Chemotherapy + Targeted Therapy for Acute Lymphoblastic Leukemia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Washington
Must not be taking: Corticosteroids, Cytarabine
Disqualifiers: Burkitt lymphoma, CNS disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II clinical trial tests a chemotherapy regimen (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin with or without rituximab \[DA-EPOCH+/-R\]) with the addition of targeted therapy (tafasitamab) for the treatment of patients with newly diagnosed Philadelphia chromosome negative (Ph-) B acute lymphoblastic leukemia (B-ALL). Chemotherapy drugs, such as those in EPOCH+/-R, 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. Tafasitamab is in a class of medications called monoclonal antibodies. It works by helping the body to slow or stop the growth of cancer cells. Adding tafasitamab to the DA-EPOCH+/-R regimen may work better than DA-EPOCH+/-R alone in treating newly diagnosed Ph- B-ALL.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that no prior systemic therapy for ALL is allowed except to control acute symptoms, so it's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drugs used in the Chemotherapy + Targeted Therapy for Acute Lymphoblastic Leukemia trial?
Research shows that a combination of drugs including prednisone, vincristine, and etoposide (VP-16) can lead to complete remission in some children with relapsed acute lymphoblastic leukemia (ALL). Additionally, a study found that a regimen including vincristine, doxorubicin, and prednisone achieved a high complete remission rate in adults with ALL.
12345Is the combination of chemotherapy and targeted therapy for acute lymphoblastic leukemia generally safe in humans?
The research indicates that certain chemotherapy drugs like idarubicin and liposomal daunorubicin, when used in combination with other treatments, have shown low non-hematologic toxicity (side effects not related to blood) in patients with acute lymphoblastic leukemia. This suggests that these treatments can be generally safe for humans, although individual responses may vary.
678910What makes the chemotherapy and targeted therapy treatment for acute lymphoblastic leukemia unique?
This treatment combines multiple drugs, including cyclophosphamide, doxorubicin, etoposide, prednisone, and vincristine, which are used together to target leukemia cells in different ways. The combination aims to improve outcomes by using drugs with different mechanisms of action, potentially overcoming resistance seen with other treatments.
1231112Eligibility Criteria
This trial is for adults over 18 with newly-diagnosed Ph- B-ALL who can't use pediatric treatments, often due to age or other concerns. Participants need functioning kidneys and liver (with specific limits on enzyme levels), no severe blood count issues for subsequent treatment cycles, a performance status indicating they're not too sick to participate, and an expected survival beyond 3 months.Inclusion Criteria
Marrow or blood involvement detectable by MFC
Total bilirubin =< 2.0 x upper limit of normal (ULN) (unless attributed to Gilbert's disease or other causes of inherited indirect hyperbilirubinemia, at which point total bilirubin must be =< 4.0 x ULN)
I am an adult with a new diagnosis of a specific type of leukemia.
+7 more
Exclusion Criteria
May not be pregnant or nursing
I have only received emergency treatment for my acute lymphoblastic leukemia.
I have been diagnosed with Burkitt lymphoma/leukemia.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive DA-EPOCH+/-R chemotherapy and tafasitamab for up to 8 cycles, with each cycle lasting 21 days
24 weeks
Weekly visits for IV administration and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment completion
5 years
Every 3 months for 2 years, then every 6 months for 3 years
Participant Groups
The study tests DA-EPOCH+/-R chemotherapy combined with tafasitamab against the same chemo without tafasitamab in treating Ph- B-ALL. The goal is to see if adding the targeted therapy of tafasitamab improves outcomes by slowing cancer cell growth more effectively than chemotherapy alone.
1Treatment groups
Experimental Treatment
Group I: Treatment (DA-EPOCH+/-R, tafasitamab)Experimental Treatment12 Interventions
Patients receive etoposide, doxorubicin, and vincristine IV continuously over 96 hours on days 1-4 of each cycle, cyclophosphamide IV over 1 hour on day 5 of each cycle, prednisone PO BID on days 1-5 of each cycle, and tafasitamab IV weekly on days 1, 8, and 15 of each cycle. CD20 positive patients also receive rituximab IV per guidelines on days 1 or 5 of each cycle. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration or biopsy, CT scan, lumbar puncture and undergo blood sample and cerebrospinal fluid collection throughout the trial.
Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Cytoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇪🇺 Approved in European Union as Endoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇨🇦 Approved in Canada as Neosar for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇯🇵 Approved in Japan as Endoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fred Hutch/University of Washington Cancer ConsortiumSeattle, WA
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Who Is Running the Clinical Trial?
University of WashingtonLead Sponsor
Incyte CorporationIndustry Sponsor
References
Etoposide (VP-16) with prednisone and vincristine for the treatment of refractory acute lymphoblastic leukemia. [2017]Fifty children with acute lymphoblastic leukemia (ALL) in first to fifth relapse were treated with a three-drug reinduction regimen consisting of prednisone (40 mg/m2/d for seven days), vincristine (1.5 mg/m2 on day 1) and etoposide (VP-16, 250 mg/m2 on days 1 through 3). The intent was to assess the efficacy of VP-16 in an otherwise conventional reinduction plan, especially in patients who had previously received teniposide (VM-26), the close congener of VP-16. Among the 46 patients who received at least two courses of the therapy, 16 (0.34) achieved complete remission. Seven others showed improvement in their bone marrow status. Each child had been heavily pretreated with prednisone and vincristine, and 14 had received VM-26. That seven patients judged to be clinically resistant to VM-26 had complete responses to prednisone-vincristine-VP-16 indicates that prior treatment with one podophyllotoxin derivative does not preclude responses to the other. We are uncertain about the pharmacologic basis of these results but suggest that the increased dosage and more frequent administration of VP-16, relative to that of VM-26, was sufficient to overcome apparent resistance to the latter compound. Remission durations ranged from one to eight months (median, four months), emphasizing the need to devise more effective continuation therapy, including investigational agents such as the epipodophyllotoxins.
Ifosfamide and etoposide in recurrent childhood acute lymphoblastic leukemia. [2019]The activity of the drug combination ifosfamide and etoposide (VP16) in refractory and relapsed childhood acute lymphoblastic leukemia (ALL) was assessed in a phase II study.
Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study. [2021]Children with acute lymphoblastic leukemia (ALL) who have completed 2.5 to 3 years of initial chemotherapy have an off-therapy relapse rate of approximately 20%. In an attempt to improve the survival of children with a late bone marrow (BM) relapse (ie, occurring greater than 6 months after cessation of primary therapy), the Pediatric Oncology Group designed a randomized study to compare the efficacy of doxorubicin/prednisone and cytarabine/teniposide in a multidrug retreatment chemotherapy program. Treatment consisted of remission reinduction with vincristine, prednisone, and doxorubicin, central nervous system prophylaxis with triple intrathecal chemotherapy, and continuation therapy (for 132 weeks) with alternating cycles of oral 6-mercaptopurine/methotrexate and intravenous vincristine/cyclophosphamide. Patients received intermittent courses of either prednisone/doxorubicin (regimen 1) or teniposide/cytarabine (regimen 2) during continuation therapy and a late intensification phase with either vincristine, prednisone, and doxorubicin (regimen 1) or teniposide and cytarabine (regimen 2). One hundred two of 105 evaluable patients (97%) achieved a second complete remission. Twenty-eight of 50 patients on regimen 1 have failed compared with 28 or 52 patients on regimen 2 (log-rank analysis, P = .68), indicating that this trial was inconclusive as to which treatment regimen was superior. The overall 4-year event-free survival for children with a late BM relapse was 37% +/- 6%. Age less than 10 years at initial diagnosis (P
Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse. [2015]The authors evaluated the response rate, toxicity, and pharmacokinetics of topotecan given before standard induction therapy for childhood acute lymphoblastic leukemia (ALL) in first relapse.
Persistence of peripheral blood and bone marrow blasts during remission induction in adult acute lymphoblastic leukemia confers a poor prognosis depending on treatment intensity. [2015]Our objectives were to evaluate the prognostic implications of persistence of peripheral blood blasts on day 7 (D7PBb) and of bone marrow blasts >5% on day 14 (D14Mb) after initiation of induction chemotherapy in adults with acute lymphoblastic leukemia (ALL) treated with two different chemotherapy regimens. Records of 365 consecutive newly diagnosed adult ALL patients treated with: (a) vincristine-, doxorubicin-, and dexamethasone-based chemotherapy (VAD, n = 219; 1984-1992); or (b) fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with methotrexate/high-dose cytarabine (HCVAD, n = 146; 1993-1996), were analyzed. The complete remission (CR) rates were 73% with VAD and 91% with HCVAD (P
A single high dose of idarubicin combined with high-dose ARA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University "La Sapienza" of Rome. [2013]The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance.
A single high dose of idarubicin combined with high-dose ABA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University La Sapienza of Rome. [2013]The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance.
Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group. [2013]Prognosis is poor for Ewing sarcoma patients with metastasis at diagnosis. We intensified a five-drug therapy (ifosfamide, etoposide alternated with vincristine, doxorubicin, and cyclophosphamide) using filgrastim but not stem-cell support. We studied topotecan alone and combined with cyclophosphamide in therapeutic windows before the five-drug therapy. A randomly assigned proportion of patients received amifostine as a cytoprotective agent.
Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia. [2013]Toxicity limits the use of anthracyclines in elderly sick patients and in heavily pretreated patients. Since the liposomal preparation of daunorubicin (DNR) (DaunoXome, or DNX) is expected to be less toxic than conventional DNR, we tested DNX combined with high-dose arabinosyl cytosine (HDAC) in 42 adult poor-risk acute leukemia patients. Thirty-one patients had acute non-lymphocytic leukemia (ANLL). Of these, 12 patients were newly diagnosed but were not eligible for standard induction treatment, 13 were in first relapse, and 6 were in second or subsequent relapse. Eleven patients had acute lymphocytic leukemia (ALL), in first (eight cases) or second (three cases) relapse. DNX was given i.v. in three doses of 80 or 100 mg/m(2) each (days 1-3) by a 60-min infusion in glucose 5%, followed by a 4-h infusion of HDAC 2 g/m(2) (days 1-5). Among 31 ANLL patients there were 16 (51%) complete remissions (CR), 5 deaths during induction, and 10 failures. Among 11 ALL patients there were 10 CRs and 1 failure. The response rate was not affected by the overexpression of MDR-related proteins (PgP, MRP-1, and LRP). Non-hemopoietic toxicity was negligible, with no intestinal toxicity and only one case of gram-negative bacteremia. We conclude that DNX, in combination with HDAC, is an effective treatment for poor-risk adult AL. Because of the low non-hematologic toxicity, it can be used to reinduce remission in poor-risk patients who are candidates for allogeneic bone marrow transplantation. The high CR rate observed in ALL requires confirmation.
Antineoplastic agents for pediatric anaplastic large cell lymphoma: Vinblastine is the most effective in vitro. [2019]Anti-neoplastic effects of a total of 11 agents (adriamycin, briplatin, cytarabine, dexamethasone, etoposide, 4-hydroperoxycyclophosphamide, 4-hydroperoxyifosphamide, methotrexate, predonisolone, vinblastine, vincristine) were tested on 4 cell lines (DEL, Ki-JK, SR-786, SU-DHL-1) established from pediatric ALCL cases. The individual cell lines were treated with those agents at different concentrations (0.01 microM/L, 0.1 microM/L, 1 microM/L, 10 microM/L, 100 microM/L) for 1 h or 24 h, and their cellular growths were measured by the microculture tetrozolium (MTT) assay. Of those anti-neoplastic agents, methotrexate, vinblastine, and vincristine were highly effective on the cell growth inhibition in all these cell lines with time- and dose-dependent manner. Among them, vinblastine was found to be the most effective in 3 cell lines (DEL, Ki-JK, SR786) with 50% effective doses (ED50, concentrations causing 50% cell survival after treatment) ranging from 0.0016 to 1.27 microM/L for the 1-h treatment and 0.0002 - 0.59 microM/L for the 24-h treatment. Further experiments demonstrated that vinblastine treatment induced cellular apoptosis and caused severe disruption in mitotic spindle formation on these cell lines. The results support the protocol of ALCL 99 study, which uses vinblastine as one of the first-line anti-neoplastic agents for the high-risk ALCL patients in the pediatric age group.
[Study of tumor cells sensitivity in patients with acute leukemia to cytokines and their combined use with drugs in vitro by MTT analysis]. [2016]MTT analysis has yielded data on the sensitivity of leukemia cells isolated from 64 patients with acute leukemia to the cytokines G-KSF?, GM-KSF, interferon-alpha 2b and their combined use with drugs, such as cytosar, vepeside, doxorubicin, vincrastine, L-asparaginase. The mean in vitro survival of leukemia cells in children with acute lymphoblast cell leukemia (ALCL) was 1.9 times less than that in acute myeloblast cell leukemia (AMCL) (p
Treatment of acute lymphoblastic leukemia in children. Long-term results of two trials. [2007]Eighty-eight children younger than 15 years with acute lymphoblastic leukemia were treated with two similar protocols. Both regimens consist of multidrug combinations, with CNS prophylaxis. Sixty-four patients were enrolled on first protocol 0171 with vincristine and prednisone induction therapy. After remission induction patients were randomized on two arms: regimen A which consists of intensive courses of methotrexate with vincristine and prednisone reinductions and administration of cyclophosphamide. Regimen B is similar to regimen A, only courses of methotrexate are alternated with courses of 6-mercaptopurine during consolidation and intensification therapy. In maintenance phase both regimens have daily administration of 6-mercaptopurine and twice weekly administration of methotrexate, with vincristine and prednisone reinductions. The second protocol 0276/A is similar to regimen B of protocol 0171, but L-asparaginase is administered in the end of induction phase and total duration of therapy since induction of complete remission is prolonged from 2.5 to 4 years. Complete remission rate ranged from 92 to 96% in the patients achieving complete remission. In protocol 0171 actuarial proportion of children alive in complete remission for more than 10 years is 60% at present. The actual median survival of all children treated with protocol 0171 is 46+ months and actual median duration of complete remission is 43+ months. There was no significant difference between patients treated with methotrexate alone and those treated with combination of methotrexate and 6-mercaptopurine during consolidation and intensification phase. In protocol 0171 the relapse rate was 28% and the death rate in complete remission was 15%. More than 70% of complete responders in protocol 0276 is in continuous complete remission from 2+ to 57+ months, relapse rate is only 4% at present and the death rate in complete remission is 9% in this protocol.