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A Study of Venetoclax in Combination With Chemotherapy to Treat Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

Primary Purpose

Acute Lymphoblastic Leukemia

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Venetoclax

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Venetoclax, 21-372

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult patients with newly diagnosed Philadelphia chromosome (Ph) negative ALL.
Patients with T- or B-cell lymphoblastic lymphoma with no bone marrow involvement will also be eligible for the study.
Age 18-60
ECOG performance status of 0-2
Adequate renal function as demonstrated by a calculated creatinine clearance of ≥ 60 ml/min.
Adequate hepatic function as demonstrated by a total bilirubin ≤ 2.0 mg/dl (unless attributable to Gilbert's disease) and an alkaline phosphatase, AST, and ALT ≤ 4 times the upper limit of normal (unless clinically considered to be related to liver involvement with leukemia)
Patients with central nervous system (CNS) involvement by ALL are eligible and may receive concomitant treatment with radiation therapy and/or intrathecal chemotherapy in accordance with standard medical practice. For patients with CNS disease, dexamethasone may be temporarily administered instead of prednisone to reduce CNS pressure, at the discretion of the treating physician and after discussion with the MSK PI. Once dexamethasone is no longer needed, prednisone should be given as per protocol for 28 days.
Negative serum pregnancy test in women of childbearing potential

Exclusion Criteria:

CML in lymphoid blast crisis, mature B-cell (i.e. Burkitt's) lymphoma or mixed phenotype acute leukemia (MPAL)
Prior treatments for ALL, except any doses of corticosteroids and hydroxyurea or one dose of vincristine
Patients who received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment
Unstable angina and/or MI or stroke within 6 months prior to screening, and/or impaired cardiac function with EF <40% or NYHA class III/IV
Pregnant or lactating women. Women and men of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished.
Patients with HIV or active hepatitis B or hepatitis C infection are ineligible.
Patients with concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of the skin, in situ cervical cancer, adequately treated stage I/II cancer from which the patient is current in complete remission, or any other cancer from which the patient has been disease free for five years.

Sites / Locations

Memorial Sloan Kettering Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Venetoclax in Combination With Chemotherapy

Arm Description

All patients will complete Induction I and II of the treatment regimens, consisting of several chemotherapy agents including Peg-ASP.

Outcomes

Primary Outcome Measures

proportion of patients who have a Dose Limiting Toxicities

Secondary Outcome Measures

Full Information

NCT ID

NCT05386576

First Posted

May 18, 2022

Last Updated

February 2, 2023

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05386576

Brief Title

A Study of Venetoclax in Combination With Chemotherapy to Treat Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

Official Title

Venetoclax in Combination With Asparaginase-Containing Pediatric-Inspired Chemotherapy in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 16, 2022 (Actual)

Primary Completion Date

May 2024 (Anticipated)

Study Completion Date

May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The researchers are doing this study to find out whether combining venetoclax with several different standard chemotherapy drugs used to treat acute lymphoblastic leukemia (ALL) in children is safe and effective in adults with newly diagnosed ALL. Participants in this study will be under the age of 60, and they will have T- or B-cell ALL.

Detailed Description

All patients will complete Induction I and II of the treatment regimens, consisting of several chemotherapy agents including Peg-ASP. For Dose Level 1: Venetoclax will be administered at a dose of 100mg on day 5, 200mg on day 6 and 400mg on days 7-28 during Induction I. During Induction II, venetoclax will be administered at 400mg daily from days 1-14 and 29-42. For Dose Level -1: Venetoclax will be administered at a dose of 100mg on day 5 and 200mg on days 6-28 during Induction I. During Induction II, venetoclax will be administered at 200mg daily from days 1-14 and 29-42. Bone marrow aspirate and biopsy will be performed at day 14 of Induction I, after Induction I and Induction II for disease assessment. For those who remain on study after Induction II, they will proceed to consolidation therapy. Consolidation blocks contain 2 Intensification blocks (22 days each) and 2 Re-Induction blocks (43 days each), consisting of several chemotherapy agents including Peg-ASP. Venetoclax will be administered at a dose of 400mg daily (Dose Level 1) or 200mg daily (Dose Level -1) from days 1-22 during Intensification blocks, and from days 1-14 and 29-42 during Re-Induction blocks. Bone marrow aspirate and biopsy will be performed after Re-Induction I and Re-Induction II for disease assessment. Patients who relapse either with MRD or morphologically will be removed from study to pursue alternative therapy. Patients who remain in MRD negative CR will remain on study and proceed to Maintenance. Maintenance block contains 4-drug regimen (vincristine, oral methotrexate, oral mercaptopurine, and prednisone) for 2 years. No venetoclax will be administered during this block. Bone marrow aspirate and biopsy will be performed every 3 months during the Maintenance block. Patients who remain in MRD negative CR will remain on study to complete the study treatment. Patients who relapse either with MRD or morphologically will be removed from study to pursue alternative therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lymphoblastic Leukemia

Keywords

Venetoclax, 21-372

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Model Description

This is a phase I single-arm, single-center study.

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Venetoclax in Combination With Chemotherapy

Arm Type

Experimental

Arm Description

All patients will complete Induction I and II of the treatment regimens, consisting of several chemotherapy agents including Peg-ASP.

Intervention Type

Drug

Intervention Name(s)

Venetoclax

Intervention Description

During Induction I, for patients on Dose Level 1, venetoclax will be administered at a dose of 100mg on day 5, 200mg on day 6 and 400mg on days 7-28. For patients on Dose Level 01, venetoclax will be administered at a dose of 100mg on day 5 and 200mg on days 6-28. During Induction II, venetoclax will be administered at either 400mg daily (Dose Level 1) or 200mg daily (Dose Level -1) from days 1-14 and 29-42.

Primary Outcome Measure Information:

Title

proportion of patients who have a Dose Limiting Toxicities

Time Frame

up to 6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult patients with newly diagnosed Philadelphia chromosome (Ph) negative ALL. Patients with T- or B-cell lymphoblastic lymphoma with no bone marrow involvement will also be eligible for the study. Age 18-60 ECOG performance status of 0-2 Adequate renal function as demonstrated by a calculated creatinine clearance of ≥ 60 ml/min. Adequate hepatic function as demonstrated by a total bilirubin ≤ 2.0 mg/dl (unless attributable to Gilbert's disease) and an alkaline phosphatase, AST, and ALT ≤ 4 times the upper limit of normal (unless clinically considered to be related to liver involvement with leukemia) Patients with central nervous system (CNS) involvement by ALL are eligible and may receive concomitant treatment with radiation therapy and/or intrathecal chemotherapy in accordance with standard medical practice. For patients with CNS disease, dexamethasone may be temporarily administered instead of prednisone to reduce CNS pressure, at the discretion of the treating physician and after discussion with the MSK PI. Once dexamethasone is no longer needed, prednisone should be given as per protocol for 28 days. Negative serum pregnancy test in women of childbearing potential Exclusion Criteria: CML in lymphoid blast crisis, mature B-cell (i.e. Burkitt's) lymphoma or mixed phenotype acute leukemia (MPAL) Prior treatments for ALL, except any doses of corticosteroids and hydroxyurea or one dose of vincristine Patients who received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment Unstable angina and/or MI or stroke within 6 months prior to screening, and/or impaired cardiac function with EF <40% or NYHA class III/IV Pregnant or lactating women. Women and men of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished. Patients with HIV or active hepatitis B or hepatitis C infection are ineligible. Patients with concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of the skin, in situ cervical cancer, adequately treated stage I/II cancer from which the patient is current in complete remission, or any other cancer from which the patient has been disease free for five years.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jae Park, MD

Phone

646-608-3743

parkj6@mskcc.org

First Name & Middle Initial & Last Name or Official Title & Degree

Mark Geyer, MD

Phone

646-608-3745

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jae Park, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jae Park, MD

Phone

646-608-3743

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Links:

URL

http://www.mskcc.org/mskcc/html/44.cfm

Description

Memorial Sloan Kettering Cancer Center

Learn more about this trial

A Study of Venetoclax in Combination With Chemotherapy to Treat Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

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