Combination Chemotherapy, Donor Stem Cell Transplant, Tacrolimus, Mycophenolate Mofetil, and Cyclophosphamide in Treating Patients With Hematologic Cancer

NCT00782379 | Completed Phase 2 Results

• 2 other identifiers: CDR0000617648BMTGG-NSH-864
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem 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. Giving high-dose cyclophosphamide together with tacrolimus and mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well combination chemotherapy works when given together with a donor stem cell transplant, followed by tacrolimus, mycophenolate mofetil, and high-dose cyclophosphamide, in treating patients with high-risk hematologic cancer.

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes

Keywords

stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult Hodgkin lymphoma; stage III adult lymphoblastic lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult Hodgkin lymphoma; stage IV adult lymphoblastic lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult Hodgkin lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II mantle cell lymphoma; accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); chronic myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; recurrent adult acute myeloid leukemia; refractory chronic lymphocytic leukemia; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; prolymphocytic leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of Graft Rejection for Patients at Day 100

  Number of patients who experienced graft rejection by Day 100

  Day 100

• Number of Patients Who Experienced Severe Graft-versus-host Disease (GVHD)(Grade 3 or 4)

  Number of patients who experienced post-transplant complication (GVHD) as seen by clinical evidence

  Day 100

Secondary Outcomes (9)

• Overall Survival at Day 100

  Day 100

• Non-relapse Mortality at 1 Year After Peripheral Blood Stem Cell Transplantation (PBSCT)

  1 year

• Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 30 Post-transplantation

  Day 30

• Non-relapse Mortality at Day 100 After Peripheral Blood Stem Cell Transplantation (PBSCT)

  Day 100

• Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 60 Post-transplantation

  Day 60

Study Arms (1)

Myeloablative Haploidentical Transplant

EXPERIMENTAL

All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide.

Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Interventions

busulfan DRUG

110 mg/m2 infused over 3 hours once daily on 4 consecutive days (Days -7, -6, -5, -4)

Myeloablative Haploidentical Transplant

cyclophosphamide DRUG

14.5 mg/kg infused over 1-2 hours once daily on 2 consecutive days (days -3,-2).

Myeloablative Haploidentical Transplant

fludarabine phosphate DRUG

30mg/m2 infused over 30 minutes once daily on three consecutive days (days -5, -4, -3)

Myeloablative Haploidentical Transplant

mycophenolate mofetil DRUG

15 mg/kg po three times a daily with a maximum dose of 3gm/day starting D+5. To be discontinued on Day +35 in the absence of clinically significant GVHD.

Also known as: CellCept

Myeloablative Haploidentical Transplant

tacrolimus DRUG

0.03 mg/kg/day infuse over 24 hours starting on day +5 (adjusted to maintain trough level of 5-15 ng/ml). Switch to oral (twice daily divided dose) on day +21 or when able to tolerate PO. Discontinue on day +180 in the absence of clinically significant GVHD.

Also known as: Prograf, FK-506

Myeloablative Haploidentical Transplant

allogeneic hematopoietic stem cell transplantation PROCEDURE

Patients to received unmanipulated PBSCs on Day 0

Also known as: Allo HSCT

Myeloablative Haploidentical Transplant

peripheral blood stem cell transplantation PROCEDURE

patients to receive unmanipulated PBSCs on day 0

Also known as: allogeneic hematopoietic stem cell transplant

Myeloablative Haploidentical Transplant

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

DISEASE CHARACTERISTICS: * Diagnosis of one of the following high-risk hematologic malignancies: * Chronic myelogenous leukemia meeting one of the following criteria: * Disease in chronic phase and resistant to available tyrosine kinase inhibitors * Disease in accelerated phase * Disease with blast crisis that has entered into a second chronic phase after induction chemotherapy * Acute myelogenous leukemia meeting the following criteria: * Marrow blasts \< 5% but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH * Must meet one of the following criteria: * Disease in second or subsequent complete remission * Primary induction chemotherapy failure with disease subsequently entering complete remission * Disease in first complete remission with poor-risk cytogenetics or arising from preceding hematological disease * Myelodysplastic syndrome meeting at least one of the following criteria: * Treatment-related * Monosomy 7 or complex cytogenetics * International prognostic scoring system score ≥ 1.5 * Chronic myelomonocytic leukemia * Acute lymphocytic leukemia or lymphoblastic lymphoma meeting the following criteria: * Marrow blasts \< 5% but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH * Must meet one of the following criteria: * Disease in second or subsequent complete remission * Acute lymphocytic leukemia with poor-risk karyotype \[e.g., t(9;22) or bcr-abl fusion, t(4;11), or other MLL translocation\] and in first complete remission * Chronic lymphocytic leukemia or prolymphocytic leukemia meeting both of the following criteria: * Previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs * In the opinion of the transplant physician, unlikely to benefit from reduced intensity transplantation due to the presence of one or more high-risk features (i.e., bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy) * Hodgkin or non-Hodgkin lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse disease) meeting the following criteria: * Previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation * In the opinion of the transplant physician, unlikely to benefit from reduced intensity transplantation due to the presence of one or more high-risk features (i.e., bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy) NOTE: A new classification scheme for adult non-Hodgkin lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. * No available matched related or unrelated donor OR a matched related or unrelated donor will not be available in the time frame necessary to perform a transplant * Availability of a first-degree relative (parent, child, sibling) matched at 3/6-5/6 loci (HLA-A, -B, -DR) * Donor must be willing to donate mobilized peripheral blood stem cells * No positive HLA crossmatch in the host-vs-graft direction or high titer donor-specific antibodies PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Bilirubin \< 2 mg/dL (unless due to hemolysis, Gilbert syndrome, or primary malignancy) * Creatinine \< 2 mg/dL OR creatinine clearance ≥ 40 mL/min * Not pregnant * Fertile patients must use effective contraception * LVEF (Left ventriculr ejection fraction) ≥ 45% * FEV\_1 and forced vital capacity ≥ 50% predicted * No HIV positivity * No debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal treatment and follow-up PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No immunosuppressive agents ≤ 24 hours after completion of post-transplant cyclophosphamide (including steroids as antiemetics)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Northside Hospital, Inc.: lead

Study Sites (1)

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Hodgkin Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Leukemia, Myeloid, Accelerated Phase; Congenital Abnormalities; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic

Interventions

Busulfan; Cyclophosphamide; fludarabine phosphate; Mycophenolic Acid; Tacrolimus; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Lymphoma, B-Cell; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myelodysplastic-Myeloproliferative Diseases; Leukemia, B-Cell

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Scott Solomon
• Organization: Blood and Marrow Transplant Group of Georgia

ssolomon@bmtga.com

404-255-1930

Study Officials

• Scott R. Solomon, MD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

• H. Kent Holland, MD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

• Asad Bashey, MD, PhD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

• Lawrence E. Morris, MD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2008
• First Posted: October 31, 2008
• Study Start: October 1, 2008
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2012
• Last Updated: November 21, 2013
• Results First Posted: May 3, 2013

Record last verified: 2013-03

Locations

US (1)