8-Chloroadenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT02509546 | Completed Phase 1 Results DMC

• 4 other identifiers: 14269NCI-2015-00871123456122489
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of 8-chloroadenosine and to see how well it works in treating patients with acute myeloid leukemia that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Drugs used in chemotherapy, such as 8-chloroadenosine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Recommended Phase II Dose (RP2D) of 8-Chloro-adenosine (8-Cl-Ado)

  According to the standard 3+3 rules, where the highest DL that produced ≤ 1/6 DLTs in cycle 1 would be defined as the maximum tolerated dose (MTD). The RP2D of 8-Cl-Ado would generally be the MTD, but it could be less than the initially calculated MTD as determined from a review of the available data and cumulative toxicities from phase 1.

  Up to 28 days following first study agent administration.

• Dose Limiting Toxicity (DLT)

  Toxicity was graded according to the NCI-Common Terminology Criteria for Adverse Events version 4.03. A DLT was defined as any of the following toxicities (please see the details in section of 13.2 of the protocol) that occur during cycle 1, per CTCAE version 4.03, and were considered related to the study drug.

  Up to 28 days following first study agent administration.

Secondary Outcomes (1)

• Complete Remission Rate (CR + CRi)

  Up to 2 years following first study agent administration.

Study Arms (6)

Phase I - 100mg/m^2 1-hour infusion

EXPERIMENTAL

100mg/m\^2 8-chloro-adenosine administered a one-hour intravenous infusion daily for first 5 days of each 28-day cycle, up to four cycles.

Drug: 8-Chloroadenosine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Phase I - 200mg/m^2 1-hour infusion

EXPERIMENTAL

200mg/m\^2 8-chloro-adenosine administered a one-hour intravenous infusion daily for first 5 days of each 28-day cycle, up to four cycles.

Drug: 8-Chloroadenosine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Phase I - 400mg/m^2 1-hour infusion

EXPERIMENTAL

400mg/m\^2 8-chloro-adenosine administered a one-hour intravenous infusion daily for first 5 days of each 28-day cycle, up to four cycles.

Drug: 8-Chloroadenosine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Phase I - 800mg/m^2 1-hour infusion

EXPERIMENTAL

800mg/m\^2 8-chloro-adenosine administered a one-hour intravenous infusion daily for first 5 days of each 28-day cycle, up to four cycles.

Drug: 8-Chloroadenosine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Phase I - 400mg/m^2 4-hour infusion

EXPERIMENTAL

400mg/m\^2 8-chloro-adenosine administered a four-hour intravenous infusion daily for first 5 days of each 28-day cycle, up to four cycles.

Drug: 8-Chloroadenosine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Phase I - 600mg/m^2 4-hour infusion

EXPERIMENTAL

600mg/m\^2 8-chloro-adenosine administered a four-hour intravenous infusion daily for first 5 days of each 28-day cycle, up to four cycles.

Drug: 8-Chloroadenosine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

8-Chloroadenosine DRUG

Given IV

Also known as: 8-Chloro-adenosine, 8-Cl-adenosine, 8-Cl-Ado

Phase I - 100mg/m^2 1-hour infusion; Phase I - 200mg/m^2 1-hour infusion; Phase I - 400mg/m^2 1-hour infusion; Phase I - 400mg/m^2 4-hour infusion; Phase I - 600mg/m^2 4-hour infusion; Phase I - 800mg/m^2 1-hour infusion

Laboratory Biomarker Analysis OTHER

Correlative studies

Phase I - 100mg/m^2 1-hour infusion; Phase I - 200mg/m^2 1-hour infusion; Phase I - 400mg/m^2 1-hour infusion; Phase I - 400mg/m^2 4-hour infusion; Phase I - 600mg/m^2 4-hour infusion; Phase I - 800mg/m^2 1-hour infusion

Pharmacological Study OTHER

Correlative studies

Phase I - 100mg/m^2 1-hour infusion; Phase I - 200mg/m^2 1-hour infusion; Phase I - 400mg/m^2 1-hour infusion; Phase I - 400mg/m^2 4-hour infusion; Phase I - 600mg/m^2 4-hour infusion; Phase I - 800mg/m^2 1-hour infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Patients must have a life expectancy of \> 3 months
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patients must have a diagnosis of AML as per World Health Organization (WHO) Classification of Hematologic Neoplasms
• Patients must meet one of the three treatment history criteria:
• Relapsed AML who have failed at least 1 line of salvage therapy
• De novo AML who have not achieved CR after 2 lines of therapy
• AML evolving from myelodysplastic syndrome (MDS) or myeloproliferative disorder who have failed hypomethylating agent or induction chemotherapy
• Patients who have relapsed after allogeneic hematopoietic cell transplant (HCT) are eligible if they are at least 3 months after HCT, do not have active graft vs. host disease (GVHD) and are off immunosuppression except for maintenance dose of steroids (prednisone 10 mg/day or less)
• At least 2 weeks from prior chemotherapy or radiation therapy to time of start of treatment, except for hydroxyurea or corticosteroid therapy which may be continued through cycle 1
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)
• Total bilirubin =\< 1.5 X ULN
• Corrected QT (QTc) =\< 480 ms
• Calculated creatinine clearance (CrCl) \>= 50 mL/min per 24 hour urine collection or the Cockcroft-Gault formula
• Negative serum or urine beta-human chorionic gonadotropin (beta-HCG) test (female of childbearing potential only), to be performed locally within the screening period

You may not qualify if:

• Current or planned use of other investigational agents, or concurrent biological chemotherapy, or radiation therapy during the study treatment period
• Expected to undergo HCT within 120 days of enrollment
• Current or planned use of agents that prolong or suspected to prolong QTc
• Diagnosis of acute promyelocytic leukemia
• Active central nervous system leukemia
• Active fungal infection or bacterial sepsis
• Active peptic ulcer disease
• History of heart failure or cardiac arrhythmia
• Other active malignancy except for localized skin cancer, bladder, prostate, breast or cervical carcinoma in situ
• Pregnant women and women who are lactating; 8-chloro-adenosine is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 8-chloro-adenosine, breastfeeding should be discontinued if the mother is treated with 8-chloro-adenosine
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

8-chloroadenosine; beta-apocarotenoid-14',13'-dioxygenase

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr. Vinod Pullarkat, MD
• Organization: City of Hope Medical Center

vpullarkat@coh.org

626-359-8111

Study Officials

• Vinod Pullarkat

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: July 28, 2015
• Study Start: September 2, 2015
• Primary Completion: March 9, 2021
• Study Completion: March 16, 2021
• Last Updated: December 5, 2023
• Results First Posted: December 5, 2023

Record last verified: 2023-11

Locations

US (1)