A Multi-Institutional Phase II Feasibility Study of Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Malignant Neuro-Epithelial and Other Solid Tumors
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 30 |
| Updated: | 4/21/2016 |
| Start Date: | September 2015 |
| End Date: | July 2019 |
| Contact: | Kris M Mahadeo, MD, MPH |
| Email: | kmahadeo@montefiore.org |
| Phone: | 718-741-2342 |
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.
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.
This is a multi-institutional Phase II feasibility 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 phase II 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.
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 phase II 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.
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
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