CompletedNCT02509546Updated Dec 5, 2023Results posted

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

A Phase 1/2 interventional study of 8-Chloroadenosine and Laboratory Biomarker Analysis in Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, sponsored by City of Hope Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-12-05.

Sponsored by City of Hope Medical Center · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 20
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (recommended phase II dose, RP2D) of 8-chloro-adenosine, when given as a single agent, in patients with relapsed or refractory acute myeloid leukemia. (Phase I) II. To assess tolerability and safety of 8-chloro-adenosine at each dose level by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (Phase I) III. To estimate the response rate and to evaluate the antitumor activity of 8-chloro-adenosine, when given as a single agent, as assessed by complete remission rate (complete remission [CR] + complete remission with incomplete blood count recovery [CRi]). (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate for disease response to 8-chloro-adenosine in refractory/relapsed acute myeloid leukemia (AML) on each dose level tested. (Phase I) II. To obtain estimates of remission duration and survival probabilities (overall and event-free). (Phase II) III. To obtain an estimate of the overall response rate (CR + CRi + partial response [PR]). (Phase II) IV. To summarize and evaluate toxicities by type, frequency, severity, attribution, time course and duration. (Phase II)

CLINICAL PHARMACOLOGY OBJECTIVES:

I. To describe the plasma, urinary and cellular pharmacokinetics of 8-chloro-adenosine and metabolites.

II. To determine the impact of 8-chloro-adenosine on cellular adenosine triphosphate (ATP) pool in AML blasts.

III. To assess the impact of 8-chloro-adenosine therapy on select short-lived messenger (m) ribonucleic acids (RNAs) and corresponding proteins in circulating AML blasts.

IV. To correlate clinical responses and toxicity with plasma/urine 8-chloro-adenosine level (pharmacokinetic [PK]), cellular 8-chloro-ATP (PK) and cellular ATP pool.

EXPLORATORY EX-VIVO MOLECULAR OBJECTIVES:

I. To determine the cytotoxicity of 8-chloro-adenosine toward leukemic progenitor cells in vitro.

II. To generate a preliminary pre-treatment RNA/micro RNA (miRNA) signature in leukemic progenitor cells, and explore its possible association with in vitro cytotoxicity to 8-chloro-adenosine.

III. To explore the possible association between the preliminary RNA/miRNA signature and clinical response to 8-chloro-adenosine.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive 8-chloro-adenosine intravenously (IV) over 4 hours on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 2 years.

Conditions studied

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

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In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 20 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.

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Lead sponsor

City of Hope Medical Center is the lead sponsor of 670 studies on the registry; 181 are open to participants now.

Of its 30 completed or terminated interventional studies of FDA-regulated products, 12 (40%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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
Agreement by females of childbearing potential and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation; the effects of study treatment on a developing fetus have the potential for teratogenic or abortifacient effects; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

Exclusion criteria

Exclusion Criteria:

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)

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 20 participants (actual)

Study arms

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

Drug8-Chloroadenosine
Given IV
Also known as: 8-Chloro-adenosine, 8-Cl-adenosine, 8-Cl-Ado
OtherLaboratory Biomarker Analysis
Correlative studies
OtherPharmacological Study
Correlative studies

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: Up to 28 days following first study agent administration.

Secondary outcomes

Complete Remission Rate (CR + CRi)
Complete remission rate (CR + CRi) based on the Döhner 2010 criteria and calculated as the percent of evaluable patients that have confirmed CR or CRi is to evaluate the antitumor activity of 8-chloro-adenosine.
Time frame: Up to 2 years following first study agent administration.

Results

Posted Dec 5, 2023

Participant flow

Participant flow — Overall Study
Milestone	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 - 800mg/m^2 1-hour Infusion	Phase I - 400mg/m^2 4-hour Infusion	Phase I - 600mg/m^2 4-hour Infusion
Started	3	3	4	2	2	6
Completed	3	3	4	2	2	6
Not completed	0	0	0	0	0	0

Outcome measures

PrimaryRecommended 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.

Time frame:: Up to 28 days following first study agent administration.
Reported as:: Number · mg/m^2

Recommended Phase II Dose (RP2D) of 8-Chloro-adenosine (8-Cl-Ado)
mg/m^2	Phase I - Treatment (8-chloro-adenosine)
Recommended Phase II Dose (RP2D) of 8-Chloro-adenosine (8-Cl-Ado)	400

PrimaryDose 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.

Time frame:: Up to 28 days following first study agent administration.
Reported as:: Count of participants · Participants

Dose Limiting Toxicity (DLT)
Participants	Phase I - 100mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 200mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 800mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 4-hour Infusion	Phase I - 600mg/m^2 8-chloro-adenosine 4-hour Infusion
Dose Limiting Toxicity (DLT)	0	0	1	2	0	2

SecondaryComplete Remission Rate (CR + CRi)

Complete remission rate (CR + CRi) based on the Döhner 2010 criteria and calculated as the percent of evaluable patients that have confirmed CR or CRi is to evaluate the antitumor activity of 8-chloro-adenosine.

Time frame:: Up to 2 years following first study agent administration.
Reported as:: Number · Percent of evaluable patients

Complete Remission Rate (CR + CRi)
Percent of evaluable patients	Phase I - 100mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 200mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 800mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 4-hour Infusion	Phase I - 600mg/m^2 8-chloro-adenosine 4-hour Infusion
Complete Remission Rate (CR + CRi)	0	0	0	0	0	0

Adverse events

Collected over Up to 2 years following first study agent administration.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase I - 100mg/m^2 8-chloro-adenosine 1-hour Infusion	3/3 (100%)	1/3 (33.3%)	3/3 (100%)
Phase I - 200mg/m^2 8-chloro-adenosine 1-hour Infusion	3/3 (100%)	1/3 (33.3%)	3/3 (100%)
Phase I - 400mg/m^2 8-chloro-adenosine 1-hour Infusion	4/4 (100%)	2/4 (50%)	4/4 (100%)
Phase I - 800mg/m^2 8-chloro-adenosine 1-hour Infusion	2/2 (100%)	2/2 (100%)	2/2 (100%)
Phase I - 400mg/m^2 8-chloro-adenosine 4-hour Infusion	2/2 (100%)	2/2 (100%)	2/2 (100%)
Phase I - 600mg/m^2 8-chloro-adenosine 4-hour Infusion	6/6 (100%)	6/6 (100%)	6/6 (100%)

Most frequent serious events

Showing 10 of 15

Most frequent serious events
Event	Phase I - 100mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 200mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 800mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 4-hour Infusion	Phase I - 600mg/m^2 8-chloro-adenosine 4-hour Infusion
CARDIAC ARRESTCardiac disorders	0/3	0/3	1/4	1/2	0/2	0/6
MULTIORGAN FAILUREGeneral disorders	0/3	0/3	0/4	0/2	1/2	1/6
SEPSISInfections and infestations	0/3	0/3	0/4	1/2	0/2	1/6
DISEASE PROGRESSIONNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/3	1/3	0/4	0/2	1/2	0/6
INVASIVE PULMONARY ASPERGILLOSISRespiratory, thoracic and mediastinal disorders	0/3	0/3	0/4	1/2	0/2	0/6
FEBRILE NEUTROPENIABlood and lymphatic system disorders	0/3	0/3	0/4	0/2	0/2	2/6
PNEUMONIARespiratory, thoracic and mediastinal disorders	1/3	0/3	0/4	0/2	0/2	0/6
LUNG INFECTIONInfections and infestations	0/3	0/3	1/4	0/2	0/2	0/6
LEUKEMIANeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/3	0/3	1/4	0/2	0/2	0/6
SUPRAVENTRICULAR TACHYCARDIACardiac disorders	0/3	0/3	0/4	0/2	0/2	1/6

Most frequent other events

Showing 10 of 196

Most frequent other events
Event	Phase I - 100mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 200mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 800mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 4-hour Infusion	Phase I - 600mg/m^2 8-chloro-adenosine 4-hour Infusion
ANEMIABlood and lymphatic system disorders	3/3	3/3	3/4	1/2	2/2	6/6
SINUS TACHYCARDIACardiac disorders	1/3	3/3	3/4	1/2	0/2	6/6
VENTRICULAR TACHYCARDIACardiac disorders	0/3	0/3	0/4	0/2	2/2	0/6
DIARRHEAGastrointestinal disorders	2/3	3/3	2/4	0/2	0/2	3/6
NAUSEAGastrointestinal disorders	1/3	2/3	3/4	2/2	1/2	4/6
FATIGUEGeneral disorders	1/3	1/3	2/4	1/2	2/2	4/6
FEVERGeneral disorders	0/3	1/3	4/4	2/2	0/2	3/6
ALANINE AMINOTRANSFERASE INCREASEDInvestigations	0/3	1/3	0/4	2/2	0/2	3/6
ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations	1/3	0/3	0/4	2/2	0/2	4/6
BLOOD BILIRUBIN INCREASEDInvestigations	3/3	3/3	2/4	2/2	2/2	6/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Phase I - 100mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 200mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 800mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 4-hour Infusion	Phase I - 600mg/m^2 8-chloro-adenosine 4-hour Infusion	Total
Median	75 (69 to 77)	54 (28 to 66)	59 (45 to 71)	56 (50 to 63)	68 (59 to 77)	70 (61 to 75)	66 (28 to 77)

Sex: Female, Male
Sex: Female, Male(Participants)	Phase I - 100mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 200mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 800mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 4-hour Infusion	Phase I - 600mg/m^2 8-chloro-adenosine 4-hour Infusion	Total
Female	1	1	3	2	1	4	12
Male	2	2	1	0	1	2	8

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Phase I - 100mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 200mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 800mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 4-hour Infusion	Phase I - 600mg/m^2 8-chloro-adenosine 4-hour Infusion	Total
Hispanic or Latino	0	2	1	1	0	3	7
Not Hispanic or Latino	3	1	3	1	2	3	13
Unknown or Not Reported	0	0	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Phase I - 100mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 200mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 800mg/m^2 8-chloro-adenosine 1-hour Infusion	Phase I - 400mg/m^2 8-chloro-adenosine 4-hour Infusion	Phase I - 600mg/m^2 8-chloro-adenosine 4-hour Infusion	Total
United States	3	3	4	2	2	6	20

Study locations

1 site

City of Hope Medical Center
Duarte, California 91010, United States

References and documents

Study documents

Protocol and statistical analysis plan · Jul 27, 2020

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 5, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02509546
Lead sponsor: City of Hope Medical Center
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Jul 28, 2015
Start date: Sep 2, 2015
Primary completion: Mar 9, 2021
Completion: Mar 16, 2021
Results posted: Dec 5, 2023
Last update: Dec 5, 2023

Study contacts

Vinod Pullarkat

principal investigator · City of Hope Medical Center

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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