Clinical trial NCT04530487: Donor Stem Cell Transplant After Chemotherapy for the Treatment of Recurrent or Refractory High-Risk Solid Tumors in Pediatric and Adolescent-Young Adults
Official title: A Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric and Adolescent-Young Adults Patients With High Risk Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Desmoplastic Small Round Cell Tumor
Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recurrent Desmoplastic Small Round Cell Tumor
Recurrent Malignant Peripheral Nerve Sheath Tumor
Recurrent Malignant Solid Neoplasm
Recurrent Neuroblastoma
Recurrent Rhabdomyosarcoma
Refractory Desmoplastic Small Round Cell Tumor
Refractory Malignant Peripheral Nerve Sheath Tumor
Refractory Malignant Solid Neoplasm
Refractory Neuroblastoma
Refractory Rhabdomyosarcoma
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2020-08-28
Enrollment: 1
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial investigates side effects and how well donor stem cell transplant after chemotherapy works in treating pediatric and adolescent-young adults with high-risk solid tumor that has come back (recurrent) or does not respond to treatment (refractory). Chemotherapy drugs, such as fludarabine, thiotepa, etoposide, melphalan, and rabbit anti-thymocyte globulin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a donor stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells.

Detailed description: PRIMARY OBJECTIVE:

I. To assess tolerability of allogeneic hematopoietic stem cell transplantation (HCT) for patients with chemo-responsive recurrent/refractory solid tumors as defined by transplant-related mortality (TRM) at day 30 and the rate of grade III or higher organ toxicity (Bearman Regimen-Related Toxicities Scale) attributable to conditioning occurring within 30 days.

SECONDARY OBJECTIVES:

I. Assess median time to platelet and neutrophil engraftment. II. Assess incidence of acute graft-versus-host disease (aGVHD) by day 100. III. Assess incidence of chronic GVHD (cGVHD) at day 100 and one year. IV. Assess rate of grade II organ toxicity through day 100. V. Assess rate of graft failure (primary and secondary) through day 100. VI. Assess rate of infectious complications through day 100. VII. Assess progression free survival (PFS) at day 100,180 and 365. VIII. Assess cumulative incidence of relapse, overall survival (OS) at 100 days and 1 year.

OUTLINE:

CONDITIONING REGIMEN: Patients receive thiotepa intravenously (IV) over 2-4 hours and etoposide IV over 60 minutes on days -8 to -6, melphalan IV over 20 minutes on days -5 and -4, and fludarabine phosphate IV over 1 hour on days -5 to -3 in the absence of disease progression or unacceptable toxicity. Patients receiving umbilical cord transplant also receive rabbit anti-thymocyte globulin IV on days -4 and -3.

TRANSPLANT: Patients undergo HSCT on day 0.

GVHD PROPHYLAXIS: Beginning day -2, patients receive tacrolimus or cyclosporine IV continuously until able to receive orally (PO). Patients continue tacrolimus or cyclosporine PO to day 60 and tapered to day 100. Patients also receive mycophenolate mofetil PO or IV every 8 hours until day 40 and tapered to day 90.

After completion of HSCT, patients are followed up for up to 1 year.

Eligibility criteria: Inclusion Criteria:

* Pathological criteria, including malignant recurrent/refractory solid tumors. This would include:

  * Ewing's/peripheral primitive neuroectodermal tumor (PNET)
  * Malignant peripheral nerve sheath tumor, neurofibrosarcoma
  * Rhabdomyosarcoma
  * Neuroblastoma (patients who are ineligible for tandem autologous transplant or who are at least 3 months post autologous HCT)
  * Desmoplastic small round cell tumor (DSRCT)- both new diagnoses as well as recurrent/refractory disease
* Patients must have chemo-responsive disease, defined as; 30% or greater decrease in the tumor target lesions when compared to its pre-treatment evaluation. Patients with complete response will be eligible to participate
* Available suitable HCT donor
* Creatinine clearance or glomerular filtration rate (GFR) \>= 50 ml/min/1.73m\^2, and not requiring dialysis
* Diffusing capacity of lung for carbon monoxide (DLCO) (corrected for hemoglobin) \>= 50% predicted. If unable to perform pulmonary function tests, then oxygen (O2) saturation \>= 92% in room air
* Bilirubin =\< 3 x upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 5 x for age (with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome)
* DONOR: Matched related donor bone marrow (10 of 10 HLA alleles \[HLA-A, B, C, DR, and DQ\]. Matched related donor peripheral blood stem cell (PBSC) is allowed only if collection of bone marrow (BM) is not available or refused by parents/donor
* DONOR: Matched allogeneic umbilical cord blood (UCB): related

  * High-resolution matching at A,B, DRB1 (minimum 4/6)
  * KIR major histocompatibility complex (MHC) class 1 preferential mismatch (minimum 4/6)
* DONOR: Matched allogeneic umbilical cord blood: unrelated

  * High-resolution matching at A,B, DRB1 (minimum 4/6) •\*KIR MHC class 1 preferential mismatch (minimum 4/6)

Exclusion Criteria:

* Lack of histocompatible suitable related donor/ graft source
* End-organ failure that precludes the ability to tolerate the transplant procedure, including conditioning regimen
* Renal failure requiring dialysis
* Congenital heart disease resulting in congestive heart failure
* Ventilatory failure: requires invasive mechanical ventilation
* Human immunodeficiency virus (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
* A female of reproductive potential who is pregnant, planning to become pregnant during the study, or is nursing a child
* Any patient who does not fulfill the inclusion criteria listed above

Primary outcomes:
measure: Transplant-related mortality (TRM)
timeFrame: At 30 days
measure: Rate of grade III or higher organ toxicity attributable to conditioning
timeFrame: Up to 30 days
Secondary outcomes:
measure: Time to platelet and neutrophil engraftment
timeFrame: Up to 1 year post transplant
measure: Incidence of acute graft versus host disease (aGVHD)
timeFrame: At 100 days post transplant
measure: Incidence of chronic GVHD
timeFrame: At 100 days post transplant
measure: Incidence of chronic GVHD
timeFrame: At 1 year post transplant
measure: Rate of grade II organ toxicity
timeFrame: Up to 100 days post transplant
measure: Rate of graft failure (primary and secondary)
timeFrame: Up to 100 days post transplant
measure: Rate of infectious complications
timeFrame: Up to 100 days post transplant
measure: Progression-free survival (PFS)
timeFrame: At 180 days post transplant
measure: PFS
timeFrame: At 100 days post transplant
measure: PFS
timeFrame: At 1 year post transplant
measure: Incidence of relapse
timeFrame: At 100 days post transplant
measure: Incidence of relapse
timeFrame: At 1 year post transplant
measure: Overall survival (OS)
timeFrame: At 100 days post transplant
measure: OS
timeFrame: At 1 year post transplant
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jeremy S Connors, MD
role: PRINCIPAL_INVESTIGATOR
References: