Low-Intensity Chemotherapy and Venetoclax in Treating Patients With Relapsed or Refractory B- or T-Cell Acute Lymphoblastic Leukemia
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| ClinicalTrials.gov Identifier: NCT03808610 |
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Recruitment Status :
Recruiting
First Posted : January 17, 2019
Last Update Posted : November 7, 2023
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Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
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Brief Summary:
This phase I/II trial studies the side effects and best dose of venetoclax and how well it works in combination with low-intensity chemotherapy in patients with B- or T-cell acute lymphoblastic leukemia that has not responded to treatment or that has come back. Venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, including vincristine, cyclophosphamide, dexamethasone, rituximab, methotrexate, and cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax with low-intensity chemotherapy may work better in treating patient with B- or T-cell acute lymphoblastic leukemia.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Recurrent B Acute Lymphoblastic Leukemia Recurrent T Acute Lymphoblastic Leukemia Refractory B Acute Lymphoblastic Leukemia Refractory T Acute Lymphoblastic Leukemia | Drug: Cyclophosphamide Drug: Cytarabine Drug: Dexamethasone Drug: Methotrexate Drug: Nelarabine Drug: Pegaspargase Drug: Prednisone Biological: Rituximab Drug: Venetoclax Drug: Vincristine | Phase 1 Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 50 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase I/II Study of the Combination of Low-Intensity Chemotherapy and Venetoclax (ABT-199) in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) |
| Actual Study Start Date : | April 3, 2019 |
| Estimated Primary Completion Date : | December 31, 2026 |
| Estimated Study Completion Date : | December 31, 2026 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Venetoclax
| Arm | Intervention/treatment |
|---|---|
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Experimental: Experimental (venetoclax, vincristine, cyclophosphamide)
See Detailed Description.
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Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine Given IV
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Methotrexate Given IV
Other Names:
Drug: Nelarabine Given IV
Other Names:
Drug: Pegaspargase Given IV
Other Names:
Drug: Prednisone Given PO
Other Names:
Biological: Rituximab Given IV
Other Names:
Drug: Venetoclax Given PO
Other Names:
Drug: Vincristine Given IV
Other Names:
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Primary Outcome Measures :
- Maximum tolerated dose (MTD) (Phase I) [ Time Frame: Up to 28 days ]The MTD is the highest dose level in which < 2 patients of 6 develop first cycle dose-limiting toxicity (DLT).
- DLT (Phase I) [ Time Frame: Up to 28 days ]A non-hematologic DLT is defined as a clinically significant (as assessed by treating physician) grade 3 or 4 adverse event or abnormal laboratory value (according to Common Terminology Criteria for Adverse Events [CTCAE] criteria). Toxicity type, severity and attribution will be summarized for each patient using frequency tables.
Secondary Outcome Measures :
- Overall response rate (Phase II) [ Time Frame: Up to 56 days (2 courses) ]Will be defined as the percentage of patients achieving a complete response (CR) or CR with inadequate count recovery (CRi). Will estimate the overall response (OR) for the combination treatment, along with the 95% credible interval.
- Minimal residual disease (MRD) negativity [ Time Frame: Up to 4 years ]Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
- Duration of response (DOR) [ Time Frame: Up to 4 years ]Will be summarized using descriptive statistics such as mean, standard deviation, median and range. The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
- Event-free survival (EFS) [ Time Frame: From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 4 years ]The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
- Overall survival (OS) [ Time Frame: From the first day of treatment to time of death from any cause, assessed up to 4 years ]The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
- Incidence of adverse events [ Time Frame: Up to 4 years ]Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
Other Outcome Measures:
- Apoptotic protein expression and Bcl-2 dependency [ Time Frame: Up to 4 years ]Apoptotic protein expression and Bcl-2 dependency will be correlated on response and resistance to the combination regimen.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients with relapsed/refractory B- or T-cell ALL
- Performance status =< 3 (Eastern Cooperative Oncology Group [ECOG] Scale)
- Total serum bilirubin =< 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome, in which case patients are eligible as long as direct bilirubin =< 2 x ULN
- Alanine aminotransferase (ALT) =< 3 x ULN, unless due to disease involvement of the liver or hemolysis, in which case an ALT =< 10 x ULN is acceptable
- Aspartate aminotransferase (AST) =< 3 x ULN, unless due to disease involvement of the liver or hemolysis, in which case an AST =< 10 x ULN is acceptable
- Creatinine clearance >= 30 mL/min
- For females of childbearing potential, a negative pregnancy test must be documented within 1 week of starting treatment
- Female and male patients who are fertile must agree to use an effective form of contraception (birth control methods while on study, such as birth control pills or injections, intrauterine devices [IUDs]), or double-barrier methods (for example, a condom in combination with spermicide) with their sexual partners for 4 months after the end of treatment
- Signed informed consent
Exclusion Criteria:
- Patients with Philadelphia chromosome-positive ALL or Burkitt leukemia
- Active serious infection not controlled by oral or intravenous antibiotics
- Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma) that in the investigator's opinion will shorten survival to less than 1 year
- Known hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
- Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
- Patients with a cardiac ejection fraction (as measured by either multigated acquisition [MUGA] or echocardiogram) < 40%
- Received moderate or strong CYP3A inhibitors or strong CYP3A inducers within 7 days of starting venetoclax
- Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax
- Prior history of treatment with venetoclax
- Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator. Exception: Treatment with hydroxyurea and/or dexamethasone are allowed prior to study treatment, without window of exclusion
- Pregnant and lactating women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception. Women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control
- History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease); diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03808610
Contacts
| Contact: Elias Jabbour | 713-792-4764 | ejabbour@mdanderson.org |
Locations
| United States, Texas | |
| M D Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Elias Jabbour 713-792-4764 | |
| Principal Investigator: Elias Jabbour | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Elias Jabbour | M.D. Anderson Cancer Center |
Additional Information:
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT03808610 |
| Other Study ID Numbers: |
2016-0629 NCI-2018-03360 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2016-0629 ( Other Identifier: M D Anderson Cancer Center ) |
| First Posted: | January 17, 2019 Key Record Dates |
| Last Update Posted: | November 7, 2023 |
| Last Verified: | November 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Recurrence Neoplasms by Histologic Type Neoplasms Disease Attributes Pathologic Processes Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine 6-methoxypurine arabinoside |
Dexamethasone Dexamethasone acetate Prednisone Cortisone Cyclophosphamide Rituximab Methotrexate Vincristine Venetoclax Asparaginase Pegaspargase Antineoplastic Agents, Immunological Antibodies Immunoglobulins Antibodies, Monoclonal |