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Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Melphalan

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Alkylating Agents

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CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1.

STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.

Undergo allogeneic hematopoietic stem cell transplant

Allogeneic Hematopoietic Stem Cell Transplantation

Fludarabine Phosphate

Laboratory Biomarker Analysis

Melphalan Hydrochloride

Mycophenolate Mofetil

Total-Body Irradiation

Maureen Ross

This phase Ib/2 trial studies how well chemotherapy, total body irradiation, and post-transplant cyclophosphamide work in reducing rates of graft versus host disease in patients with hematologic malignancies undergoing a donor stem cell transplant. Drugs used in the chemotherapy, such as fludarabine phosphate and melphalan hydrochloride, 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. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). Giving cyclophosphamide after the transplant may stop this from happening.

PRIMARY OBJECTIVES:

I. To determine the cumulative incidence of extensive chronic graft versus host disease (GVHD) at 1 year after transplantation utilizing the novel conditioning/GVHD prophylactic regimen for patients undergoing allogeneic hematopoietic cell transplantation, in patients who do not progress before day 100.

SECONDARY OBJECTIVES:

I. To evaluate clinical response, engraftment rate, progression-free survival (PFS) at one year and, overall survival (OS).

II. To determine the cumulative incidence of relapse. III. To evaluate the day 100 transplant-related mortality rate. IV. To determine the cumulative incidence of grade III-IV acute GVHD.

OUTLINE: This is a dose-escalation study of melphalan hydrochloride.

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo total body irradiation (TBI) on day -1.

STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and tacrolimus IV and then orally (PO) once tolerated on days 5-180 with a taper beginning on day 100.

After completion of study treatment, patients are followed up for 12 months and then annually thereafter.

Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

A Phase Ib/2 Trial of Fludarabine/Melphalan/Total Body Irradiation With Post Transplant Cyclophosphamide as Graft Versus Host Disease Prophylaxis in Matched-Related and Matched-Unrelated Allogeneic Hematopoietic Cell Transplantation

Will be analyzed for each stratum. Will examine in a post-hoc analysis potential chronic GVHD rates of response by human leukocyte antigen (HLA) matching status.

Will utilize either straight Kaplan-Meier based estimators or extensions of nonparametric survival models to account for competing risks.

Will be analyzed in a descriptive fashion with means +/- standard deviations or frequency counts. Will examine in a post-hoc analysis potential chronic GVHD rates of response by human leukocyte antigen (HLA) matching status.

Will be analyzed in a descriptive fashion with means +/- standard deviations or frequency counts.

Roswell Park Cancer Institute

Infections

Burkitt Lymphoma

Lymphoma, Non-Hodgkin

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Lymphoma, B-Cell

Childhood Acute Lymphoblastic Leukemia

B-cell Lymphoma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Dexamethasone

Cytarabine

Doxorubicin

Liposomal doxorubicin

Methotrexate

Vincristine

Dexamethasone acetate

BB 1101

Ofatumumab

Ichthammol

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antiviral Agents

Tubulin Modulators

Antimitotic Agents

HIV Protease Inhibitors

Protease Inhibitors

Folinic Acid

Folate

Vitamin B9

COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3.

COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4.

Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months.

Doxorubicin Hydrochloride

Vincristine Sulfate

Elias Jabbour

This phase II trial studies how well combination chemotherapy and ofatumumab work in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, 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. Immunotherapy with ofatumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy together with ofatumumab may be an effective treatment for acute lymphoblastic leukemia or lymphoblastic lymphoma.

PRIMARY OBJECTIVES:

I. To evaluate the clinical efficacy of the combination of hyper-CVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone) + ofatumumab in patients with newly diagnosed acute lymphoblastic leukemia with any level of CD20 expression: event-free survival; overall response rate; overall survival.

SECONDARY OBJECTIVES:

I. To evaluate the safety of this combination.

OUTLINE:

COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide intravenously (IV) over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or orally (PO) once daily (QD) on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3.

COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4.

Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 1 year.

Combination Chemotherapy and Ofatumumab in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Phase II Study of the Hyper - CVAD Regimen in Combination With Ofatumumab as Frontline Therapy for Patients With CD-20 Positive Acute Lymphoblastic Leukemia

Complete Remission is Normalization of the peripheral blood and bone marrow with 5% or less blasts in marrow with a granulocyte count of 1 x 109/L or above and a platelet count of 100x 109/L or above. Complete resolution of all sites of extramedullary disease is required for CR.

Overall Survival is defined as time from date of treatment start until date of death due to any cause or last Follow-up. For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum will be computed. The posterior median time to event and it 95% credible interval will be estimated. Kaplan-Meier method, Log rank test and Cox proportional hazards regression modeling will be utilized to analyze survival at 4 years.

Event Free Survival defined as the time from the start of therapy to time of primary refractory disease, relapse from CR, death from any cause or last follow-up. Kaplan-Meier method will be utilized to analyze event free survival for the 4 year percent alive and in CR.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3.

COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4.

Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months.

Cyclophosphamide: Given IV

Cytarabine: Given IV

Dexamethasone: Given IV or PO

Doxorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Methotrexate: Given IV

Ofatumumab: Given IV

Vincristine Sulfate: Given IV

Treatment (Hyper-CVAD, Ofatumumab)

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Elias Joseph Jabbour, MD/ Professor

Number of Participants With Complete Remission (CR)

4-Year Overall Survival

4-year Event Free Survival

Overall Study

Philadelphia Chromosome

Leukemia, Myeloid, Accelerated Phase

Blast Crisis

Translocation, Genetic

Chromosome Aberrations

Cell Transformation, Neoplastic

Carcinogenesis

Amino Acids

Prednisone

Rituximab

Daunorubicin

Ponatinib

Cortisone

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Ponatinib Hydrochloride

This phase II trial studies the side effects and how well combination chemotherapy and ponatinib hydrochloride work in treating patients with acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, 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. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy and ponatinib hydrochloride may be an effective treatment for acute lymphoblastic leukemia.

PRIMARY OBJECTIVES:

I. To evaluate the clinical efficacy (event-free survival) of an intensive short-term chemotherapy regimen (hyperfractionated cyclophosphamide-vincristine sulfate-Adriamycin \[doxorubicin hydrochloride\]-dexamethasone \[hyper-CVAD\] program) given in combination with the tyrosine kinase inhibitor ponatinib hydrochloride (ponatinib) for Philadelphia (Ph)-positive and/or BCR-ABL-positive acute lymphoblastic leukemia (ALL).

II. To evaluate other clinical efficacy endpoints (overall response rate and survival) and safety of the regimen.

OUTLINE:

ODD CYCLES (1, 3, 5, and 7): Patients receive cyclophosphamide intravenously (IV) over 3 hours every 12 hours on days 1-3, doxorubicin hydrochloride IV continuously over 24 hours on day 4, vincristine sulfate IV over 30 minutes on days 1 and 11, dexamethasone IV over 30 minutes or orally (PO) once daily (QD) on days 1-4 and 11-14, and ponatinib hydrochloride PO QD on days 1-14 of cycle 1 and continuously in cycles 3, 5, and 7. Patients with CD20 expression may also receive rituximab IV on days 1 and 11 of cycle 1 and 3. Treatment repeats every 3-4 weeks for up to 8 cycle in the absence of disease progression or unacceptable toxicity.

EVEN CYCLES (2, 4, 6, and 8): Patients receive methotrexate IV over 24 hours on day 1, ponatinib hydrochloride PO QD continuously, and cytarabine IV over 3 hours every 12 hours on days 2 and 3. Patients with CD20 expression may also receive rituximab IV on days 1 and 8 of cycle 2 and 4. Treatment repeats every 3-4 weeks for up to 8 cycle in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive vincristine sulfate IV on day 1, prednisone PO daily on days 1-5, and ponatinib hydrochloride PO QD on days 1-28. Cycle repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 24 months.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant	NCT03192397	Acute Myeloid L... Adult Acute Lym... Chronic Myeloge... Chronic Myelomo... Graft Versus Ho... Hodgkin Lymphom... Minimal Residua... Myelodysplastic... Myeloproliferat... Non-Hodgkin Lym... Plasma Cell Mye... Severe Aplastic... Waldenstrom Mac...	Allogeneic Hema... Cyclophosphamid... Fludarabine Pho... Laboratory Biom... Melphalan Hydro... Mycophenolate M... Sirolimus Total-Body Irra...	18 Years -	Roswell Park Cancer Institute
Combination Chemotherapy and Ofatumumab in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma	NCT01363128	Acute Lymphobla... Adult Acute Lym... Burkitt Leukemi... Burkitt Lymphom... CD20 Positive Childhood Acute... Lymphoblastic L...	Cyclophosphamid... Cytarabine Dexamethasone Doxorubicin Hyd... Laboratory Biom... Methotrexate Ofatumumab Vincristine Sul...	-	M.D. Anderson Cancer Center
Combination Chemotherapy and Ponatinib Hydrochloride in Treating Patients With Acute Lymphoblastic Leukemia	NCT01424982	Accelerated Pha... Acute Lymphobla... Adult Acute Lym... B Acute Lymphob... Blast Phase Chr... Philadelphia Ch... Untreated Adult...	Cyclophosphamid... Cytarabine Dexamethasone Doxorubicin Doxorubicin Hyd... Laboratory Biom... Methotrexate Ponatinib Ponatinib Hydro... Prednisone Rituximab Vincristine Vincristine Sul...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for adult acute lymphoblastic leukemia in complete remission