Hyper-CVAD With Liposomal Vincristine in Acute Lymphoblastic Leukemia

NCT01319981 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2008-0598NCI-2011-00861
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. The goal of this clinical research study is to learn if intensive chemotherapy (hyper-CVAD therapy) given in combination with liposomal vincristine (Marqibo), in addition to rituximab for patients who are CD20 positive and/or imatinib, dasatinib, or ruxolitinib for patients with the Philadelphia (Ph) chromosome, can help to control ALL or lymphoblastic lymphoma. The safety of this treatment will also be studied. CD20 is a protein "marker" that is found in leukemia or lymphoma cells. This is an investigational study. Liposomal vincristine is FDA approved for the treatment of patients with CLL who have relapsed at least 2 times. All of the other study drugs used in this study are FDA approved and commercially available. The combination of liposomal vincristine with the other study drugs is also being used in research only. Up to 65 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions

Leukemia

Keywords

Acute Lymphoblastic Leukemia; ALL; Lymphoblastic lymphoma; Cytoxan; Neosar; Mesnex; Liposomal Vincristine; Vincristine Sulfate Liposomes Injection; Marqibo; Dexamethasone; Adriamycin; Rubex; Cytarabine; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride; Imatinib Mesylate; Gleevec; ST1571; NSC-716051; Filgrastim; Neupogen

Outcome Measures

Primary Outcomes (3)

• Number of Patients With Complete Remission at One Year

  The complete remission (CR) is the total number of patients who are in CR at one year divided by the total number of patients who received at least one dose of HCVAD with liposomal vincristine. CR was defined as the presence of \</=5% blasts in the bone marrow, with \>1x10\^9/L neutrophils, \>100x10\^9/L platelets in the perpherial blood, and no extramedullary disease.

  1 year

• Overall Survival

  Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis.

  Up to 7 years, 8 months

• Complete Response Duration

  The complete remission (CR) is the total number of patients who are in CR at one year divided by the total number of patients who received at least one dose of HCVAD with liposomal vincristine. CR was defined as the presence of \</=5% blasts in the bone marrow, with \>1x10\^9/L neutrophils, \>100x10\^9/L platelets in the perpherial blood, and no extramedullary disease. Response date to loss of response or last follow up. Remission duration will be measured by the estimated median remission duration computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative remission duration drops below 50%, if present. If not present then median remission duration is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis..

  Up to 7 years, 8 months

Study Arms (2)

Hyper-CMAD + Rituximab

EXPERIMENTAL

Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 \& 8 Courses 1 \& 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 \& 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days.

Drug: Rituximab; Drug: Imatinib; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Mesna; Drug: VSLI; Drug: G-CSF; Drug: Pegfilgrastim; Drug: Dexamethasone

Hyper-CMAD

EXPERIMENTAL

Courses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 \& 8 Courses 2 \& 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day.

Drug: Rituximab; Drug: Imatinib; Drug: VSLI; Drug: Solu-Medrol; Drug: Methotrexate; Drug: Ara-C; Drug: G-CSF; Drug: Pegfilgrastim

Interventions

Rituximab DRUG

In CD20-positive patients, 375 mg/m2 by vein on day 1 and 8 for Courses 1 and 3; and day 1 and 8 of Courses 2 and 4.

Also known as: Rituxan

Hyper-CMAD; Hyper-CMAD + Rituximab

Imatinib DRUG

600 mg by mouth daily days 1-14 for course 1 and continuously on all other courses for patients who are Philadelphia chromosome positive (Ph+).

Also known as: Imatinib Mesylate, Gleevec, ST1571, NSC-716051

Hyper-CMAD; Hyper-CMAD + Rituximab

Cyclophosphamide DRUG

300 mg/m2 by vein over 3 hours every 12 hours x 6 doses days 1, 2, 3 (total dose 1800 mg/m2) for courses 1, 3, 5, 7

Also known as: Cytoxan, Neosar

Hyper-CMAD + Rituximab

Doxorubicin DRUG

50 mg/m2 by vein over 24 hours on day 4 after last dose of Cyclophosphamide for courses 1, 3, 5, 7

Also known as: Adriamycin, Rubex

Hyper-CMAD + Rituximab

Mesna DRUG

600 mg/m2 by vein continuous infusion daily for 24 hours days 1-3 for courses 1, 3, 5, 7

Also known as: Mesnex

Hyper-CMAD + Rituximab

VSLI DRUG

2.0 mg/m2 by vein on day 1 and day 8 for courses 1, 3, 5, 7

Also known as: Liposomal Vincristine, Vincristine Sulfate Liposomes Injection, Marqibo

Hyper-CMAD; Hyper-CMAD + Rituximab

Solu-Medrol DRUG

40 mg by vein every 12 hours for 6 doses days 1-3 for courses 2, 4, 6, 8.

Also known as: Methylprednisolone, Depo-Medrol, Medrol

Hyper-CMAD

Methotrexate DRUG

200 mg/m2 IV over 2 hrs followed by 800 mg/m2 over 22 hrs on day 1 beginning after the completion of rituximab for Courses 2, 4, 6, and 8.

Hyper-CMAD

Ara-C DRUG

3 gm/m2 by vein over 2 hours every 12 hours for 4 doses on days 2, 3 for Courses 2, 4, 6, and 8.

Also known as: Cytarabine, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

Hyper-CMAD

G-CSF DRUG

10 µg/kg/day (rounded) given subcutaneously until neutrophil recovery to 1 x 10\^9/L or higher can be substituted or can be added if neutrophils have not recovered to 1 x 10\^9/L by day 21.

Also known as: Filgrastim, Neupogen

Hyper-CMAD; Hyper-CMAD + Rituximab

Pegfilgrastim DRUG

6 mg/kg (rounded) within 72 hrs after completion of chemotherapy.

Also known as: Neulasta

Hyper-CMAD; Hyper-CMAD + Rituximab

Dexamethasone DRUG

40 mg by vein or by mouth daily days 1-4 and days 11-14 for courses 1, 3, 5, 7

Also known as: Decadron

Hyper-CMAD + Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed previously untreated ALL or lymphoblastic lymphoma \>/= 18 years old. Allow urgent administration of cytarabine/hydrea/atra prior to starting treatment on protocol. Allow previous administration of up to one course of Hyper-CVAD and/or FDA approved TKI.
• Zubrod performance status \</= 3.
• Adequate liver function (bilirubin \</= 3.0 mg/dl unless considered due to tumor) and renal function (creatinine \</= 3.0 mg/dl, unless considered due to tumor).
• No active co-existing malignancy with life expectancy less than 12 months due to that malignancy.
• All men and women of childbearing potential who are participating in the study must agree to use effective forms of birth control throughout the duration of their treatment.
• Adequate cardiac function as assessed clinically

You may not qualify if:

• Pregnant or lactating women. Women of childbearing potential (WOCB) must have a blood or urine pregnancy test within 7 days prior to administration of the study drug. (WOCB is defined as a woman who has not undergone hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 24 consecutive months).
• Active Grade III-IV cardiac failure as defined by the New York Heart Association criteria, uncontrolled angina or MI within 6 months.
• Patients with medical conditions that compromise their ability to complete the study or confound interpretation of study results.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Spectrum Pharmaceuticals, Inc: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Rituximab; Imatinib Mesylate; Cyclophosphamide; Doxorubicin; Mesna; Vincristine; Methylprednisolone Hemisuccinate; Methylprednisolone; Methylprednisolone Acetate; Methotrexate; Cytarabine; Granulocyte Colony-Stimulating Factor; Filgrastim; pegfilgrastim; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Aminopterin; Pterins; Pteridines; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Steroids, Fluorinated; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids

Results Point of Contact

• Title: Elias Joseph Jabbour, MD./ Professor
• Organization: The University of Texas MD Anderson Cancer Center

ejabbour@mdanderson.org

713-792-4764

Study Officials

• Elias Jabbour, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2011
• First Posted: March 22, 2011
• Study Start: March 5, 2013
• Primary Completion: November 11, 2020
• Study Completion: November 11, 2020
• Last Updated: September 27, 2022
• Results First Posted: September 27, 2022

Record last verified: 2022-08

Locations

US (1)