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Neuroepithelial TumorEarly Phase 1NCT02653196

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

A Early Phase 1 study testing Allogeneic hematopoietic stem cell transplant following thiotepa-based marrow ablative chemotherapy, Keratinocyte Growth Factor and Alemtuzumab in people with Neuroepithelial Tumor and Solid Tumor, run by Montefiore Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 60 years
What is being tested?
Allogeneic hematopoietic stem cell transplant following thiotepa-based marrow ablative chemotherapy, Keratinocyte Growth Factor and Alemtuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
Sep 2015to Aug 2017
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Children's Hospital at Montefiore

    The Bronx, New York, 10467

Other trials in United States

About this study

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.

Read the 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.

Being tested
Allogeneic hematopoietic stem cell transplant following thiotepa-based marrow ablative chemotherapy, Keratinocyte Growth Factor, Alemtuzumab, Thiotepa, Etoposide
Medical subject headings
Neoplasms, Neuroepithelial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic hematopoietic stem cell transplant following thiotepa-based marrow ablative chemotherapyProcedure or surgery

    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.

  • Keratinocyte Growth FactorDrug

    Also called KGF, Kepivance, Palifermin

    KGF 60 mcg/kg IV: 6 doses

  • AlemtuzumabDrug

    Also called Campath, Campath 1H

    Alemtuzumab 12 mg/m2 IV: 2 doses (not given if matched related donor is 10/10 HLA matched sibling donor)

  • ThiotepaDrug

    Thiotepa 300 mg/m2 IV: 3 doses

  • EtoposideDrug

    Also called VP-16

    Etoposide 100 mg/m2 IV: 3 doses

  • FludarabineDrug

    Also called FLUDARA

    Fludarabine 30 mg/m2 IV: 3 doses

  • MelphalanDrug

    Melphalan 70 mg/m2 IV: Day 2 doses

  • TacrolimusDrug

    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

  • Cyclosporine ADrug

    Also called Cyclosporine, CYA, CSA, Sandimmune

    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

  • Mycophenolate mofetilDrug

    Also called MMF, Cellcept, Myfortic

    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

Study groups in NCT02653196
Study groupRoleWhat they receive
Allogeneic Hematopoietic Stem Cell TransplantExperimentalMatched 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
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival

    Measured: Six months post-transplant

Secondary outcomes (5)

  1. Overall Survival

    Measured: One year post-transplant

  2. Transplant Related Mortality

    Measured: Day +100 post-transplant

  3. Engraftment

    Measured: Within 100 days post-transplant

  4. Regimen Related Toxicity

    Frequency and severity of acute and chronic graft-versus-host disease

    Measured: Within one year post-transplant

  5. Time to Immune Reconstitution

    Measured: Within one year post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2016 (estimated)
  2. Study startSep 2015
  3. Primary completionAug 2017
  4. Study completionAug 2017

Why it stopped: The Principal Investigator left the institution.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02653196
Sponsor's protocol ID
2014-3856
Status last verified
Jun 2017
First submitted
7 Jan 2016
Last updated
17 Aug 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Smith MA, Seibel NL, Altekruse SF, Ries LA, Melbert DL, O'Leary M, Smith FO, Reaman GH. Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol. 2010 May 20;28(15):2625-34. doi: 10.1200/JCO.2009.27.0421. Epub 2010 Apr 19.

    PubMed 20404250

  • Chow KH, Gottschalk S. Cellular immunotherapy for high-grade glioma. Immunotherapy. 2011 Mar;3(3):423-34. doi: 10.2217/imt.10.110.

    PubMed 21395383

  • Daniels BP, Cruz-Orengo L, Pasieka TJ, Couraud PO, Romero IA, Weksler B, Cooper JA, Doering TL, Klein RS. Immortalized human cerebral microvascular endothelial cells maintain the properties of primary cells in an in vitro model of immune migration across the blood brain barrier. J Neurosci Methods. 2013 Jan 15;212(1):173-9. doi: 10.1016/j.jneumeth.2012.10.001. Epub 2012 Oct 13.

    PubMed 23068604

  • Mitchell DA, Fecci PE, Sampson JH. Immunotherapy of malignant brain tumors. Immunol Rev. 2008 Apr;222:70-100. doi: 10.1111/j.1600-065X.2008.00603.x.

    PubMed 18363995

  • Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1;24(25):4202-8. doi: 10.1200/JCO.2006.06.4980.

    PubMed 16943538

  • Finlay JL, Goldman S, Wong MC, Cairo M, Garvin J, August C, Cohen BH, Stanley P, Zimmerman RA, Bostrom B, Geyer JR, Harris RE, Sanders J, Yates AJ, Boyett JM, Packer RJ. Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children's Cancer Group. J Clin Oncol. 1996 Sep;14(9):2495-503. doi: 10.1200/JCO.1996.14.9.2495.

    PubMed 8823328

  • Sung KW, Yoo KH, Cho EJ, Koo HH, Lim DH, Shin HJ, Ahn SD, Ra YS, Choi ES, Ghim TT. High-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk or relapsed medulloblastoma or supratentorial primitive neuroectodermal tumor. Pediatr Blood Cancer. 2007 Apr;48(4):408-15. doi: 10.1002/pbc.21064.

    PubMed 17066462

  • Ris MD, Packer R, Goldwein J, Jones-Wallace D, Boyett JM. Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children's Cancer Group study. J Clin Oncol. 2001 Aug 1;19(15):3470-6. doi: 10.1200/JCO.2001.19.15.3470.

    PubMed 11481352

  • Henon PR, Butturini A, Gale RP. Blood-derived haematopoietic cell transplants: blood to blood? Lancet. 1991 Apr 20;337(8747):961-3. doi: 10.1016/0140-6736(91)91583-g. No abstract available.

    PubMed 1678042

  • Mason WP, Grovas A, Halpern S, Dunkel IJ, Garvin J, Heller G, Rosenblum M, Gardner S, Lyden D, Sands S, Puccetti D, Lindsley K, Merchant TE, O'Malley B, Bayer L, Petriccione MM, Allen J, Finlay JL. Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors. J Clin Oncol. 1998 Jan;16(1):210-21. doi: 10.1200/JCO.1998.16.1.210.

    PubMed 9440745

  • Shih CS, Hale GA, Gronewold L, Tong X, Laningham FH, Gilger EA, Srivastava DK, Kun LE, Gajjar A, Fouladi M. High-dose chemotherapy with autologous stem cell rescue for children with recurrent malignant brain tumors. Cancer. 2008 Mar 15;112(6):1345-53. doi: 10.1002/cncr.23305.

    PubMed 18224664

  • Gururangan S, Krauser J, Watral MA, Driscoll T, Larrier N, Reardon DA, Rich JN, Quinn JA, Vredenburgh JJ, Desjardins A, McLendon RE, Fuchs H, Kurtzberg J, Friedman HS. Efficacy of high-dose chemotherapy or standard salvage therapy in patients with recurrent medulloblastoma. Neuro Oncol. 2008 Oct;10(5):745-51. doi: 10.1215/15228517-2008-044. Epub 2008 Aug 28.

    PubMed 18755919

  • Butturini AM, Jacob M, Aguajo J, Vander-Walde NA, Villablanca J, Jubran R, Erdreich-Epstein A, Marachelian A, Dhall G, Finlay JL. High-dose chemotherapy and autologous hematopoietic progenitor cell rescue in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors: the impact of prior radiotherapy on outcome. Cancer. 2009 Jul 1;115(13):2956-63. doi: 10.1002/cncr.24341.

    PubMed 19402050

  • Lundberg JH, Weissman DE, Beatty PA, Ash RC. Treatment of recurrent metastatic medulloblastoma with intensive chemotherapy and allogeneic bone marrow transplantation. J Neurooncol. 1992 Jun;13(2):151-5. doi: 10.1007/BF00172764.

    PubMed 1432032

  • Secondino S, Pedrazzoli P, Schiavetto I, Basilico V, Bramerio E, Massimino M, Gambacorta M, Siena S. Antitumor effect of allogeneic hematopoietic SCT in metastatic medulloblastoma. Bone Marrow Transplant. 2008 Jul;42(2):131-3. doi: 10.1038/bmt.2008.86. Epub 2008 Mar 31. No abstract available.

    PubMed 18372908

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Allogeneic hematopoietic stem cell transplant following thiotepa-based marrow ablative chemotherapy, Keratinocyte Growth Factor and Alemtuzumab in people with Neuroepithelial Tumor and Solid Tumor, run by Montefiore Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The Principal Investigator left the institution.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (time frame: Six months post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02653196, which also lists 49 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2017.

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