Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Promyelocytic, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Acute Graft Versus Host Disease

Acute Promyelocytic Leukemia

Antineoplastic Agents

Dermatologic Agents

All Drugs and Chemicals

Tretinoin

Arsenic Trioxide

Keratolytic Agents

Remission induction therapy will be administrated as ATRA 25/mg/m2/day for 28 continuous days without interruption if APL is suspected. ATO 0.3mg/kg/day for days 1-5 (5 doses) and then 0.25 mg/kg/day every other day twice a week for the next 3 weeks (6 doses).

Patients will receive ATO 0.3mg/kg/day for days 1-5 (5 doses) and then 0.25 mg/kg/day every other day twice a week for the next 3 weeks (6 doses).

Arsenic trioxide

Patients will receive ATRA 25/mg/m2/day for 28 continuous days without interruption.

all-trans retinoic acid

Edgar Coronado-Alejandro, MD

Andrés Gómez de León, MD

David Gomez-Almaguer, MD

Andres Gomez, MD

ATRA is the standard of care for all patients with APL. The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective. In this study we intent to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO.

The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic plasma concentrations sufficient to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO alone demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective in inducing similar remission rates and achieving prolonged survival, also demonstrating a reduction in associated toxicities, mainly hepatic and cardiac when using this new scheme.

The investigators will conduct a phase 1/2, non-randomized, single center, non-comparative clinical trial to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO which is accessible to a population with limited resources while maintaining acceptable efficacy and safety.

A consecutive sample of 15 patients with newly diagnosed or relapsed APL who have not been previously treated with ATO will be prospectively included in this study.

Effectiveness and Safety of Therapy Based on Attenuated ATO Plus Low-Dose ATRA in Patients With APL

Effectiveness and Safety of Therapy Based on Attenuated Arsenic Trioxide Plus Low Doses of All-trans Retinoic Acid as Remission Induction Therapy in Patients With Acute Promyelocytic Leukemia Phase 1/2 Clinical Trial

Safety will be defined by the number of patients deceased after 1 induction cycle of 28 days

Overall response rate was definide as partial response plus complete response after 1

Time from achievement of complete hematologic remission to relapse

Time from registration to induction failure, relapse, or death.

Rate of treatment discontinuation due to toxicity.

Hospital Universitario Dr. Jose E. Gonzalez

Head of Hematology Service

Immune System Diseases

Lymphoma

Hodgkin Disease

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Antirheumatic Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Cardiotonic Agents

Anti-Infective Agents

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Bendamustine Hydrochloride

Vincristine

Prednisolone

Lenograstim

Etoposide phosphate

Brentuximab Vedotin

Methylprednisolone

Bleomycin

Vinblastine

Dacarbazine

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Dexrazoxane

Razoxane

Imidazole

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Participants receive 2 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.

Participants receive 3 cycles of BEABOVP: bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine and prednisone. For patients with an AR after 2 cycles of therapy, steroids will be omitted from their subsequent cycles of therapy. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.

Participants receive 2 cycles of AEPA: Adcedris® (brentuximab vedotin), etoposide, prednisone and Adriamycin® (doxorubicin) and 4 cycles of CAPDac: cyclophosphamide, Adcetris® (brentuximab vedotin), prednisone and Dacarbazine® (DTIC). For patients with an AR after 2 cycles of therapy, steroids will be omitted from their subsequent cycles of therapy. Filgrastim may be given as clinically indicated. Dexrazoxane may be given at the discretion of the treating investigator. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy. Quality of Life measurements may be done.

bendamustine

Filgrastim

DTIC

Quality of Life measurements may be done in low-risk cycles 1 and 2 BEABOVP, intermediate-risk cycles 1, 2 and 3 BEABOVP and high-risk cycles 1 and 2 AEPA and cycles 1, 2, 3, and 4 CAPDac. QOL may be done at year 1, 2 and 5 for all risk groups.

Quality of Life Measurements

Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy for all risk groups. Radiotherapy will be administered after completion of all chemotherapy upon hematologic count recovery.

Radiotherapy

Matthew Ehrhardt, MD, MS

Michael Link, MD

Pedro De Alarcon, MD

Jeffrey Deyo, MD, PhD

Eric Larsen, MD

Alison M. Friedman, MD

Angela M. Feraco, MD, MMSc

Christine Bolen, MD

This is a phase II study using risk and response-adapted therapy for low, intermediate and high risk classical Hodgkin lymphoma. Chemotherapy regimens will be based on risk group assignment. Low-risk and intermediate- risk patients will be treated with bendamustine, etoposide, Adriamycin® (doxorubicin), bleomycin, Oncovin® (vincristine), vinblastine, and prednisone (BEABOVP) chemotherapy. High-risk patients will receive Adcetris® (brentuximab vedotin), etoposide, prednisone and Adriamycin® (doxorubicin) (AEPA) and cyclophosphamide, Adcetris® (brentuximab vedotin), prednisone and Dacarbazine® (DTIC) (CAPDac) chemotherapy. Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an adequate response (AR) after 2 cycles of therapy for all risk groups.

PRIMARY OBJECTIVES

* To evaluate the efficacy (adequate response) after 2 cycles of BEABOVP (bendamustine substitution for mechlorethamine in the original Stanford V chemotherapy backbone) in low-risk and intermediate-risk patients with classical Hodgkin lymphoma (cHL).
* To estimate the event-free survival in high-risk patients with classical Hodgkin lymphoma (cHL).

SECONDARY OBJECTIVES

* To describe the acute hematologic and infectious toxicities of BEABOVP (bendamustine substitution for mechlorethamine in the original Stanford V chemotherapy backbone) in patients with low-risk and intermediate- risk cHL as they relate to transfusion requirements, hematopoietic growth factor support, episodes of febrile neutropenia and hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
* To describe the acute hematologic, neuropathic, and infectious toxicities of AEPA/CAPDac in patients with high-risk cHL as they relate to transfusion requirements, hematopoietic growth factor support, episodes of grade 3 and 4 sensory or motor neuropathy, episodes of febrile neutropenia and hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
* To evaluate patterns of failure in irradiated and non-irradiated patients.
* To estimate the EFS functions of LR and IR patients, and compare with those in previously published studies.
* To estimate the response rate in HR patients and compare with historical and literature rates.
* To compare response rates in LR and IR patients with historical and literature rates.
* To compare the EFS function of HR patients with that in previously published studies.

EXPLORATORY OBJECTIVES

* To evaluate the plasma pharmacokinetics of bendamustine along with predictors of its variability when used as part of BEABOVP regimen for pediatric cHL patients
* To explore the patterns and dynamics of T-cell clonality in classical Hodgkin lymphoma
* To explore the association between TARC, total metabolic tumor volume, stage, risk group and treatment response.
* To establish next generation sequencing of ctDNA as a reliable method of non-invasively profiling tumor-associated mutations in pediatric patients with HL.
* To determine if kinetics of ctDNA in patients with pediatric HL during treatment are predictive of outcome.
* To obtain baseline testing by St. Jude Lifetime Study (SJLIFE) to allow for enhanced survivorship follow-up:

  * Neurologic testing
  * Neurocognitive testing
  * Quantitative brain imaging
  * Polysomnography
  * Cardiovascular testing (valvular testing, arterial elasticity, carotid-femoral pulse wave velocity, orthostatic hypotension, heart rate variability
  * Neuropathy screening
  * Changes in body mass index composition during therapy

Low-risk and Intermediate-risk: Low-risk patients will receive 2 cycles of BEABOVP and Intermediate-risk patients will receive 3 cycles of BEABOVP.

BEABOVP regimen: Patients will receive bendamustine day 1, etoposide day 15, Adriamycin® (doxorubicin) days 1 and 15, bleomycin days 8 and 22, Oncovin® (vincristine) days 8 and 22, vinblastine days 1 and 15, and prednisone two or three times per day every other day of each cycle for a total of 14 days of steroids.

High-risk patients will receive 2 cycles of AEPA and 4 cycles of CAPDac.

AEPA regimen: Patients will receive Adcedris® (brentuximab vedotin) days 1, 8 and 15, etoposide days 1 to 5, prednisone two or three times daily days 1 to 15 and Adriamycin® (doxorubicin) days 1 and 15.

CAPDac regimen: Patients will receive cyclophosphamide days 1 and 8, Adcetris® (brentuximab vedotin) days 1 and 8, prednisone two or three times daily days 1 to 15 and Dacarbazine® (DTIC) days 1 to 3.

Residual node radiotherapy will be given at the end of all chemotherapy only to involved nodes that do not have an AR after 2 cycles of therapy for all risk groups.

Steroids will be omitted after 2 cycles for any IR or HR patient with an AR after 2 cycles of therapy.

Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17

The 70 evaluable low-risk patients enrolled will be evaluated for this objective.

The 65 evaluable intermediate-risk patients enrolled will be evaluated for this objective

Time to event defined as relapse, progression or death. The 115 evaluable high-risk patients participants enrolled will be evaluated for this objective.

According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

Local failure rate in irradiated and non-irradiated patients

Time to event defined as relapse, progression or death. The EFS for the low-risk patients and intermediate-risk patients are compared to those in HOD08 and HOD05, respectively.

Response rate of adequate response after 2 cycles of AEPA in the high-risk patients with FDG-PET compared to that after 2 cycles of AEPA in HLHR13.

Response rate of adequate response after 2 cycles of BEABOVP in the low-risk and high-risk patients with FDG-PET compared to those after 2 cycles of STANFORD V chemotherapy in HOD08 and HOD05, respectively.

Time to event defined as relapse, progression or death. The EFS for the high-risk patients is compared to those in HLHR13.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Effectiveness and Safety of Therapy Based on Attenuated ATO Plus Low-Dose ATRA in Patients With APL	NCT05497310	Promyelocytic L...	Arsenic trioxid... all-trans retin...	18 Years -	Hospital Universitario Dr. Jose E. Gonzalez
Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17	NCT03755804	Hodgkin Lymphom...	bendamustine Etoposide Doxorubicin Bleomycin Vincristine Vinblastine Prednisone Filgrastim Brentuximab Ved... Cyclophosphamid... DTIC Quality of Life... Radiotherapy	- 25 Years	St. Jude Children's Research Hospital

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