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Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Analgesics

Anti-Infective Agents

Antirheumatic Agents

Etoposide

Mitoxantrone

Hydroxychloroquine

Etoposide phosphate

Enzyme Inhibitors

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Hydroxychloroquine + Mitoxantrone + Etoposide

Hydroxychloroquine is given up to 21 days, started concurrently with both Mitoxantrone, administered by IVPB over 15 minutes each day for 5 days and Etoposide, administered intravenously over 2 hours each day for 5 days

Doses ranging from 600-1400mg daily in divided twice daily doses and administered orally.

Dose: 100 mg/m2 administered intravenously in 500 ml of 0.9% sodium chloride

Alison Sehgal, MD

This is an open label phase I clinical trial of hydroxychloroquine (HCQ) ,when it is combined with the usual medications for acute myeloid leukemia, mitoxantrone and etoposide. The purpose of this study is to find the safest and most effective dose of hydroxychloroquine with these medications. The investigators will be testing to see if it can increase the effectiveness of mitoxantrone and etoposide.

Hydroxychloroquine is not FDA (United States Food and Drug Administration) approved for AML and is considered an investigational drug in this study. It has helped make chemotherapy more effective in animals. The investigators will be testing to see if it can increase the effectiveness of mitoxantrone and etoposide. It has been combined with other types of chemotherapy for humans with other types of cancer. Most of the patients were able to take hydroxychloroquine safely at the doses studied in this clinical trial.

Hydroxychloroquine is approved by the FDA for malaria, rheumatoid arthritis, and other autoimmune diseases. Mitoxantrone is approved by the FDA for use in AML, and it is one of the most common drugs used in the treatment of AML. Etoposide is not approved by the FDA for AML. It is approved for small cell lung cancer and testicular cancer. It is commonly used in AML.

The primary objective of this trial is to determine the recommend phase 2 dose (RP2D) for HCQ combined with mitoxantrone and etoposide, while secondary objectives include efficacy estimates of this combination at the RP2D, a safety and tolerability profile of this combination, as well as the correlation of pharmacodynamic assessments of autophagy inhibition with dose and clinical response.

Phase I Study of Mitoxantrone and Etoposide Combined With Hydroxychloroquine, for Relapsed Acute Myelogenous Leukemia

A Phase I Study of Combination Chemotherapy With Mitoxantrone and Etoposide (VP-16) Combined With an Autophagy Inhibitor, Hydroxychloroquine (HCQ), for the Treatment of Patients With Relapsed Acute Myelogenous Leukemia (AML)

Dose limiting toxicity (DLT) that occurs during the first 7 weeks after initiating therapy and is at least possibly related

Alison Sehgal, MD, MS

Assistant Professor of Medicine

Symptoms and General Pathology

Acute Disease

Disease Attributes

Micronutrients

Cytarabine

Venetoclax

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Carboplatin

Doxorubicin

Liposomal doxorubicin

Azacitidine

Decitabine

Topotecan

Daunorubicin

Thioguanine

Asparaginase

Idarubicin

Midostaurin

Sorafenib

Ivosidenib

Clofarabine

Cladribine

Iodine

Cadexomer iodine

Gemtuzumab

Iomab-B in conjunction with a Reduced Intensity Conditioning (RIC) regimen containing Fludarabine and low-dose Total Body Irradiation (TBI) prior to allogeneic HCT

Defined as Investigator's choice of salvage chemotherapy with any combination of the following agents: Azacitidine (not allowed as a single agent), Carboplatin, Cladribine, Clofarabine, Cyclophosphamide, Cytarabine, Daunorubicin, Decitabine (not allowed as a single agent with the exception of patients with documented TP53 mutations who have not previously received 10-day regimens of single agent decitabine), Doxorubicin, Enasidenib, Etoposide, Fludarabine, Gemtuzumab ozogamicin, Idarubicin, Ivosidenib (for subjects with IDH1 mutation), L-Asparaginase, Midostaurin (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Mitoxantrone, Sorafenib (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Thioguanine, Topotecan, Venetoclax (in combination with a hypomethylating agent). Chemotherapy agents not listed above may be administered after providing clinical justification and receiving medical monitor approval prior to initiation of treatment.

Iomab-B

Conventional Care

Avinash Desai, MD

The primary objective of this study is to demonstrate the efficacy of Iomab-B, in conjunction with a Reduced Intensity Conditioning (RIC) regimen and protocol-specified allogeneic hematopoietic stem cell transplant (HCT), versus Conventional Care in patients with Active, Relapsed or Refractory Acute Myeloid Leukemia (AML).

SIERRA is a pivotal Phase 3 randomized controlled study of Iomab-B in Relapsed or Refractory AML patients. The SIERRA trial has a primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival following randomization to Iomab-B, as well as Event-Free Survival. Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning.

Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia

A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplant Versus Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia (AML)

Defined as CR or CRp lasting 180 days or more from time of initial CR or CRp is documented with evidence of subsequent relapse

Duration of time from randomization to the date of induction treatment failure (ITF), relapse or death

Actinium Pharmaceuticals

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase I Study of Mitoxantrone and Etoposide Combined With Hydroxychloroquine, for Relapsed Acute Myelogenous Leukemia	NCT02631252	Leukemia, Acute...	Hydroxychloroqu... Mitoxantrone Etoposide	18 Years - 80 Years	University of Pittsburgh
Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia	NCT02665065	Acute Myeloid L... Leukemia, Acute... Myeloid Leukemi... Leukemia, Myelo... Acute Myelogeno... Leukemia, Acute... Myelogenous Leu... AML Bone Marrow Tra...	Iomab-B Conventional Ca... HCT	55 Years -	Actinium Pharmaceuticals

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