Donor Stem Cell Transplant After Chemotherapy for the Treatment of Recurrent or Refractory High-Risk Solid Tumors in Pediatric and Adolescent-Young Adults
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| ClinicalTrials.gov Identifier: NCT04530487 |
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Recruitment Status :
Recruiting
First Posted : August 28, 2020
Last Update Posted : February 21, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Drug: Cyclosporine Drug: Etoposide Drug: Fludarabine Phosphate Biological: Lapine T-Lymphocyte Immune Globulin Drug: Melphalan Drug: Mycophenolate Mofetil Drug: Tacrolimus Drug: Thiotepa | Phase 2 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 40 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric and Adolescent-Young Adults Patients With High Risk Solid Tumors |
| Actual Study Start Date : | August 19, 2020 |
| Estimated Primary Completion Date : | May 9, 2025 |
| Estimated Study Completion Date : | May 9, 2025 |
| Arm | Intervention/treatment |
|---|---|
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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. |
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo HSCT
Other Names:
Drug: Cyclosporine Given IV and PO
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Fludarabine Phosphate Given IV
Other Names:
Biological: Lapine T-Lymphocyte Immune Globulin Given IV
Other Names:
Drug: Melphalan Given IV
Other Names:
Drug: Mycophenolate Mofetil Given IV or PO
Other Names:
Drug: Tacrolimus Given IV and PO
Other Names:
Drug: Thiotepa Given IV
Other Names:
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- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- Progression-free survival (PFS) [ Time Frame: At 180 days post transplant ]Will be assessed using the method of Kaplan and Meier.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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| Ages Eligible for Study: | up to 25 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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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)
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04530487
| Contact: Kris M Mahadeo | 713-792-6610 | kmmahadeo@mdanderson.org |
| United States, Texas | |
| M D Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Kris M. Mahadeo 713-792-6610 | |
| Principal Investigator: Kris M. Mahadeo | |
| Principal Investigator: | Kris M Mahadeo | M.D. Anderson Cancer Center |
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT04530487 |
| Other Study ID Numbers: |
2020-0496 NCI-2020-05879 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2020-0496 ( Other Identifier: M D Anderson Cancer Center ) |
| First Posted: | August 28, 2020 Key Record Dates |
| Last Update Posted: | February 21, 2021 |
| Last Verified: | February 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Neoplasms Neuroblastoma Rhabdomyosarcoma Sarcoma, Ewing Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neuroectodermal Tumors, Primitive, Peripheral Nerve Sheath Neoplasms Neurofibrosarcoma Desmoplastic Small Round Cell Tumor Sarcoma Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms, Neuroepithelial Neoplasms, Germ Cell and Embryonal |
Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Myosarcoma Neoplasms, Muscle Tissue Osteosarcoma Neoplasms, Bone Tissue Neoplasms, Connective Tissue Peripheral Nervous System Neoplasms Nervous System Neoplasms Nervous System Diseases Peripheral Nervous System Diseases Neuromuscular Diseases Fibrosarcoma Neoplasms, Fibrous Tissue Neurofibroma |