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

August 14, 2017 updated by: Kris M. Mahadeo, Montefiore Medical Center
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • The Bronx, New York, United States, 10467
        • The Children's Hospital at Montefiore

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • Kepivance
  • KGF
  • 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 Names:
  • VP-16
Drug: Fludarabine
Fludarabine 30 mg/m2 IV: 3 doses
Other Names:
  • 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:
  • Sandimmune
  • Cyclosporine
  • Neoral
  • CSA
  • Gengraf
  • CYA
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:
  • Cellcept
  • Myfortic
  • MMF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-Free Survival
Time Frame: Six months post-transplant
Six months post-transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: One year post-transplant
One year post-transplant
Transplant Related Mortality
Time Frame: Day +100 post-transplant
Day +100 post-transplant
Engraftment
Time Frame: Within 100 days post-transplant
Within 100 days post-transplant
Regimen Related Toxicity
Time Frame: Within one year post-transplant
Frequency and severity of acute and chronic graft-versus-host disease
Within one year post-transplant
Time to Immune Reconstitution
Time Frame: Within one year post-transplant
Within one year post-transplant

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Prior to stem cell infusion to one year post-transplant, at specified intervals.
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.
Ten days prior to stem cell infusion to 28 days post-transplant, at specified intervals

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Montefiore Medical Center

Collaborators

Nationwide Children's Hospital
Children's Hospital Los Angeles

Investigators

  • Principal Investigator: Kris M Mahadeo, MD,MPH, The Children's Hospital at Montefiore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (Actual)

August 1, 2017

Study Completion (Actual)

August 1, 2017

Study Registration Dates

First Submitted

January 7, 2016

First Submitted That Met QC Criteria

January 8, 2016

First Posted (Estimate)

January 12, 2016

Study Record Updates

Last Update Posted (Actual)

August 17, 2017

Last Update Submitted That Met QC Criteria

August 14, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014-3856

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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