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Intensity Modulated Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients With Relapsed Hematologic Cancers Undergoing a Second Donor Stem Cell Transplant

Primary Purpose

Previously Treated Myelodysplastic Syndrome, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Fludarabine Phosphate

Melphalan

Intensity-Modulated Radiation Therapy

Total Marrow Irradiation

Allogeneic Hematopoietic Stem Cell Transplantation

Peripheral Blood Stem Cell Transplantation

Allogeneic Bone Marrow Transplantation

Tacrolimus

Mycophenolate Mofetil

Laboratory Biomarker Analysis

About this trial

This is an interventional treatment trial for Previously Treated Myelodysplastic Syndrome

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with the following diseases: acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) undergoing second allogeneic (allo)-stem cell transplant (SCT) using the same donor or different donor for disease relapse; patients with other hematologic malignancies, including acute lymphoblastic leukemia (ALL), will be at the discretion of the investigators
Karnofsky performance status of 70 or above
Life expectancy is not severely limited by concomitant illness
Adequate cardiac and pulmonary function; patients with decreased left ventricular ejection fraction (LVEF) =< 40% or diffusion capacity of carbon monoxide (DLCO) =< 50% of predicted will be evaluated by cardiology or pulmonary prior to enrollment on this protocol
Serum creatinine =<1.5 mg/dL or creatinine clearance > 50 ml/min; some patients with minor deviations may be accepted on protocol after discussion with the principal investigator (PI)
Serum bilirubin =< 2.0 mg/dl; some patients with minor deviations may be accepted on protocol after discussion with the PI
Serum glutamic oxaloacetic transaminase (SGPT) < 5 x upper limit of normal; some patients with minor deviations may be accepted on protocol after discussion with the PI
No evidence of chronic active hepatitis or cirrhosis
Human immunodeficiency virus (HIV)-negative
Patient is not pregnant
Patient or guardian able to sign informed consent
DONOR: Since these patients already had first allo-SCT; in the majority time, the same matched donor has been used for second allo-SCT; if the patients have multiple donors, alternative matched (8/8 or 10/10) donor could be used for the second allo-SCT; the donor could be matched related donors or matched unrelated donors from registry
DONOR: If more than one potential volunteer unrelated donor is considered suitable, further selection of the most suitable donor will be prioritized as follows or will follow our institutional guideline from our stem cell transplant standard operating procedure (SOP):
- Age of donor (18-24 > 25-34 > 35-44 > 45+)
- Sex of donor (male > female, nulliparous female > parous, multiparous female)
- Cytomegalovirus (CMV) status, if recipient is CMV seronegative (CMV- > CMV+

Sites / Locations

University of Chicago Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Arm Description

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes daily on days -7 to -3 and melphalan IV on day -2. Patients also undergo IMTMI BID for 2 to 5 days between days -7 to -3. TRANSPLANT: Patients undergo allogeneic PBSCT or BMT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO BID on days -2 to 180 with taper thereafter and mycophenolate mofetil IV every 8 hours or PO on days 0-28 (for matched donors) or days 0-40 (for alternative donors) with taper to day 60.

Outcomes

Primary Outcome Measures

MTD of conditioning regimen defined as any grade III or higher dose-limiting toxicity, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Secondary Outcome Measures

Overall incidence of adverse events, graded according to the NCI CTCAE version 4.0

Transplant related mortality

Time to neutrophil engraftment

Time to platelet engraftment

overall survival (OS)

event-free-survival (EFS)

Full Information

NCT ID

NCT02333162

First Posted

January 5, 2015

Last Updated

April 26, 2023

Sponsor

University of Chicago

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT02333162

Brief Title

Intensity Modulated Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients With Relapsed Hematologic Cancers Undergoing a Second Donor Stem Cell Transplant

Official Title

A Phase I Study of Intensity Modulated Total Marrow Irradiation (IMTMI) in Addition to Fludarabine/Melphalan Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 5, 2014 (Actual)

Primary Completion Date

December 1, 2023 (Anticipated)

Study Completion Date

December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Chicago

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This phase I trial studies the side effects and the best dose of intensity modulated total marrow irradiation (IMTMI) when given together with fludarabine phosphate and melphalan in treating patients with cancers of the blood (hematologic) that have returned after a period of improvement (relapsed) undergoing a second donor stem cell transplant. IMTMI is a type of radiation therapy to the bone marrow that may be less toxic and may also reduce the chances of cancer to return. Giving fludarabine phosphate, melphalan, and IMTMI before a donor stem cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also 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.

Detailed Description

PRIMARY OBJECTIVES: I. The determine the maximum tolerated dose (MTD) of intensity-modulate total marrow irradiation (IMTMI) in combination with fludarabine (fludarabine phosphate)/melphalan as conditioning for second allogeneic stem cell transplantation for patients with hematologic malignancies. SECONDARY OBJECTIVES: I. To determine the overall toxicity and day 100 transplant related mortality after second allogeneic hematopoietic stem cell transplantation conditioned with increasing doses of intensity-modulate total marrow irradiation (IMTMI) in combination with fludarabine/melphalan. II. To determine the time to neutrophil and platelet engraftment after second allogeneic hematopoietic stem cell transplantation conditioned with increasing doses of intensity-modulate total marrow irradiation (IMTMI) in combination with fludarabine/melphalan. III. To determine the overall survival (OS) and event-free-survival (EFS) in patients with hematologic undergoing second allogeneic hematopoietic stem cell transplant (HSCT) after conditioning with fludarabine/melphalan and IMTMI. OUTLINE: This is a dose-escalation study of IMTMI. CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes daily on days -7 to -3 and melphalan IV on day -2. Patients also undergo IMTMI twice daily (BID) for 2 to 5 days between days -7 to -3. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) or bone marrow transplant (BMT) on day 0. GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or orally (PO) BID on days -2 to 180 with taper thereafter and mycophenolate mofetil IV every 8 hours or PO on days 0-28 (for matched donors) or days 0-40 (for alternative donors) with taper to day 60. After completion of treatment, patients are followed up periodically for 1 year and then yearly for 2 years.

6. Conditions and Keywords

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

Previously Treated Myelodysplastic Syndrome, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Hematologic Malignancy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Fludarabine Phosphate

Other Intervention Name(s)

2-F-ara-AMP, Beneflur, SH T 586

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Melphalan

Other Intervention Name(s)

Alkeran

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

Intensity-Modulated Radiation Therapy

Other Intervention Name(s)

IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Intervention Description

Undergo IMTMI

Intervention Type

Radiation

Intervention Name(s)

Total Marrow Irradiation

Intervention Description

Undergo IMTMI

Intervention Type

Procedure

Intervention Name(s)

Allogeneic Hematopoietic Stem Cell Transplantation

Other Intervention Name(s)

HSC, HSCT

Intervention Description

Undergo allogeneic PBSCT

Intervention Type

Procedure

Intervention Name(s)

Peripheral Blood Stem Cell Transplantation

Other Intervention Name(s)

PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Intervention Description

Undergo allogeneic PBSCT

Intervention Type

Procedure

Intervention Name(s)

Allogeneic Bone Marrow Transplantation

Other Intervention Name(s)

Allo BMT, Allogeneic BMT

Intervention Description

Undergo allogeneic BMT

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

Advagraf, FK 506

Intervention Description

Given IV or PO

Intervention Type

Drug

Intervention Name(s)

Mycophenolate Mofetil

Other Intervention Name(s)

Cellcept, MMF

Intervention Description

Given IV or PO

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

Time Frame

Up to 30 days post second allo-SCT

Secondary Outcome Measure Information:

Title

Overall incidence of adverse events, graded according to the NCI CTCAE version 4.0

Time Frame

Up to 2 years

Title

Transplant related mortality

Time Frame

Day 100

Title

Time to neutrophil engraftment

Time Frame

First day in which the ANC is > 500/mm^3 for 3 consecutive days

Title

Time to platelet engraftment

Time Frame

First day the platelet count is > 20,000/mm^3 without transfusion support for 7 consecutive days

Title

overall survival (OS)

Time Frame

Up to 2 years

Title

event-free-survival (EFS)

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with the following diseases: acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) undergoing second allogeneic (allo)-stem cell transplant (SCT) using the same donor or different donor for disease relapse; patients with other hematologic malignancies, including acute lymphoblastic leukemia (ALL), will be at the discretion of the investigators Karnofsky performance status of 70 or above Life expectancy is not severely limited by concomitant illness Adequate cardiac and pulmonary function; patients with decreased left ventricular ejection fraction (LVEF) =< 40% or diffusion capacity of carbon monoxide (DLCO) =< 50% of predicted will be evaluated by cardiology or pulmonary prior to enrollment on this protocol Serum creatinine =<1.5 mg/dL or creatinine clearance > 50 ml/min; some patients with minor deviations may be accepted on protocol after discussion with the principal investigator (PI) Serum bilirubin =< 2.0 mg/dl; some patients with minor deviations may be accepted on protocol after discussion with the PI Serum glutamic oxaloacetic transaminase (SGPT) < 5 x upper limit of normal; some patients with minor deviations may be accepted on protocol after discussion with the PI No evidence of chronic active hepatitis or cirrhosis Human immunodeficiency virus (HIV)-negative Patient is not pregnant Patient or guardian able to sign informed consent DONOR: Since these patients already had first allo-SCT; in the majority time, the same matched donor has been used for second allo-SCT; if the patients have multiple donors, alternative matched (8/8 or 10/10) donor could be used for the second allo-SCT; the donor could be matched related donors or matched unrelated donors from registry DONOR: If more than one potential volunteer unrelated donor is considered suitable, further selection of the most suitable donor will be prioritized as follows or will follow our institutional guideline from our stem cell transplant standard operating procedure (SOP): Age of donor (18-24 > 25-34 > 35-44 > 45+) Sex of donor (male > female, nulliparous female > parous, multiparous female) Cytomegalovirus (CMV) status, if recipient is CMV seronegative (CMV- > CMV+

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hongtao Liu

Organizational Affiliation

University of Chicago Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Chicago Comprehensive Cancer Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hongtao Liu

Phone

773-834-0589

hliu2@medicine.bsd.uchicago.edu

First Name & Middle Initial & Last Name & Degree

Hongtao Liu

12. IPD Sharing Statement

Learn more about this trial

Intensity Modulated Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients With Relapsed Hematologic Cancers Undergoing a Second Donor Stem Cell Transplant

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