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A Multi-Institutional Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Malignant Neuro-Epithelial and Other Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02653196
Recruitment Status : Terminated (The Principal Investigator left the institution.)
First Posted : January 12, 2016
Last Update Posted : August 17, 2017
Sponsor:
Collaborators:
Children's Hospital Los Angeles
Nationwide Children's Hospital
Information provided by (Responsible Party):
Kris M. Mahadeo, Montefiore Medical Center

Brief Summary:
There is currently no standard treatment for patients with neuro-epithelial (brain) or other solid tumors in another part of the body who do not have adequate suitable autologous hematopoietic progenitor cells available and/or whose disease has relapsed after standard treatment. Allogeneic Hematopoietic Progenitor Cell Transplant may be a consideration for treatment of patients with recurrent chemo-responsive malignant (high grade) neuro-epithelial and other solid tumors or those who do not have suitable autologous hematopoietic progenitor cell availability. The procedure in which your own blood stem cells are transplanted to you is called an autologous (from your own) progenitor cell transplant and when cells from a matched donor are transfused is called an allogeneic progenitor cell transplant. The study is being conducted to evaluate the safety and effectiveness of a combination of drugs followed by an allogeneic hematopoietic progenitor cell transplant (HPCT). This treatment regimen is experimental in that although the individual drugs are commonly used to treat your disease, the specific combination used in this protocol followed by the transplant is experimental.

Condition or disease Intervention/treatment Phase
Neuroepithelial Tumor Solid Tumor Allogeneic Hematopoietic Stem Cell Transplantation Procedure: Allogeneic hematopoietic stem cell transplant following thiotepa-based marrow ablative chemotherapy Drug: Keratinocyte Growth Factor Drug: Alemtuzumab Drug: Thiotepa Drug: Etoposide Drug: Fludarabine Drug: Melphalan Drug: Tacrolimus Drug: Cyclosporine A Drug: Mycophenolate mofetil Early Phase 1

Detailed Description:

This is a multi-institutional Pilot clinical trial of hematopoietic stem cell transplantation (HSCT) for (i) patients with recurrent chemo-responsive malignant (high-grade) neuro-epithelial and other solid tumors which are recurrent following HSCT or (ii) for said patients without autologous hematopoietic progenitor cell availability. The stem cells will be derived from a 1) matched related donor or 2) matched unrelated donor (MUD).

This is a pilot study of a novel HSCT protocol for patients with high-grade and/or recurrent neuro-epithelial and other solid tumors. To determine the feasibility of allogeneic HSCT following thiotepa-based marrow ablative chemotherapy (MAC) for children with high-grade and/or recurrent neuro-epithelial and other solid tumors. The primary end-point for this study is to determine progression-free survival (PFS) at six months post-HSCT. Secondary end-points include: (a) overall survival (OS) at one year (b) transplant related mortality (TRM) at Day +100 (c) engraftment (d) regimen related toxicity: the frequency and severity of acute and chronic graft-versus-host disease (GVHD), sinusoidal obstructive syndrome and infections will be assessed (e) time to immune reconstitution following HSCT. Exploratory Aims include: 1) To assess the feasibility of the Taqman® Low Density Arrays (TLDA) assay as a technology for MRD detection among a subset of patients with high-grade and/or recurrent neuro-epithelial and other solid tumors. Minimal residual disease (MRD) (when applicable) in bone marrow pre- and post-HSCT, will be assessed using TLDA. Currently, for solid malignancies there is no routinely established method to detect minimal residual disease, the first indicator of therapy failure and/or recurrence of disease. 2) In an effort to minimize morbidity related to graft-versus-host disease, alemtuzumab forms an important component of the proposed MAC regimen for recipients of unrelated or related mismatched allogeneic grafts. As an exploratory aim, an alemtuzumab assay will be performed at specified intervals to explore time to drug clearance. This may provide important information regarding lymphodepletion for future trials regarding immunotherapy administered during recovery from HSCT therapy.

The main advantages of the proposed approach will: 1) Overcome the challenges in bone morrow/peripheral blood stem cell (PBSC) collection in patients heavily pre-treated and/or bone/bone marrow infiltration with tumor. 2) Eliminate the risk of graft contamination with tumor cells, and 3) Graft-versus-tumor effect (GVT) to eliminate residual disease after conditioning chemotherapy. The use of allografting with the proposed regimen combines the benefits of high dose chemotherapy and an immune approach to disease therapy.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Institutional Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Malignant Neuro-Epithelial and Other Solid Tumors
Study Start Date : September 2015
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Allogeneic Hematopoietic Stem Cell Transplant

Matched Unrelated Donor HSCT (minimum 9/10 human leukocyte antigen [HLA] match) OR Matched Related Donor HSCT (10/10 HLA match). Conditioning regimen begins 12 days prior to stem cell infusion and includes the following drugs:

Keratinocyte Growth Factor Alemtuzumab Thiotepa Etoposide Melphalan Fludarabine Tacrolimus (Cyclosporine A may be substituted for Tacrolimus) Mycophenolate mofetil

Procedure: Allogeneic hematopoietic stem cell transplant following thiotepa-based marrow ablative chemotherapy
Allogeneic hematopoietic stem cell transplant (HSCT) following thiotepa-based marrow ablative chemotherapy (MAC) for children with high-grade and/or recurrent neuro-epithelial and other solid tumors.

Drug: Keratinocyte Growth Factor
KGF 60 mcg/kg IV: 6 doses
Other Names:
  • KGF
  • Kepivance
  • Palifermin

Drug: Alemtuzumab
Alemtuzumab 12 mg/m2 IV: 2 doses (not given if matched related donor is 10/10 HLA matched sibling donor)
Other Names:
  • Campath
  • Campath 1H

Drug: Thiotepa
Thiotepa 300 mg/m2 IV: 3 doses

Drug: Etoposide
Etoposide 100 mg/m2 IV: 3 doses
Other Name: VP-16

Drug: Fludarabine
Fludarabine 30 mg/m2 IV: 3 doses
Other Name: FLUDARA

Drug: Melphalan
Melphalan 70 mg/m2 IV: Day 2 doses

Drug: Tacrolimus
Tacrolimus 0.05 mg/kg/day IV (Cyclosporine may be substituted for Tacrolimus): Start Day -2, begin taper on Day +100, discontinue on Day +180

Drug: Cyclosporine A
Cyclosporine A dosed as follows: Age ≤ 6 years: 6 mg/kg/day IV in divided doses (e.g. 2 mg/kg every 8 hours) OR Age > 6 years: 3 mg/kg/day IV in divided doses (1.5 mg/kg every 12 hours): Start Day -2, begin taper on Day +100, discontinue on Day +180
Other Names:
  • Cyclosporine
  • CYA
  • CSA
  • Sandimmune
  • Neoral
  • Gengraf

Drug: Mycophenolate mofetil
Mycophenolate mofetil 15 mg/kg every 8 hours oral or IV: Start Day 0 (4-6 hours post stem cell infusion) to Day +40, then taper weekly until discontinuation on Day +90
Other Names:
  • MMF
  • Cellcept
  • Myfortic




Primary Outcome Measures :
  1. Progression-Free Survival [ Time Frame: Six months post-transplant ]

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: One year post-transplant ]
  2. Transplant Related Mortality [ Time Frame: Day +100 post-transplant ]
  3. Engraftment [ Time Frame: Within 100 days post-transplant ]
  4. Regimen Related Toxicity [ Time Frame: Within one year post-transplant ]
    Frequency and severity of acute and chronic graft-versus-host disease

  5. Time to Immune Reconstitution [ Time Frame: Within one year post-transplant ]

Other Outcome Measures:
  1. Feasibility of Taqman® Low Density Arrays (TLDA) [ Time Frame: Prior to stem cell infusion to one year post-transplant, at specified intervals. ]
    Use of TLDA assay as a technology for MRD detection among a subset of patients with high-grade and/or recurrent neuro-epithelial and other solid tumors.

  2. Alemtuzumab Assay [ Time Frame: Ten days prior to stem cell infusion to 28 days post-transplant, at specified intervals ]
    The Alemtuzumab assay will explore time to drug clearance. This may provide important information regarding lymphodepletion for future trials regarding immunotherapy administered during recovery from HSCT therapy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Malignant (high-grade) neuro-epithelial and other solid tumors
  • Patients have to be in at least, a chemo-responsive disease status defined as; any disease regression to chemotherapy when compared to its pre-treatment evaluation
  • Patients with recurrent (or refractory) chemo-responsive disease or without suitable autologous hematopoietic progenitor cell availability
  • Creatinine clearance or glomerular filtration rate (GFR) ≥50 ml/min/1.73m2, and not requiring dialysis
  • Diffusing capacity of lung for carbon monoxide, or DLCO, (corrected for hemoglobin) ≥ 50% predicted. If unable to perform pulmonary function tests, then oxygen (O2) saturation ≥ 92% in room air
  • Bilirubin ≤3x upper limit of normal (ULN) and alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 5x for age (with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome)

Exclusion Criteria:

  • Lack of histocompatible suitable related or unrelated donor/ graft source
  • End-organ failure that precludes the ability to tolerate the transplant procedure, including conditioning
  • Renal failure requiring dialysis
  • Congenital heart disease resulting in congestive heart failure
  • Ventilatory failure
  • HIV infection
  • Uncontrolled bacterial, viral, or fungal infections (currently taking medication yet clinical symptoms progress); stable, controlled disease with treatment is not an exclusion criteria
  • Female of reproductive potential who is pregnant, planning to become pregnant during the study, or is nursing a child

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02653196


Locations
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United States, New York
The Children's Hospital at Montefiore
The Bronx, New York, United States, 10467
Sponsors and Collaborators
Montefiore Medical Center
Children's Hospital Los Angeles
Nationwide Children's Hospital
Investigators
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Principal Investigator: Kris M Mahadeo, MD,MPH The Children's Hospital at Montefiore
Publications:

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Responsible Party: Kris M. Mahadeo, Assistant Professor, Montefiore Medical Center
ClinicalTrials.gov Identifier: NCT02653196    
Other Study ID Numbers: 2014-3856
First Posted: January 12, 2016    Key Record Dates
Last Update Posted: August 17, 2017
Last Verified: June 2017
Additional relevant MeSH terms:
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Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclosporine
Mycophenolic Acid
Fludarabine
Etoposide
Melphalan
Alemtuzumab
Thiotepa
Tacrolimus
Cyclosporins
Mitogens
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Calcineurin Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents