Cladribine Chemotherapy for Acute Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Medical College of Wisconsin
Disqualifiers: Acute promyelocytic leukemia, active infection, pregnancy, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This is a prospective phase II clinical study planned to be conducted at the Medical College of Wisconsin (MCW). After meeting the study criteria and enrollment, patients will be treated with a cladribine based salvage regimen and followed at periodic intervals to determine the primary and secondary objectives.
Do I need to stop my current medications for this trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug Cladribine for treating acute myeloid leukemia?
Research shows that Cladribine, when used alone or in combination with other drugs, has been effective in treating acute myeloid leukemia (AML), with complete remission rates of about 70% in newly diagnosed adults and 50% in relapsed cases. Additionally, a combination of Cladribine and Cytarabine was effective in childhood AML, with a 5-year survival rate of around 50%.
12345Is Cladribine safe for use in humans?
Cladribine has been studied for its safety in treating acute myeloid leukemia (AML) and other conditions. It has shown similar side effects to other chemotherapy regimens, including bone marrow suppression, mucositis (inflammation of the mouth and gut lining), and hair loss, but no heart-related toxicity was observed. Overall, it has a safety profile comparable to other treatments used for AML.
14678What makes the drug cladribine unique for treating acute myeloid leukemia?
Cladribine is unique because it is a purine analogue that can induce cell death in myeloid cells, showing promising complete response rates in both relapsed and newly diagnosed acute myeloid leukemia patients. It is often used in combination with other drugs like mitoxantrone to enhance its effectiveness, offering a novel approach compared to traditional treatments.
1291011Eligibility Criteria
Adults (18+) with high-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML), including those who've failed hypomethylating agents, can join. They must have an ECOG score of 0-3 and meet specific health criteria like organ function tests. Pregnant women, breastfeeding mothers, and those with uncontrolled infections or Acute Promyelocytic Leukemia are excluded.Inclusion Criteria
I can care for myself but may not be able to do heavy physical work.
I am using or willing to use effective birth control during the study.
Ability to understand a written informed consent document and the willingness to sign it
+5 more
Exclusion Criteria
I have an infection that isn't responding well to treatment.
Pregnant or breast feeding women
I have been diagnosed with Acute Promyelocytic Leukemia.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a cladribine-based salvage chemotherapy regimen, with each cycle lasting 30 days. A second cycle may be administered if necessary.
4-10 weeks
Outpatient visits as needed
Follow-up
Participants are monitored for safety, MRD negativity, and overall survival after treatment
4 years
Participant Groups
The trial is testing two chemotherapy regimens for AML/MDS: CLAG-M (Cladribine, Cytarabine, Mitoxantrone, G-CSF) and CLLDAC (Cladribine and Cytarabine). It's a phase II study to see how well these treatments work and to understand the genetic factors that affect response to therapy.
2Treatment groups
Experimental Treatment
Group I: CLLDAC regimenExperimental Treatment1 Intervention
Subject's treatment cycle is 30 days. Subject may be treated on an outpatient basis (CLLDAC arm only). In addition, subjects who fail to achieve a CR/CRi after the first 30-day cycle may receive a second cycle of CLLDAC, per the discretion of the treating physician. Subjects who receive this second cycle should begin cycle 2 no later than 49 days after cycle 1.
Group II: CLAG-M regimenExperimental Treatment1 Intervention
Subject's treatment cycle is 30 days.
Cladribine is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Leustatin for:
- Hairy cell leukemia
- Chronic lymphocytic leukemia (CLL)
- Non-Hodgkin's lymphoma
- Multiple sclerosis
🇪🇺 Approved in European Union as Litak for:
- Hairy cell leukemia
- Chronic lymphocytic leukemia (CLL)
- Non-Hodgkin's lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Froedtert & the Medical College of WisconsinMilwaukee, WI
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Who Is Running the Clinical Trial?
Medical College of WisconsinLead Sponsor
References
Revisiting the role of cladribine in acute myeloid leukemia: an improvement on past accomplishments or more old news? [2014]Originally studied in lymphoid diseases, cladribine (CdA) is an adenosine deaminase resistant analog of adenosine that was later discovered to induce myeloid cell apoptosis. The activity of CdA in myeloid malignancies was first reported in relapsed/refractory (RR) pediatric acute myeloid leukemia (AML) with complete response (CR) rates of up to 47%. Consequently, several studies have confirmed the efficacy of single agent CdA or CdA combination regimens in AML. Established CR rates for combination regimens in RR adults are approximately 50%, while CR rates for newly diagnosed (ND) adults are approximately 70% and show similar toxicity profiles to previously used regimens. Despite these promising data, many centers have yet to adopt CdA combination regimens for these difficult to treat populations. We review the pharmacology, pharmacokinetics, clinical data, and safety of CdA monotherapy and combination regimens for the management of pediatric and adult ND and RR-AML.
Long-term follow-up of Cladribine, high-dose Cytarabine, and Idarubicin as salvage treatment for relapsed acute myeloid leukemia and literature review. [2021]Outcome for relapsed acute myeloid leukemia (AML) is poor. Cladribine has activity in AML, and an enhancing effect on other cytostatic drugs thus may help overcome resistance. Here, we present the final analysis of our phase II trial evaluating safety and efficacy of cladribine, cytarabine, and idarubicin (CAI) in relapsed AML.
Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: results of the St Jude AML97 trial. [2021]Because cladribine can increase cytarabine triphosphate levels, we tested a cladribine-cytarabine combination in the St Jude AML97, trial in which this combination was administered before standard chemotherapy to 96 children with acute myeloid leukemia (AML) or myelodysplastic syndrome. Patients received a 5-day course of cladribine (9 mg/m(2) per dose) and cytarabine either as daily 2-h infusions (500 mg/m(2) per dose) (arm A) or a continuous infusion (500 mg/m(2) per day) (arm B). Ara-CTP levels and inhibition of DNA synthesis increased from day 1 to day 2, but were not different between the two arms. In addition, the median blast percentages at day 15 did not differ between arms A and B, but patients treated in arm A had shorter intervals between the initiation of the first and second courses of therapy. Thus, although there were trends toward better complete remission rates and overall survival for patients treated in arm B, the reduced efficacy of arm A may have been partially compensated by more intense timing of therapy for that group. For all patients, 5-year event-free survival and overall survival estimates were 44.1+/-5.4 and 50.0+/-5.5%. Our results suggest that cladribine in combination with continuous-infusion cytarabine is effective therapy for childhood AML.
Efficacy and safety of cladribine addition to induction treatment of newly diagnosed acute myeloid leukemia: a systematic review and meta-analysis. [2022]Compared with the 3 + 7 regimen, the cladribine-containing regimen has led to improvements in the rate of complete remission (CR) in the treatment of newly diagnosed acute myeloid leukemia (AML) patients. We conducted a systematic review and meta-analysis to investigate the overall efficacy and safety of cladribine-containing regimens in the induction treatment of newly diagnosed AML patients.
Effect of Dose Ratio on Mitoxantrone and Daunorubicin in Acute Myeloid Leukemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials. [2021]To investigate the effects of mitoxantrone and daunorubicin in induced chemotherapy on complete remission (CR), death during induction therapy, overall survival (OS), disease-free survival (DFS), and relapse in patients of all ages with acute myeloid leukemia (AML).
Mitoxantrone in the treatment of relapsed and refractory acute leukemia. [2019]Twenty-four patients with acute leukemia or blast crisis (BC) of chronic myelocytic leukemia (CML) in relapse or refractory to standard chemotherapy, were eligible for treatment with mitoxantrone. Mitoxantrone (Novantrone; dihydroxyanthracenedione) was administered in a dose of 8-13 mg/m2 on five consecutive days. Five of 20 evaluable patients were induced into complete remission, one patient achieved a partial remission. Side-effects included moderate to severe bone marrow suppression, moderate mucositis and hair loss. No cardiotoxicity was observed. We believe that mitoxantrone is an active agent in the treatment of acute leukemia and suggest further studies in combination chemotherapy.
Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape. [2020]Treatment for acute myeloid leukemia (AML) generally consists of a combination of cytarabine and an anthracycline. Although induction therapy leads to complete remission (CR) for most patients, refractoriness to chemotherapy or relapse after initial response is associated with poor outcomes. The 1-year survival rates after first relapse have been reported at 29%, declining to 11% at 5 years. Prognosis is particularly poor among older patients whose higher prevalence of unfavorable cytogenetics and high frequency of comorbidities diminish their ability to tolerate intensive chemotherapy. There is no standard of care for relapsed/refractory (R/R) AML, and no new therapies have shown consistently superior outcomes in this setting in over two decades. Vosaroxin is an anticancer quinolone derivative (AQD) that was evaluated in combination with cytarabine for the treatment of R/R AML in the randomized, double-blind, placebo-controlled, phase III VALOR study (n = 711). Compared with placebo/cytarabine, the vosaroxin/cytarabine regimen demonstrated favorable CR rates and survival in patients ⩾60 years of age, with toxicities similar to other AML regimens. Here we review outcomes of recent studies of commonly used chemotherapy regimens for the treatment of R/R AML and evaluate the results of the VALOR trial in the context of the current treatment landscape.
Cladribine combined with mitoxantrone in the treatment of blastic phase of chronic myeloid leukemia. [2013]A phase II clinical study was performed to evaluate the effectiveness and toxicity of cladribine (2-CdA) combined with mitoxantrone (CM regimen) in the treatment of chronic myeloid leukemia in blastic phase (CML BP). A total of 12 adult patients with CML BP were included in this study. 2-CdA was given at a dose 0.12 mg/kg in 2-hour iv infusion on days 1-5 and mitoxantrone 10 mg/m2 i.v. day 1. The cycles were repeated at 4 week intervals in most cases. Complete remission (CR) was defined as the presence of
Cladribine and mitoxantrone dose escalation in indolent non-Hodgkin's lymphoma. [2017]Since cladribine (2-chlorodeoxyadenosine [2-CdA]) and mitoxantrone both exhibit major activity against indolent lymphoid malignancies and have different mechanisms of action, we performed a dose-escalation study of 2-CdA and mitoxantrone in patients with alkylator-failed indolent lymphoma to determine the maximum-tolerated dose (MTD) of this combination and to make preliminary observations about efficacy.
Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma. [2013]Cladribine (2-CdA) is a purine analogue that exhibits activity against a variety of hematological malignancies and has a potent immunosuppressive effect. We therefore performed a pilot study to evaluate the feasibility of a novel 2-CdA-based reduced-intensity stem cell transplantation (RIST) regimen.
[Cladribine]. [2013]Cladribine (2-chlorodeoxyadenosine: 2-CdA) is a chlorinated purine analogue that is resistant to degradation by adenosine deaminase. Phosphorylated derivatives of 2-CdA accumulate in lymphocytes with high deoxycytidine kinase activity, resulting in DNA strand breaks and cell death. Since the cytotoxic properties of 2-CdA are independent of cell division, 2-CdA is expected to be an effective agent in the treatment of indolent lymphoid malignancy with low-growth fraction. The agent was synthesized and has been investigated extensively by researchers at the Scripps Clinic and Research Foundation in the United States. The FDA approved cladribine for use against hairy cell leukemia, in 1993, and it was approved against hairy cell leukemia and indolent B-cell lymphoma in Japan in 2002 as Leustatin (Janssen Pharma Co. Ltd., Tokyo, Japan). The efficacy, toxicity and clinical usefulness of this agent against indolent lymphoid malignancies will be described according to the data from several clinical trials conducted in the United States, European countries and Japan.