- ICH GCP
- US Clinical Trials Registry
- 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
A Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric and Adolescent-Young Adults Patients With High Risk Solid Tumors
Study Overview
Status
Conditions
- Refractory Malignant Solid Neoplasm
- Recurrent Malignant Solid Neoplasm
- Recurrent Neuroblastoma
- Recurrent Rhabdomyosarcoma
- Refractory Neuroblastoma
- Refractory Rhabdomyosarcoma
- Desmoplastic Small Round Cell Tumor
- Recurrent Malignant Peripheral Nerve Sheath Tumor
- Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
- Recurrent Desmoplastic Small Round Cell Tumor
- Refractory Desmoplastic Small Round Cell Tumor
- Refractory Malignant Peripheral Nerve Sheath Tumor
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jeremy S Connors, MD
- Phone Number: (713) 792-6624
- Email: jsconnors@mdanderson.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
-
Contact:
- Jeremy S Connors, MD
- Phone Number: 713-792-6624
- Email: jsconnors@mdanderson.org
-
Principal Investigator:
- Jeremy S Connors, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
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: Treatment (conditioning regimen, HSCT)
CONDITIONING REGIMEN: Patients receive thiotepa IV over 2-4 hours, 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 -3 and -4. TRANSPLANT: Patients undergo HSCT on day 0. GVHD PROPHYLAXIS: Beginning day -2, patients receive tacrolimus or cyclosporine IV continuously until able to receive 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. |
Given IV
Other Names:
Given IV
Other Names:
Given IV and PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Undergo HSCT
Other Names:
Given IV and PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Transplant-related mortality (TRM)
Time Frame: At 30 days
|
The proportion of patients with 30-day TRM will be reported together with the corresponding 95% Bayesian credible interval.
|
At 30 days
|
Rate of grade III or higher organ toxicity attributable to conditioning
Time Frame: Up to 30 days
|
Assessed using the Bearman Regimen-Related Toxicities Scale.
The proportion of patients with 30-day grade III or higher organ toxicity will be reported together with the corresponding 95% Bayesian credible interval.
|
Up to 30 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to platelet and neutrophil engraftment
Time Frame: Up to 1 year post transplant
|
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
|
Up to 1 year post transplant
|
Incidence of acute graft versus host disease (aGVHD)
Time Frame: At 100 days post transplant
|
The 100-day rates of acute with the competing risk of relapse will be estimated using the method of Gooley.
|
At 100 days post transplant
|
Incidence of chronic GVHD
Time Frame: At 100 days post transplant
|
The 100-day rates of chronic GVHD with the competing risk of relapse will be estimated using the method of Gooley
|
At 100 days post transplant
|
Incidence of chronic GVHD
Time Frame: At 1 year post transplant
|
The 1 year rates of chronic GVHD with the competing risk of relapse will be estimated using the method of Gooley.
|
At 1 year post transplant
|
Rate of grade II organ toxicity
Time Frame: Up to 100 days post transplant
|
The 100-day rates of grade II organ toxicity will be reported as counts with percentages.
|
Up to 100 days post transplant
|
Rate of graft failure (primary and secondary)
Time Frame: Up to 100 days post transplant
|
The 100-day rates of primary and secondary graft failure will be reported as counts with percentages.
|
Up to 100 days post transplant
|
Rate of infectious complications
Time Frame: Up to 100 days post transplant
|
The 100-day rates of infectious complications will be reported as counts with percentages.
|
Up to 100 days post transplant
|
Progression-free survival (PFS)
Time Frame: At 180 days post transplant
|
Will be assessed using the method of Kaplan and Meier.
|
At 180 days post transplant
|
PFS
Time Frame: At 100 days post transplant
|
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
|
At 100 days post transplant
|
PFS
Time Frame: At 1 year post transplant
|
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
|
At 1 year post transplant
|
Incidence of relapse
Time Frame: At 100 days post transplant
|
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
|
At 100 days post transplant
|
Incidence of relapse
Time Frame: At 1 year post transplant
|
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
|
At 1 year post transplant
|
Overall survival (OS)
Time Frame: At 100 days post transplant
|
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
|
At 100 days post transplant
|
OS
Time Frame: At 1 year post transplant
|
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
|
At 1 year post transplant
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jeremy S Connors, MD, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Neuromuscular Diseases
- Neoplasms, Neuroepithelial
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Peripheral Nervous System Diseases
- Nervous System Neoplasms
- Osteosarcoma
- Neoplasms, Bone Tissue
- Neoplasms, Connective Tissue
- Sarcoma
- Neoplasms, Muscle Tissue
- Peripheral Nervous System Neoplasms
- Myosarcoma
- Neoplasms, Fibrous Tissue
- Fibrosarcoma
- Neurofibroma
- Neoplasms
- Recurrence
- Sarcoma, Ewing
- Neuroblastoma
- Nerve Sheath Neoplasms
- Rhabdomyosarcoma
- Neuroectodermal Tumors
- Neuroectodermal Tumors, Primitive
- Neuroectodermal Tumors, Primitive, Peripheral
- Neurofibrosarcoma
- Desmoplastic Small Round Cell Tumor
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Keratolytic Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Etoposide
- Etoposide phosphate
- Antibodies
- Podophyllotoxin
- Immunoglobulins
- Immunoglobulins, Intravenous
- Melphalan
- Fludarabine
- Fludarabine phosphate
- Tacrolimus
- gamma-Globulins
- Rho(D) Immune Globulin
- Mycophenolic Acid
- Thiotepa
- Thymoglobulin
- Antilymphocyte Serum
- Cyclosporine
- Cyclosporins
- Mechlorethamine
- Nitrogen Mustard Compounds
Other Study ID Numbers
- 2020-0496 (Other Identifier: M D Anderson Cancer Center)
- NCI-2020-05879 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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