of the institution-established normal range
    • Direct bilirubin ≤3.0 mg/dL
    • Karnofsky or Lansky performance score of ≥50
    • Has not received a prior hematopoietic stem cell transplant within 3 months
    • Has no known allergy to murine products or positive HAMA
    • Is not pregnant or breastfeeding

    Study Design

    • Allocation: Non-randomized
    • Endpoint Classification: Safety/Efficacy Study
    • Intervention Model: Parallel Assignment
    • Masking: Open Label
    • Primary Purpose: Treatment

  2. About this clinical trial

    St. Jude is offering this clinical trial to see if remission rates in patients with high-risk solid tumors and lymphomas can be improved. Remission means no signs or symptoms of disease.

    Standard treatment for these high-risk cancers usually includes treatment with an autologous stem cell transplant. Some patients with high-risk solid tumors and lymphomas have attained remission by using stem cell transplantation.

    In stem cell transplantation, healthy stem cells (the blood-forming cells in the bone marrow) are used to replace the cancer cells that have been killed by chemo and/or radiation therapy. Stem cells can be collected from the patient (autologous) or from a donor (allogeneic).

    In ASCIST, St. Jude researchers will be using a different stem cell selection process and also adding a type white blood cell, called natural killer (NK) cells, provided by a family member donor.

    Purpose of this clinical trial

    The main purpose of ASCIST is to find out how well a combination of transplanted stem cells and NK cells will work to prevent your child’s cancer from returning.

    Treatment

    There are three parts to this research study:

    • Screening – Tests and procedures will be done to find out if this study is a good option for you/your child.
    • Treatment – Treatment will include chemotherapy followed by stem cell- and NK cell-transplantation. Participants with neuroblastoma will also be given the monoclonal antibody hu14.18K322A, a man-made version of an immune system protein that finds and attaches to the surface of most neuroblastoma cells. It is hoped that the immune system will attack and kill the cancer cells without harming nearby healthy cells.  
    • Follow-up – After treatment ends, your child will have routine follow-up examinations and medical tests. St. Jude researchers will continue to collect medical information about how your child is doing after he or she completes treatment.

    Eligibility overview

    • Has a type of high-risk cancer including
      • Neuroblastoma
      • Solid tumors
      • Lymphomas
    • 21 years of age or younger
    • Has not received a prior hematopoietic (blood cells from bone marrow) stem cell transplant within the previous three months
  3. ASCIST Quick View
    Sponsor St. Jude Children's Research Hospital
    Clinicaltrials.gov identifier NCT02130869
    Trial start date September 2014
    Estimated enrollment 36
    Study type Interventional
    Study phase Phase 1
    Conditions
    • High-risk neuroblastoma
    • High-risk solid tumors
    • High-risk lymphomas
    Ages
    Up to 21 years
    Principal investigator Brandon Triplett, MD
    Study site St. Jude Children’s Research Hospital
    For a consultation or to discuss ASCIST St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Brandon Triplett, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.